Search results for: bone marrow transplantation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 905

Search results for: bone marrow transplantation

845 Changing Left Ventricular Hypertrophy After Kidney Transplantation

Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi

Abstract:

Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.

Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain

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844 Neuron Point-of-Care Stem Cell Therapy: Intrathecal Transplant of Autologous Bone Marrow-Derived Stem Cells in Patients with Cerebral Palsy

Authors: F. Ruiz-Navarro, M. Matzner, G. Kobinia

Abstract:

Background: Cerebral palsy (CP) encompasses the largest group of childhood movement disorders, the patterns and severity varies widely. Today, the management focuses only on a rehabilitation therapy that tries to secure the functions remained and prevents complications. However the treatments are not aimed to cure the disease. Stem cells (SCs) transplant via intrathecal is a new approach to the disease. Method: Our aim was to performed a pilot study under the condition of unproven treatment on clinical practice to assessed the safety and efficacy of Neuron Point-of-care Stem cell Therapy (N-POCST), an ambulatory procedure of autologous bone marrow derived SCs (BM-SCs) harvested from the posterior superior iliac crest undergo an on-site cell separation for intrathecal infusion via lumbar puncture. Results: 82 patients were treated in a period of 28 months, with a follow-up after 6 months. They had a mean age of 6,2 years old and male predominance (65,9%). Our preliminary results show that: A. No patient had any major side effects, B. Only 20% presented mild headache due to LP, C. 53% of the patients had an improvement in spasticity, D. 61% improved the coordination abilities, 23% improved the motor function, 15% improved the speech, 23% reduced the number of convulsive events with the same doses or less doses of anti-convulsive medication and 94% of the patients report a subjective general improvement. Conclusions: These results support previous worldwide publications that described the safety and effectiveness of autologous BM-SCs transplant for patients wit CP.

Keywords: autologous transplant, cerebral palsy, point of care, childhood movement disorders

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843 A Novel Treatment of the Arthritic Hip: A Prospective, Cross-Sectional Study on Changes Following Bone Marrow Concentrate Injection and Arthroscopic Debridement

Authors: A. Drapeaux, S. Aviles, E. Garfoot

Abstract:

Stem cell injections are a promising alternative treatment for hip osteoarthritis. Current literature has focused on short-term outcomes for both knee and hip osteoarthritis; however, there is a significant gap for longitudinal benefits for hip OA and limited firm conclusions due to small sample sizes. The purpose of this prospective study was to determine longitudinal changes in pain, function, and radiographs following bone marrow concentrate injection (BMAC) into the osteoarthritic hip joint. Methods: A prospective, cross-sectional study was conducted over the course of 12 months at an orthopedic practice. The study recruited 15 osteoarthritic pre-surgical hips with mild to moderate osteoarthritic severity who were scheduled to undergo hip arthroscopy. Data was collected at both pre-operative and post-operative time frames. Data collected included: hip radiographs, i-HOT-33 questionnaire data, BMAC autologous volume, and demographics. Questionnaire data was captured using Qualtrics XM software, and participants were sent an anonymous link at the following time frames: pre-operative, 2 weeks, 6 weeks, 12 weeks, 6 months, 12 months, and 24 months. Radiographic changes and BMAC volume were collected and reviewed by an orthopedic surgeon and sent to the primary investigator. Data was exported and analyzed in IBM-SPSS. Results: A total of 15 hips from 15 participants (mean age: 49, gender: 50% males, 50% females, BMI: 29.7) were used in the final analysis. Summative i-HOT 33 mean scores significantly changed between pre-operative status and 2-6 weeks post-operative status (p <.001) and pre-operative status and 3-6 months post-operative status (p <.001). There were no significant changes between other post-operative phases or between pre-operative status and 12 months post-operative. Significant improvements were found between summative i-HOT 33 mean (p<.001), daily pain (p<.001), daily sitting (p=.02), daily distance walked (p =.003), and daily limp (p=0.03) and post-operative status (2-6 weeks). No significant differences between demographic variables (gender, age, tobacco use, or diabetes) and i-HOT 33 summative mean scores. Discussion/Implications: The purpose of this study was to determine longitudinal changes in pain and function following a hip joint bone marrow concentrate injection. Results indicate that participants experience a significant improvement in pain and function between pre-operative and 2-6 weeks and 3-6 months post-injection. Participants also self-reported a significant change in average daily pain with sitting and walking between pre-operation and 2-6 weeks post-operative. This study includes a larger sample size of hip osteoarthritis cases; however, future research is warranted to include random controlled trials with a larger sample size.

Keywords: adult stem cell, orthopedics, osteoarthritis (hip), patient outcome assessment

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842 Investigating the Post-Liver Transplant Complications and Their Management in Children Referred to the Children’s Medical Center

Authors: Hosein Alimadadi, Fatemeh Farahmand, Ali Jafarian, Nasir Fakhar, Mohammad Hassan Sohouli, Neda Raeesi

Abstract:

Backgroundsː Regarding the important role of liver transplantation as the only treatment in many cases of end-stage liver disease in children, the aim of this study is to investigate the complications of liver transplantation and their management in children referred to the Children's Medical Center. Methods: This study is a cross-sectional study on pediatric patients who have undergone liver transplants in the years 2016 to 2021. The indication for liver transplantation in this population was confirmed by a pediatric gastroenterologist, and a liver transplant was performed by a transplant surgeon. Finally, information about the patient before and after the transplantation was collected and recorded. Results: A total of 53 patients participated in this study, including 25 (47.2%) boys and 28 (52.8%) girls. The most common causes of liver transplantation were cholestatic and metabolic diseases. The most common early complication of liver transplantation in children was acute cellular rejection (ACR) and anastomotic biliary stricture. The most common late complication in these patients was an infection which was observed in 56.6% of patients. Among the drug side effects, neurotoxicity (convulsions) was seen more in patients, and 15.1% of the transplanted patients died. Conclusion: In this study, the most common early complication of liver transplantation in children was ACR and biliary stricture, and the most common late complication was infection. Neurotoxicity (convulsions) was the most common side effect of drugs.

