Search results for: mesenchymal

Authors: Prabhu Thangaraju, Manoj Deepak, A. Sivakumar

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Removal of inter vertebral disc along with spinal fusion has many disadvantages such as causing stress fractures. If it is possible regenerate the spine it would be possible avoid the complications of the surgery and achieve better results. Our study involves the use of mesenchymal stem cells in regenerating the discs. Our study involved 10 patients who presented with degenerative disc disease between 2008-2011 in our hospital. After adequate pre-operative check prepared mesenchymal stem cells were injected into the disc spaces. These patients were subjected to conservative therapy for a minimum of six weeks before they were accepted into the study. They were followed up regularly for a minimum of 2years with serial radiographs and MRI. 8 out of the 10 patients had completed reduction in the pain. The T2 weighted MRI images in 9 out of the 10 patients showed a bright signal compared the previous Images which indicated that there was improvement in the hydration levels. From the case study of 10 patients who were subjected to mesenchymal cell therapy in our hospital, we can conclude that the use of mesenchymal cells in treatment of intervertebral disc degeneration in a safe and effective option.

Keywords: mesenchymal stem cells, intervertebral disc, the spine, disc degeneration

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Authors: K. Barbaro, F. Di Egidio, A. Amaddeo, G. Lupoli, S. Eramo, G. Barraco, D. Amaddeo, C. Gallottini

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In this study, we wanted to evaluate the effects of nano-hydroxy apatite (NHA) on mesenchymal stem cells extracted from subcutaneous adipose tissue of the dog. The stem cells were divided into 6 experimental groups at different concentrations of NHA. The comparison was made with a control group of stem cell grown in standard conditions without NHA. After 1 week, the cells were fixed with 10% buffered formalin for 1 hour at room temperature and stained with Giemsa, measured at the inverted optical microscope. The morphological evaluation of the control samples and those treated showed that stem cells adhere to the substrate and proliferate in the presence of nanohydroxy apatite at different concentrations showing no detectable toxic effects.

Keywords: nano-hydroxy apatite, adipose mesenchymal stem cells, dog, morphological evaluation

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Authors: Lina Liang, Kai Xu, Jing Zhang

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Purpose: Age-related macular degeneration (AMD) is a major leading cause of visual impairment and blindness with no cure currently established. Cell replacement is discussed as a potential therapy for AMD. Besides intravitreal injection and subretinal injection, intravenous administration has been explored as an alternative route. This study is to observe the effect of BSYJ, a traditional Chinese medicine on the homing and differentiation of mesenchymal stem cells transplanted via tail vein injection in an age-related macular degeneration mouse model. Methods: Four-week-old C57BL/6J mice were injected with 40 mg/kg NaIO₃ to induce age-related macular degeneration model. At the second day after NaIO₃ injection, 1×10⁷ GFP labeled bone marrow-derived mesenchymal stem cells (GFP-MSCs) were transplanted via tali vein injection into the experimental mice. Then the mice were randomly divided into two groups, gavaged with either BSYJ solution (BSYJ group, n=12) or distilled water (DW group, n=12). 12 age-matched healthy C57BL/6J mice were fed regularly as normal control. At day 7, day 14, and day 28 after treatment, retina flat mounting was used to detect the homing of mesenchymal stem cells at the retina. Double-labeling immunofluorescence was used to determine the differentiation of mesenchymal stem cells. Results: At 7, 14, 28 days after treatment, the numbers of GFP-MSCs detected by retina flatmount were 10.2 ± 2.5, 14.5 ± 3.4 and 18.7 ± 5.8, respectively in the distilled water group, while 15.7 ± 3.8, 32.3 ± 3.5 and 77.3 ± 6.4 in BSYJ group, the differences between the two groups were significant (p < 0.05). At 28 days after treatment, it was shown by double staining immunofluorescence that there were more GFP positive cells in the retina of BSYJ group than that of the DW group, but none of the cells expressed RPE specific genes such as RPE65 and CRALBP, or photoreceptor genes such as recoverin and rhodopsin either in BSYJ group or DW group. However, GFAP positive cells were found among the cells labeled with GFP, and the double labeling cells were much more in the BSYJ group than the distilled water group. Conclusion: BSYJ could promote homing of mesenchymal stem cells at the retina of age-related macular degeneration model mice induced by NaIO₃, and the differentiation towards to glial cells. Acknowledgement: National Natural Foundation of China (No: 81473736, 81674033,81973912).