Keywords: liver transplantation, complication, infection, survival rate

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841 Identification of the Orthotropic Parameters of Cortical Bone under Nanoindentation

Authors: D. Remache, M. Semaan, C. Baron, M. Pithioux, P. Chabrand, J. M. Rossi, J. L. Milan

Abstract:

A good understanding of the mechanical properties of the bone implies a better understanding of its various diseases, such as osteoporosis. Berkovich nanoindentation tests were performed on the human cortical bone to extract its orthotropic parameters. The nanoindentation experiments were then simulated by the finite element method. Different configurations of interactions between the tip indenter and the bone were simulated. The orthotropic parameters of the material were identified by the inverse method for each configuration. The friction effect on the bone mechanical properties was then discussed. It was found that the inverse method using the finite element method is a very efficient method to predict the mechanical behavior of the bone.

Keywords: mechanical behavior of bone, nanoindentation, finite element analysis, inverse optimization approaches

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840 IgA/λ Plasma Cell Myeloma with λ Light Chain Amyloidosis: A Case Report

Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

Abstract:

Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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839 Cryotopic Macroporous Polymeric Matrices for Regenerative Medicine and Tissue Engineering Applications

Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

Abstract:

Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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838 Pretherapy Initial Dosimetry Results in Prostat Cancer Radionuclide Therapy with Lu-177-PSMA-DOTA-617

Authors: M. Abuqebitah, H. Tanyildizi, N. Yeyin, I. Cavdar, M. Demir, L. Kabasakal

Abstract:

Aim: Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for wide range of cancers. Presently dosimetry is highly required either to plan treatment or to ascertain the absorbed dose delivered to critical organs during treatment. Methods and Materials: The study comprised 7 patients suffered from prostate cancer with progressive disease and candidate to undergo Lu-177-DOTA-617 therapy following to PSMA- PET/CT imaging for all patients. (5.2±0.3 mCi) was intravenously injected. To evaluate bone marrow absorbed dose 2 cc blood samples were withdrawn in short variable times (3, 15, 30, 60, 180 minutes) after injection. Furthermore, whole body scans were performed using scintillation gama camera in 4, 24, 48, and 120 hours after injection and in order to quantify the activity taken up in the body, kidneys , liver, right parotid, and left parotid the geometric mean of anterior and posterior counts were determined through ROI analysis, after that background subtraction and attenuation correction were applied using patients PSMA- PET/CT images taking in a consideration: organ thickness, body thickness, and Hounsfield unites from CT scan. OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. Findings: Absorbed doses of bone marrow, left kidney, right kidney, liver, left parotid, right parotid, total body were 1.28±0.52, 32.36±16.36, 32.7±13.68, 10.35±3.45, 38.67±21.29, 37.55±19.77, 2.25±0.95 (mGy/mCi), respectively. Conclusion: Our first results clarify that Lu-177-DOTA-617 is safe and reliable therapy as there were no complications seen. In the other hand, the observable variation in the absorbed dose of the critical organs among the patients necessitate patient-specific dosimetry approach to save body organs and particularly highly exposed kidneys and parotid gland.

Keywords: Lu-177-PSMA, prostate cancer, radionuclide therapy

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837 Review of Correlation between Tacrolimus Pharmacotherapy and Infection after Organ Transplantation

Authors: Zahra Tolou-Ghamari

Abstract:

Introduction: After allogeneic organ transplantation, in order to lower the rate of rejectiontacrolimus is given. In fact, infection is reported as the most complication of tacrolimus that might be associated with higher susceptibility by its’ long term use. Aim: This study aims to review the association between the occurrence of infections after organ transplantation following the administration of tacrolims. Materials and Methods: Scientific literature on the pharmacotherapy of tacrolimus after organ transplantation and infections were searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Results: In order to prevent acute and chronic rejection, the potent immunosuppressive drug tacrolimus administered as a calcineurin inhibitor after organ transplantation. Its’ most frequent infectious complication is reported as urinary tract infection. Virulent strain of recombinant Literiamonocytogenes, in addition to an increase in bacterial burden in the liver and spleen tissues, was reported in the animal experimental study. The consequence of aggressive events and recipients total area under the cureve exposure to immunosuppressive could be as considered as surrogate markers for individual infection’s risk evaluation. Conclusion: Transplant surgery and duration of hospital stay could determinate the risk of infection during the first month of organ transplantation. Despite administration of antiviral drugs, opportunistic infection such as cytomegalovirus could increase the risk of infection during month 1 to year after transplantation.

Keywords: transplant, infection, tacrolimus, kidney

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836 Characterization of Fish Bone Catalyst for Biodiesel Production

Authors: Sarina Sulaiman, N.Khairudin , P.Jamal, M.Z. Alam, Zaki Zainudin, S. Azmi

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In this study, fish bone waste was used as a new catalyst for biodiesel production. Instead of discarding the fish bone waste, it will be utilized as a source for catalyst that can provide significant benefit to the environment. Also, it can be substitute as a calcium oxide source instead of using eggshell, crab shell and snail shell. The XRD and SEM analysis proved that calcined fish bone contains calcium oxide, calcium phosphate and hydroxyapatite. The catalyst was characterized using Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD).