Keywords: BSYJ, differentiation, homing, mesenchymal stem cells

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Authors: P. I. Bobyleva, E. R. Andreeva, I. V. Andrianova, E. V. Maslova, L. B. Buravkova

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This work studied the ability of adipose tissue-derived mesenchymal stromal cells (MSCs) to form stroma for expansion of cord blood hematopoietic cells. We showed that 72-hour interaction of MSCs with cord blood mononuclear cells (MNCs) in vitro at atmospheric (20%) and low (5%) O2 conditions increased the expression of ICAM-1, HCAM (at the beginning of interaction) on MSCs. Viability of MSCs and MNCs were maintained at high level. Adhesion of MNCs to MSCs was faster at 20% O2. MSCs promoted the proliferation of adhered MNCs to form the suspension containing great number of hematopoietic colony-forming units, and this effect was more pronounced at 5% O2. Thus, adipose-derived MSCs supplied sufficient stromal support to cord blood MNCs both at 20% and 5% О2, providing their adhesion with further expansion of new generation of different hematopoietic lineages.

Keywords: hematopoietic stem and progenitor cells, mesenchymal stromal cells, tissue-related oxygen, adipose tissue

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Authors: Purwati, Sony Wibisono, Ari Sutjahjo, Askandar T. J., Fedik A. Rantam

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Diabetes mellitus type 2 (T2DM), also known as hyperglycemia, results from insulin resistance and relative insulin deficiency. Diabetes mellitus is the main cause of premature death, particularly among individuals under the age of 70 years old. Mesenchymal stem cells (MSCs) can release bioactive molecules that promote tissue repair and regeneration. Hence, in this research, we evaluated the potential of autologous adipose-derived mesenchymal stem cells (AD-MSCs) in 40 patients of phase I clinical trial in T2DM with various ages between 30-79 years. AD-MSCs are transferred through catheterization. MSCs were validated by measures of CD105+ and CD34- expression. The result showed that after AD-MSCs transplantation, blood glucose levels (fasting and 2-hour postprandial) and insulin levels were significantly decreasing. Besides that, the level of HbA1c significantly decreased after three months of AD-MSCs injection and increasing level of c-peptide after injection. Thus, we conclude that AD-MSCs injection has the potential for T2DM therapy.

Keywords: glucose, hyperglycemia, MSCs, T2DM

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Authors: Ali A. Alshatwi, Vaiyapuri S. Periasamy, Jegan Athinarayanan

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Engineered nanoparticles’ usage rapidly increased in various applications in the last decade due to their unusual properties. However, there is an ever increasing concern to understand their toxicological effect in human health. Particularly, metal and metal oxide nanoparticles have been used in various sectors including biomedical, food and agriculture. But their impact on human health is yet to be fully understood. In this present investigation, we assessed the toxic effect of engineered nanoparticles (ENPs) including Ag, MgO and Co3O4 nanoparticles (NPs) on human mesenchymal stem cells (hMSC) adopting cell viability and cellular morphological changes as tools The results suggested that silver NPs are more toxic than MgO and Co3O4NPs. The ENPs induced cytotoxicity and nuclear morphological changes in hMSC depending on dose. The cell viability decreases with increase in concentration of ENPs. The cellular morphology studies revealed that ENPs damaged the cells. These preliminary findings have implications for the use of these nanoparticles in food industry with systematic regulations.