Keywords: calcinations, fish bone, transesterification, waste catalyst

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835 A Radiographic Survey of Eggshell Powder Effect on Tibial Bone Defect Repair Tested in Dog

Authors: M. Yadegari, M. Nourbakhsh, N. Arbabzadeh

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The skeletal system injuries are of major importance. In addition, it is recommended to use materials for hard tissue repair in open or closed fractures. It is important to use complex minerals with a beneficial effect on hard tissue repair, stimulating cell growth in the bone. Materials that could help avoid bone fracture inflammatory reaction and speed up bone fracture repair are of utmost importance in the treatment of bone fractures. Similar to minerals, the inner eggshell membrane consists of carbohydrates, lipids, proteins with the high pH, high calcium absorptive capacity and with faster bone fracture repair ability. In the present radiographic survey, eggshell-derived bone graft substitutes were used for bone defect repair in 8 dog tibia, measuring bone density on the day of implant placement and 30 and 60 days after placement. In fact, the result of this study shows the difference in bone growth and misshapen bones between treatment and control sites. Cell growth was adequate in treatment sites and misshapen bones were less frequent here than in control sites.

Keywords: bone repair, eggshell powder, implant, radiography

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834 Expression of Ki-67 in Multiple Myeloma: A Clinicopathological Study

Authors: Kangana Sengar, Sanjay Deb, Ramesh Dawar

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Introduction: Ki-67 can be a useful marker in determining proliferative activity in patients with multiple myeloma (MM). However, using Ki-67 alone results in the erroneous inclusion of non-myeloma cells leading to false high counts. We have used Dual IHC (immunohistochemistry) staining with Ki-67 and CD138 to enhance specificity in assessing proliferative activity of bone marrow plasma cells. Aims and objectives: To estimate the proportion of proliferating (Ki-67 expressing) plasma cells in patients with MM and correlation of Ki-67 with other known prognostic parameters. Materials and Methods: Fifty FFPE (formalin fixed paraffin embedded) blocks of trephine biopsies of cases diagnosed as MM from 2010 to 2015 are subjected to H & E staining and Dual IHC staining for CD 138 and Ki-67. H & E staining is done to evaluate various histological parameters like percentage of plasma cells, pattern of infiltration (nodular, interstitial, mixed and diffuse), routine parameters of marrow cellularity and hematopoiesis. Clinical data is collected from patient records from Medical Record Department. Each of CD138 expressing cells (cytoplasmic, red) are scored as proliferating plasma cells (containing a brown Ki¬67 nucleus) or non¬proliferating plasma cells (containing a blue, counter-stained, Ki-¬67 negative nucleus). Ki-67 is measured as percentage positivity with a maximum score of hundred percent and lowest of zero percent. The intensity of staining is not relevant. Results: Statistically significant correlation of Ki-67 in D-S Stage (Durie & Salmon Stage) I vs. III (p=0.026) and ISS (International Staging System) Stage I vs. III (p=0.019), β2m (p=0.029) and percentage of plasma cells (p < 0.001) is seen. No statistically significant correlation is seen between Ki-67 and hemoglobin, platelet count, total leukocyte count, total protein, albumin, S. calcium, S. creatinine, S. LDH, blood urea and pattern of infiltration. Conclusion: Ki-67 index correlated with other known prognostic parameters. However, it is not determined routinely in patients with MM due to little information available regarding its relevance and paucity of studies done to correlate with other known prognostic factors in MM patients. To the best of our knowledge, this is the first study in India using Dual IHC staining for Ki-67 and CD138 in MM patients. Routine determination of Ki-67 will help to identify patients who may benefit with more aggressive therapy. Recommendation: In this study follow up of patients is not included, and the sample size is small. Studying with larger sample size and long follow up is advocated to prognosticate Ki-67 as a marker of survival in patients with multiple myeloma.

Keywords: bone marrow, dual IHC, Ki-67, multiple myeloma

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833 Ultrasonic Densitometry of Bone Tissue of Jaws and Phalanges of Fingers in Patients after Orthodontic Treatment

Authors: Margarita Belousova

Abstract:

The ultrasonic densitometry (RU patent № 2541038) was used to assess the density of the bone tissue in the jaws of patients after orthodontic treatment. In addition, by ultrasonic densitometry assessed the state of the bone tissue in the region III phalanges of middle fingers in above mentioned patients. A comparative study was carried out in healthy volunteers of same age. It was established a significant decrease of the ultrasound wave speed and bone mineral density after active period of orthodontic treatment. Statistically, significant differences in bone mineral density of the fingers by ultrasonic densitometry in both groups of patients were not detected.

Keywords: intraoral ultrasonic densitometry, bone tissue density of jaws, bone tissue density of phalanges of fingers, orthodontic treatment

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832 Viscoelastic Characterization of Bovine Trabecular Bone Samples

Authors: I. Ramirez D. Edgar, J. Angeles H. José, Ruiz C. Osvaldo, H. Jacobo A. Victor, Ortiz P. Armando

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Knowledge of bone mechanical properties is important for bone substitutes design and fabrication, and more efficient prostheses development. The aim of this study is to characterize the viscoelastic behavior of bone specimens, through stress relaxation and fatigue tests performed to trabecular bone samples from bovine femoral heads. Relaxation tests consisted on preloading the samples at five different magnitudes and evaluate them for 1020 seconds, adjusting the results to a KWW mathematical model. Fatigue tests consisted of 700 load cycles and analyze their status at the end of the tests. As a conclusion we have that between relaxation stress and each preload there is linear relation and for samples with initial Young´s modulus greater than 1.5 GPa showed no effects due fatigue test loading cycles.