Keywords: cobalt oxide, human mesenchymal stem cells, MgO, silver

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Laila Montaser, Hala Gabr, Maha El-Bassuony, Gehan Tawfeek

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Orthotropic liver transplantation (OLT) is the final procedure of both end stage and metabolic liver diseases. Hepatocyte transplantation is an alternative for OLT, but the sources of hepatocytes are limited. Bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into hepatocyte-like cells and are a potential alternative source for hepatocytes. The MSCs from bone marrow are a promising target population as they are capable of differentiating along multiple lineages and, at least in vitro, have significant expansion capability. MSCs from bone marrow may have the potential to differentiate in vitro and in vivo into hepatocytes. Our study examined whether mesenchymal stem cells (MSCs), which are stem cells originated from human bone marrow, are able to differentiate into functional hepatocyte-like cells in vitro. Our aim was to investigate the differentiation potential of BM-MSCs into hepatocyte-like cells. Adult stem cell therapy could solve the problem of degenerative disorders, including liver disease.

Keywords: bone marrow, differentiation, hepatocyte, stem cells

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Authors: Saimir Heta, Ilma Robo, Dhimiter Papakozma, Eduart Kapaj, Vera Ostreni

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Introduction: The biocompatible materials applied to the implant surfaces are the target of recent literature studies. Methodologies: Modification of implant surfaces in different ways such as application of additional ions, surface microstructure change, surface or laser ultrasound alteration, or application of various substances such as recombinant proteins are among the most affected by articles published in the literature. The study is of review type with the main aim of finding the different ways that the mesenchymal cell reaction to these materials is, according to the literature, in the same percentage positive to the osteointegration process. Results: It is emphasized in the literature that implant success as a key evaluation key has more to implement implant treatment protocol ranging from dental health amenity and subsequent of the choice of implant type depending on the alveolar shape of the ridge level. Conclusions: Osteointegration is a procedure that should initially be physiologically independent of the type of implant pile material. With this physiological process, it can not "boast" for implant success or implantation depending on the brand of the selected implant, as the breadth of synthetic or natural materials that promote osteointegration is relatively large.

Keywords: mesenchymal cells, implants, review, biocompatible materials

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: Do Khanh Vy, Vuong Cat Khanh, Osamu Ohneda

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During atherosclerosis (AS) progression, perivascular adipose tissue-derived mesenchymal stem cells (PVAT-MSCs) are exposed to the hypoxic environment due to the oxygenic deprivation which might influence the adipose tissue-derived mesenchymal stem cells (AT-MSCs) function. Additionally, it has been reported that the angiogenic ability of subcutaneous AT-MSCs (SAT-MSCs) was impaired in the AS patients. However, up to now, the effects of AS on the characteristics and function of PVAT-MSCs have not been clarified yet. In the present study, we analyzed the AS microenvironment effects on the characteristics and function of AT-MSCs. We found that there was no significant difference in cellular morphology and differentiation ability between SAT-MSCs and PVAT-MSCs in AS patients. However, the proliferation of AS-derived PVAT-MSCs was less than those of AS-derived SAT-MSCs. Importantly, the migration of AS-derived PVAT-MSCs was faster than AS-derived SAT-MSCs. Of note, AS-derived PVAT-MSCs showed the upregulation of SDF1, which is related to the homing, and VEGF, which is related to the angiogenesis compared to those of AS-derived SAT-MSCs. Consistent with these results, AS-derived PVAT-MSCs showed the higher ability to recruit EPCs and ECs than AS-derived SAT-MSCs. In addition, EPCs and ECs which cultured in the presence of AS-derived PVAT-MSC conditioned medium showed the higher angiogenic function of the tube formation compared to those cultured in AS-derived SAT-MSC conditioned medium. This result suggests that the higher paracrine effects of AS-derived PVAT-MSCs support the angiogenic function of the target cells. Our data showed the different characteristics and functions of AT-MSCs derived from different sources of tissues. Under the AS microenvironment, it seems that the characteristics and functions of PVAT-MSCs might reflect the progression of AS. Further study will be necessary to clarify the mechanism in the future.