Keywords: bone viscoelasticity, fatigue test, stress relaxation test, trabecular bone properties

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831 Biological Optimization following BM-MSC Seeding of Partially Demineralized and Partially Demineralized Laser-Perforated Structural Bone Allografts Implanted in Critical Femoral Defects

Authors: S. AliReza Mirghasemi, Zameer Hussain, Mohammad Saleh Sadeghi, Narges Rahimi Gabaran, Mohamadreza Baghaban Eslaminejad

Abstract:

Background: Despite promising results have shown by osteogenic cell-based demineralized bone matrix composites, they need to be optimized for grafts that act as structural frameworks in load-bearing defects. The purpose of this experiment is to determine the effect of bone-marrow-mesenchymal-stem-cells seeding on partially demineralized laser-perforated structural allografts that have been implanted in critical femoral defects. Materials and Methods: P3 stem cells were used for graft seeding. Laser perforation in four rows of three holes was achieved. Cell-seeded grafts were incubated for one hour until they were planted into the defect. We used four types of grafts: partially demineralized only (Donly), partially demineralized stem cell seeded (DST), partially demineralized laser-perforated (DLP), and partially demineralized laser-perforated stem cell seeded (DLPST). histologic and histomorphometric analysis were performed at 12 weeks. Results: Partially demineralized laser-perforated had the highest woven bone formation within graft limits, stem cell seeded demineralized laser-perforated remained intact, and the difference between partially demineralized only and partially demineralized stem cell seeded was insignificant. At interface, partially demineralized laser-perforated and partially demineralized only had comparable osteogenesis, but partially demineralized stem cell seeded was inferior. The interface in stem cell seeded demineralized laser-perforated was almost replaced by distinct endochondral osteogenesis with higher angiogenesis in the vicinity. Partially demineralized stem cell seeded and stem cell seeded demineralized laser-perforated graft surfaces had extra vessel-ingrowth-like porosities, a sign of delayed resorption. Conclusion: This demonstrates that simple cell-based composites are not optimal and necessitates the supplementation of synergistic stipulations and surface changes.

Keywords: structural bone allograft, partial demineralization, laser perforation, mesenchymal stem cell

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830 Treatment of Neuronal Defects by Bone Marrow Stem Cells Differentiation to Neuronal Cells Cultured on Gelatin-PLGA Scaffolds Coated with Nano-Particles

Authors: Alireza Shams, Ali Zamanian, Atefehe Shamosi, Farnaz Ghorbani

Abstract:

Introduction: Although the application of a new strategy remains a remarkable challenge for treatment of disabilities due to neuronal defects, progress in Nanomedicine and tissue engineering, suggesting the new medical methods. One of the promising strategies for reconstruction and regeneration of nervous tissue is replacing of lost or damaged cells by specific scaffolds after Compressive, ischemic and traumatic injuries of central nervous system. Furthermore, ultrastructure, composition, and arrangement of tissue scaffolds are effective on cell grafts. We followed implantation and differentiation of mesenchyme stem cells to neural cells on Gelatin Polylactic-co-glycolic acid (PLGA) scaffolds coated with iron nanoparticles. The aim of this study was to evaluate the capability of stem cells to differentiate into motor neuron-like cells under topographical cues and morphogenic factors. Methods and Materials: Bone marrow mesenchymal stem cells (BMMSCs) was obtained by primary cell culturing of adult rat bone marrow got from femur bone by flushing method. BMMSCs were incubated with DMEM/F12 (Gibco), 15% FBS and 100 U/ml pen/strep as media. Then, BMMSCs seeded on Gel/PLGA scaffolds and tissue culture (TCP) polystyrene embedded and incorporated by Fe Nano particles (FeNPs) (Fe3o4 oxide (M w= 270.30 gr/mol.). For neuronal differentiation, 2×10 5 BMMSCs were seeded on Gel/PLGA/FeNPs scaffolds was cultured for 7 days and 0.5 µ mol. Retinoic acid, 100 µ mol. Ascorbic acid,10 ng/ml. Basic fibroblast growth factor (Sigma, USA), 250 μM Iso butyl methyl xanthine, 100 μM 2-mercaptoethanol, and 0.2 % B27 (Invitrogen, USA) added to media. Proliferation of BMMSCs was assessed by using MTT assay for cell survival. The morphology of BMMSCs and scaffolds was investigated by scanning electron microscopy analysis. Expression of neuron-specific markers was studied by immunohistochemistry method. Data were analyzed by analysis of variance, and statistical significance was determined by Turkey’s test. Results: Our results revealed that differentiation and survival of BMMSCs into motor neuron-like cells on Gel/PLGA/FeNPs as a biocompatible and biodegradable scaffolds were better than those cultured in Gel/PLGA in absence of FeNPs and TCP scaffolds. FeNPs had raised physical power but decreased capacity absorption of scaffolds. Well defined oriented pores in scaffolds due to FeNPs may activate differentiation and synchronized cells as a mechanoreceptor. Induction effects of magnetic FeNPs by One way flow of channels in scaffolds help to lead the cells and can facilitate direction of their growth processes. Discussion: Progression of biological properties of BMMSCs and the effects of FeNPs spreading under magnetic field was evaluated in this investigation. In vitro study showed that the Gel/PLGA/FeNPs scaffold provided a suitable structure for motor neuron-like cells differentiation. This could be a promising candidate for enhancing repair and regeneration in neural defects. Dynamic and static magnetic field for inducing and construction of cells can provide better results for further experimental studies.

Keywords: differentiation, mesenchymal stem cells, nano particles, neuronal defects, Scaffolds

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829 Epidemiology of Bone Hydatidosis in Eastern Libya from 1995 to 2013

Authors: Sadek A. Makhlouf, Hassan M. Nouh

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Bone hydatidosis is an infection in worldwide distribution. Although there is no evidence in literature on Bone Hydatid disease in Libya, we tried to present the first epidemiological study of this disease in Eastern Libya through retrospective study from 1995 to 2013. Our data were collected from 3 hospitals in Eastern Libya particularly the sheep-raising areas with total number of musculoskeletal infection cases of two thousand one hundred ninety-four (2,194). There were five (5) five cases of bone infection, four (4) of it have been diagnosed after more than three (3) months. Our study is comparable to other international study but this type of bone infection need further studies for effective control strategies for all dogs to avoid serious complications that might happened from the delay in diagnosing this type of disease.

Keywords: bone infection, hydatidosis, Eastern Libya, sheep-raising areas

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828 Breast Cancer Mortality and Comorbidities in Portugal: A Predictive Model Built with Real World Data

Authors: Cecília M. Antão, Paulo Jorge Nogueira

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Breast cancer (BC) is the first cause of cancer mortality among Portuguese women. This retrospective observational study aimed at identifying comorbidities associated with BC female patients admitted to Portuguese public hospitals (2010-2018), investigating the effect of comorbidities on BC mortality rate, and building a predictive model using logistic regression. Results showed that the BC mortality in Portugal decreased in this period and reached 4.37% in 2018. Adjusted odds ratio indicated that secondary malignant neoplasms of liver, of bone and bone marrow, congestive heart failure, and diabetes were associated with an increased chance of dying from breast cancer. Although the Lisbon district (the most populated area) accounted for the largest percentage of BC patients, the logistic regression model showed that, besides patient’s age, being resident in Bragança, Castelo Branco, or Porto districts was directly associated with an increase of the mortality rate.

Keywords: breast cancer, comorbidities, logistic regression, adjusted odds ratio

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827 Hydroxyapatite Based Porous Scaffold for Tooth Tissue Engineering

Authors: Pakize Neslihan Taslı, Alev Cumbul, Gul Merve Yalcın, Fikrettin Sahin

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A key experimental trial in the regeneration of large oral and craniofacial defects is the neogenesis of osseous and ligamentous interfacial structures. Currently, oral regenerative medicine strategies are unpredictable for repair of tooth supporting tissues destroyed as a consequence of trauma, chronic infection or surgical resection. A different approach combining the gel-casting method with Hydroxy Apatite HA-based scaffold and different cell lineages as a hybrid system leads to successively mimic the early stage of tooth development, in vitro. HA is widely accepted as a bioactive material for guided bone and tooth regeneration. In this study, it was reported that, HA porous scaffold preparation, characterization and evaluation of structural and chemical properties. HA is the main factor that exists in tooth and it is in harmony with structural, biological, and mechanical characteristics. Here, this study shows mimicking immature tooth at the late bell stage design and construction of HA scaffolds for cell transplantation of human Adipose Stem Cells (hASCs), human Bone Marrow Stem Cells (hBMSCs) and Gingival Epitelial cells for the formation of human tooth dentin-pulp-enamel complexes in vitro. Scaffold characterization was demonstrated by SEM, FTIR and pore size and density measurements. The biological contraction of dental tissues against each other was demonstrated by mRNA gene expressions, histopatologic observations and protein release profile by ELISA tecnique. The tooth shaped constructs with a pore size ranging from 150 to 300 µm arranged by gathering right amounts of materials provide interconnected macro-porous structure. The newly formed tissue like structures that grow and integrate within the HA designed constructs forming tooth cementum like tissue, pulp and bone structures. These findings are important as they emphasize the potential biological effect of the hybrid scaffold system. In conclusion, this in vitro study clearly demonstrates that designed 3D scaffolds shaped as a immature tooth at the late bell stage were essential to form enamel-dentin-pulp interfaces with an appropriate cell and biodegradable material combination. The biomimetic architecture achieved here is providing a promising platform for dental tissue engineering.

Keywords: tooth regeneration, tissue engineering, adipose stem cells, hydroxyapatite tooth engineering, porous scaffold

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826 Plasma Treatment in Conjunction with EGM-2 Medium Can Enhance Endothelial and Osteogenic Marker Expressions of Bone Marrow MSCs

Authors: Chih-Hsin Lin, Shyh-Yuan Lee, Yuan-Min Lin

Abstract:

For many tissue engineering applications, an important goal is to create functional tissues in-vitro, and such tissues to be viable, they have to be vascularized. Endothelial cells (EC) and endothelial progenitor cells (EPC) are promising candidates for vascularization. However, both of them have limited expansion capacity and autologous cells currently do not exist for either ECs or EPCs. Therefore, we use bone marrow mesenchymal stem cells (MSC) as a source material for ECs. Growth supplements are commonly used to induce MSC differentiation, and further improvements in differentiation conditions can be made by modifying the cell's growth environment. An example is pre-treatment of the growth dish with gas plasma, in order to modify the surface functional groups of the material that the cells are seeded on. In this work, we compare the effects of different gas plasmas on the growth and differentiation of MSCs. We treat the dish with different plasmas (CO2, N2, and O2) and then induce MSC differentiation with endothelial growth medium-2 (EGM-2). We find that EGM-2 by itself upregulates EC marker CD31 mRNA expression, but not VEGFR2, CD34, or vWF. However, these additional EC marker expressions were increased for cells seeded on plasma treated substrates. Specifically, for EC markers, we found that N2 plasma treatment upregulated CD31 and VEGFR-2 mRNA expressions; CO2 plasma treatment upregulated CD34 and vWF mRNA expressions. The osteogenic markers ALP and osteopontin mRNA expressions were markedly enhanced on all plasma-treated dishes. We also found that plasma treatment in conjunction with EGM-2 growth medium can enhance MSCs differentiation into endothelial-like cells and osteogenic-like cells. Our work shows that the effect of the growth medium (EGM-2) on MSCs differentiation is influenced by the plasma modified surface chemistry of the substrate. In conclusion, plasma surface modification can enhance EGM-2 effectiveness and induced both endothelial and osteogenic differentiation. Our findings provide a method to enhance EGM-2 based cell differentiation, with consequences for tissue engineering and stem cell biology applications.

Keywords: endothelial differentiation, EGM-2, osteogenesis, plasma treatment, surface modification

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825 Experimental Research of Canine Mandibular Defect Construction with the Controlled Meshy Titanium Alloy Scaffold Fabricated by Electron Beam Melting Combined with BMSCs-Encapsulating Chitosan Hydrogel

Authors: Wang Hong, Liu Chang Kui, Zhao Bing Jing, Hu Min

Abstract:

Objection We observed the repairment effection of canine mandibular defect with meshy Ti6Al4V scaffold fabricated by electron beam melting (EBM) combined with bone marrow mesenchymal stem cells (BMMSCs) encapsulated in chitosan hydrogel. Method Meshy titanium scaffolds were prepared by EBM of commercial Ti6Al4V power. The length of scaffolds was 24 mm, the width was 5 mm and height was 8mm. The pore size and porosity were evaluated by scanning electron microscopy (SEM). Chitosan /Bio-Oss hydrogel was prepared by chitosan, β- sodium glycerophosphate and Bio-Oss power. BMMSCs were harvested from canine iliac crests. BMMSCs were seeded in titanium scaffolds and encapsulated in Chitosan /Bio-Oss hydrogel. The validity of BMMSCs was evaluated by cell count kit-8 (CCK-8). The osteogenic differentiation ability was evaluated by alkaline phosphatase (ALP) activity and gene expression of OC, OPN and CoⅠ. Combination were performed by injecting BMMSCs/ Chitosan /Bio-Oss hydrogel into the meshy Ti6Al4V scaffolds and solidified. 24 mm long box-shaped bone defects were made at the mid-portion of mandible of adult beagles. The defects were randomly filled with BMMSCs/ Chitosan/Bio-Oss + titanium, Chitosan /Bio-Oss+titanium, titanium alone. Autogenous iliac crests graft as control group in 3 beagles. Radionuclide bone imaging was used to monitor the new bone tissue at 2, 4, 8 and 12 weeks after surgery. CT examination was made on the surgery day and 4 weeks, 12 weeks and 24 weeks after surgery. The animals were sacrificed in 4, 12 and 24 weeks after surgery. The bone formation were evaluated by histology and micro-CT. Results: The pores of the scaffolds was interconnected, the pore size was about 1 mm, the average porosity was about 76%. The pore size of the hydrogel was 50-200μm and the average porosity was approximately 90%. The hydrogel were solidified under the condition of 37℃in 10 minutes. The validity and the osteogenic differentiation ability of BMSCs were not affected by titanium scaffolds and hydrogel. Radionuclide bone imaging shown an increasing tendency of the revascularization and bone regeneration was observed in all the groups at 2, 4, 8 weeks after operation, and there were no changes at 12weeks.The tendency was more obvious in the BMMSCs/ Chitosan/Bio-Oss +titanium group and autogenous group. CT, Micro-CT and histology shown that new bone formed increasingly with the time extend. There were more new bone regenerated in BMMSCs/ Chitosan /Bio-Oss + titanium group and autogenous group than the other two groups. At 24 weeks, the autogenous group was achieved bone union. The BMSCs/ Chitosan /Bio-Oss group was seen extensive new bone formed around the scaffolds and more new bone inside of the central pores of scaffolds than Chitosan /Bio-Oss + titanium group and titanium group. The difference was significantly. Conclusion: The titanium scaffolds fabricated by EBM had controlled porous structure, good bone conduction and biocompatibility. Chitosan /Bio-Oss hydrogel had injectable plasticity, thermosensitive property and good biocompatibility. The meshy Ti6Al4V scaffold produced by EBM combined BMSCs encapsulated in chitosan hydrogel had good capacity on mandibular bone defect repair.

Keywords: mandibular reconstruction, tissue engineering, electron beam melting, titanium alloy

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824 A Comparison of Implant Stability between Implant Placed without Bone Graft versus with Bone Graft Using Guided Bone Regeneration (GBR) Technique: A Resonance Frequency Analysis

Authors: R. Janyaphadungpong, A. Pimkhaokham

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This prospective clinical study determined the insertion torque (IT) value and monitored the changes in implant stability quotient (ISQ) values during the 12 weeks healing period from implant placement without bone graft (control group) and with bone graft using the guided bone regeneration (GBR) technique (study group). The relationship between the IT and ISQ values of the implants was also assessed. The control and study groups each consisted of 6 patients with 8 implants per group. The ASTRA TECH Implant System™ EV 4.2 mm in diameter was placed in the posterior mandibular region. In the control group, implants were placed in bone without bone graft, whereas in the study group implants were placed simultaneously with the GBR technique at favorable bone defect. IT (Ncm) of each implant was recorded when fully inserted. ISQ values were obtained from the Osstell® ISQ at the time of implant placement, and at 2, 4, 8, and 12 weeks. No difference in IT was found between groups (P = 0.320). The ISQ values in the control group were significantly higher than in the study group at the time of implant placement and at 4 weeks. There was no significant association between IT and ISQ values either at baseline or after the 12 weeks. At 12 weeks of healing, the control and study groups displayed different trends. Mean ISQ values for the control group decreased over the first 2 weeks and then started to increase. ISQ value increases were statistically significant at 8 weeks and later, whereas mean ISQ values in the study group decreased over the first 4 weeks and then started to increase, with statistical significance after 12 weeks. At 12 weeks, all implants achieved osseointegration with mean ISQ values over the threshold value (ISQ>70). These results indicated that implants, in which guided bone regeneration technique was performed during implant placement for treating favorable bone defects, were as predictable as implants placed without bone graft. However, loading in implants placed with the GBR technique for correcting favorable bone defects should be performed after 12 weeks of healing to ensure implant stability and osseointegration.

Keywords: dental implant, favorable bone defect, guided bone regeneration technique, implant stability

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823 Mechanical Cortical Bone Characterization with the Finite Element Method Based Inverse Method

Authors: Djamel Remache, Marie Semaan, Cécile Baron, Martine Pithioux, Patrick Chabrand, Jean-Marie Rossi, Jean-Louis Milan

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Cortical bone is a complex multi-scale structure. Even though several works have contributed significantly to understanding its mechanical behavior, this behavior remains poorly understood. Nanoindentation testing is one of the primary testing techniques for the mechanical characterization of bone at small scales. The purpose of this study was to provide new nanoindentation data of cortical bovine bone in different directions and at different bone microstructures (osteonal, interstitial and laminar bone), and then to identify anisotropic properties of samples with FEM (finite element method) based inverse method. Experimentally and numerical results were compared. Experimental and numerical results were compared. The results compared were in good agreement.

Keywords: mechanical behavior of bone, nanoindentation, finite element analysis, inverse optimization approach

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822 Collagen Gel in Hip Cartilage Repair: in vivo Preliminary Study

Authors: A. Bajek, J. Skopinska-Wisniewska, A. Rynkiewicz, A. Jundzill, M. Bodnar, A. Marszalek, T. Drewa

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Traumatic injury and age-related degenerative diseases associated with cartilage are major health problems worldwide. The articular cartilage is comprised of a relatively small number of cells, which have a relatively slow rate of turnover. Therefore, damaged articular cartilage has a limited capacity for self-repair. New clinical methods have been designed to achieve better repair of injured cartilage. However, there is no treatment that enables full restoration of it. The aim of this study was to evaluate how collagen gel with bone marrow mesenchymal stem cells (MSCs) and collagen gel alone will influence on the hip cartilage repair after injury. Collagen type I was isolated from rats’ tails and cross-linked with N-hydroxysuccinimide in 24-hour process. MSCs were isolated from rats’ bone marrow. The experiments were conducted according to the guidelines for animal experiments of Ethics Committee. Fifteen 8-week-old Wistar rats were used in this study. All animals received hip joint surgery with a total of 30 created cartilage defects. Then, animals were randomly divided into three groups and filled, respectively, with collagen gel (group 1), collagen gel cultured with MSCs (group II) or left untreated as a control (control group). Immunohistochemy and radiological evaluation was carried out 11 weeks post implantation. It has been proved that the surface of the matrix is non-toxic, and its porosity promotes cell adhesion and growth. However, the in vivo regeneration process was poor. We observed the low integration rate of biomaterial. Immunohistochemical evaluation of cartilage after 11 weeks of treatment showed low II and high X collagen expression in two tested groups in comparison to the control one, in which we observed the high II collagen expression. What is more, after radiological analysis, we observed the best regeneration process in control group. The biomaterial construct and mesenchymal stem cells, as well as the use of the biomaterial itself was not sufficient to regenerate the hip cartilage surfaces. These results suggest that the collagen gel based biomaterials, even with MSCs, are not satisfactory in repar of hip cartilage defect. However, additional evaluation is needed to confirm these results.

Keywords: collafen gel, MSCs, cartilage repair, hip cartilage

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821 Relation between Initial Stability of the Dental Implant and Bone-Implant Contact Level

Authors: Jui-Ting Hsu, Heng-Li Huang, Ming-Tzu Tsai, Kuo-Chih Su, Lih-Jyh Fuh

Abstract:

The objectives of this study were to measure the initial stability of the dental implant (ISQ and PTV) in the artificial foam bone block with three different quality levels. In addition, the 3D bone to implant contact percentage (BIC%) was measured based on the micro-computed tomography images. Furthermore, the relation between the initial stability of dental implant (ISQ and PTV) and BIC% were calculated. The experimental results indicated that enhanced the material property of the artificial foam bone increased the initial stability of the dental implant. The Pearson’s correlation coefficient between the BIC% and the two approaches (ISQ and PTV) were 0.652 and 0.745.

Keywords: dental implant, implant stability quotient, peak insertion torque, bone-implant contact, micro-computed tomography

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820 Alteration of Bone Strength in Osteoporosis of Mouse Femora: Computational Study Based on Micro CT Images

Authors: Changsoo Chon, Sangkuy Han, Donghyun Seo, Jihyung Park, Bokku Kang, Hansung Kim, Keyoungjin Chun, Cheolwoong Ko

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The purpose of the study is to develop a finite element model based on 3D bone structural images of Micro-CT and to analyze the stress distribution for the osteoporosis mouse femora. In this study, results of finite element analysis show that the early osteoporosis of mouse model decreased a bone density in trabecular region; however, the bone density in cortical region increased.

Keywords: micro-CT, finite element analysis, osteoporosis, bone strength

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819 Preparation and Characterization of Activated Carbon from Animal Bone

Authors: Getenet Aseged Zeleke

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The aim of this project was to study the synthesis of activated carbon from low-cost animal beef and the characterization of the product obtained. The bone was carbonized in an inert atmosphere at three different temperatures (500°C, 700oC and 900°C) in an electric furnace, followed by activation with hydrochloric acid. The activated animal bone charcoals obtained were characterized by using scanning electron microscopy (SEM)to observe the effect of activation compared to the unactivated bone charcoal. The following parameters were also determined: ash content, moisture content, volatile content, fixed carbon, pH, pore volume and bulk (apparent) density. The characterization result showed that the activated bone charcoal has good properties and is compared favorably with other reference activated carbons.

Keywords: bones, carbonization, activation, characterization, activated carbon

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818 Reconstructing Calvarial Bone Lesions Using PHBV Scaffolds and Cord Blood Mesenchymal Stem Cells in Rat

Authors: Hamed Hosseinkazemi, Esmaeil Biazar

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For tissue engineering of bone, anatomical and operational reconstructions of damaged tissue seem to be vital. This is done via reconstruction of bone and appropriate biological joint with bone tissues of damaged areas. In this study the condition of biodegradable bed Nanofibrous PHBV and USSC cells were used to accelerate bone repair of damaged area. Hollow nanofabrication scaffold of damageable life was designed as PHBV by electrospinning and via determining the best factors such as the kind and amount of solvent, specific volume and rate. The separation of osseous tissue infiltration and evaluating its nature by flow cytometrocical analysis was done. Animal test including USSC as well as PHBV condition in the damaged bone was done in the rat. After 8 weeks the implanted area was analyzed using CT scan and was sent to histopathology ward. Finally, the rate and quality of reconstruction were determined after H and E coloring. Histomorphic analysis indicated a statistically significant difference between the experimental group of PHBV, USSC+PHBV and control group. Besides, the histopathologic analysis showed that bone reconstruction rate was high in the area containing USSC and PHBV, compared with area having PHBV and control group and consequently the reconstruction quality of bones and the relationship between the new bone tissues and surrounding bone tissues were high too. Using PHBR scaffold and USSC together could be useful in the amending of wide range of bone lesion.

Keywords: bone lesion, nanofibrous PHBV, stem cells, umbilical cord blood

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817 Stress-Strain Relation for Human Trabecular Bone Based on Nanoindentation Measurements

Authors: Marek Pawlikowski, Krzysztof Jankowski, Konstanty Skalski, Anna Makuch

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Nanoindentation or depth-sensing indentation (DSI) technique has proven to be very useful to measure mechanical properties of various tissues at a micro-scale. Bone tissue, both trabecular and cortical one, is one of the most commonly tested tissues by means of DSI. Most often such tests on bone samples are carried out to compare the mechanical properties of lamellar and interlamellar bone, osteonal bone as well as compact and cancellous bone. In the paper, a relation between stress and strain for human trabecular bone is presented. The relation is based on the results of nanoindentation tests. The formulation of a constitutive model for human trabecular bone is based on nanoindentation tests. In the study, the approach proposed by Olivier-Pharr is adapted. The tests were carried out on samples of trabecular tissue extracted from human femoral heads. The heads were harvested during surgeries of artificial hip joint implantation. Before samples preparation, the heads were kept in 95% alcohol in temperature 4 Celsius degrees. The cubic samples cut out of the heads were stored in the same conditions. The dimensions of the specimens were 25 mm x 25 mm x 20 mm. The number of 20 samples have been tested. The age range of donors was between 56 and 83 years old. The tests were conducted with the indenter spherical tip of the diameter 0.200 mm. The maximum load was P = 500 mN and the loading rate 500 mN/min. The data obtained from the DSI tests allows one only to determine bone behoviour in terms of nanoindentation force vs. nanoindentation depth. However, it is more interesting and useful to know the characteristics of trabecular bone in the stress-strain domain. This allows one to simulate trabecular bone behaviour in a more realistic way. The stress-strain curves obtained in the study show relation between the age and the mechanical behaviour of trabecular bone. It was also observed that the bone matrix of trabecular tissue indicates an ability of energy absorption.

Keywords: constitutive model, mechanical behaviour, nanoindentation, trabecular bone

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816 Effect of Nicorandil, Bone Marrow-Derived Mesenchymal Stem Cells and Their Combination in Isoproterenol-Induced Heart Failure in Rats

Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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