Keywords: atherosclerosis, mesenchymal stem cells, perivascular adipose tissue, subcutaneous adipose tissue

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Authors: Mohammad Nasb, Muhammad Rehan, Chen Hong

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Background Meniscus defects critically alter knee function and lead to degenerative changes. Regenerative medicine applications including stem cell transplantation have showed a promising efficacy in finding alternatives to overcome traditional treatment limitations. However, stem cell therapy remains limited due to the substantially reduced viability and inhibitory microenvironment. Since tissue growth and repair are under the control of biochemical and mechanical signals, several approaches have recently been investigated (e.g., low intensity pulsed ultrasound [LIPUS]) to promote the regeneration process. This study employed LIPUS to improve growth and osteogenic differentiation of mesenchymal stem cells derived from human embryonic stem cells to improve the regeneration of meniscus tissue. Methodology: The Mesenchymal stromal cells (MSCs) were transplanted into the epicenter of the injured meniscus in rabbits, which were randomized into two main groups: a treatment group (n=32 New Zealand rabbits) including 4 subgroups of 8 rabbits in each subgroup (LIPUS treatment, MSC treatment, LIPUS with MSC and control), and a second group (n=9) to track implanted cells and their progeny using green fluorescence protein (GFP). GFP consists of the MSC and LIPUS-MSC combination subgroups. Rabbits were then subjected to histological, immunohistochemistry, and MRI assessment. Results: The quantity of the newly regenerated tissue in the combination treatment group that had Ultrasound irradiation after mesenchymal stem cells were better at all end points. Likewise, Tissue quality scores were also greater in knees treated with both approaches compared with controls and single treatment at all end points, achieving significance at twelve and twenty-four weeks [p < 0.05], and [p = 0.008] at twelve weeks. Differentiation into type-I and II collagen-expressing cells were higher in the combination group at up to twenty-four weeks. Conclusions: the combination of mesenchymal stem cells and LIPUS showed greater adhering to the sites of meniscus injury, differentiate into cells resembling meniscal fibrochondrocytes, and improve both quality and quantity of meniscal regeneration.

Keywords: stem cells, regenerative medicine, osteoarthritis, knee

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Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc

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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.

Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials

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Authors: S. S. Salehi, A. Shamloo

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Poor ability of cartilage tissue when experiencing a damage leads scientists to use tissue engineering as a reliable and effective method for regenerating or replacing damaged tissues. An artificial tissue should have some features such as biocompatibility, biodegradation and, enough mechanical properties like the original tissue. In this work, a composite hydrogel is prepared by using natural and synthetic materials that has high porosity. Mechanical properties of different combinations of polymers such as modulus of elasticity were tested, and a hydrogel with good mechanical properties was selected. Bone marrow derived mesenchymal stem cells were also seeded into the pores of the sponge, and the results showed the adhesion and proliferation of cells within the hydrogel after one month. In comparison with previous works, this study offers a new and efficient procedure for the fabrication of cartilage like tissue and further cartilage repair.

Keywords: cartilage tissue engineering, hydrogel, mechanical strength, mesenchymal stem cell

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Authors: Ghasem Yazdanpanah, Mona Kakavand, Hassan Niknejad

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Objectives: An important issue in tissue engineering (TE) is hemocompatibility. The current engineered vessels are seriously at risk of thrombus formation and stenosis. Amnion (AM) is the innermost layer of fetal membranes that consists of epithelial and mesenchymal sides. It has the advantages of low immunogenicity, anti-inflammatory and anti-bacterial properties as well as good mechanical properties. We recently introduced the amnion as a natural biomaterial for tissue engineering. In this study, we have evaluated hemocompatibility of amnion as potential biomaterial for tissue engineering. Materials and Methods: Amnions were derived from placentas of elective caesarean deliveries which were in the gestational ages 36 to 38 weeks. Extracted amnions were washed by cold PBS to remove blood remnants. Blood samples were obtained from healthy adult volunteers who had not previously taken anti-coagulants. The blood samples were maintained in sterile tubes containing sodium citrate. Plasma or platelet rich plasma (PRP) were collected by blood sample centrifuging at 600 g for 10 min. Hemocompatibility of the AM samples (n=7) were evaluated by measuring of activated partial thromboplastin time (aPTT), prothrombin time (PT), hemolysis, and platelet aggregation tests. P-selectin was also assessed by ELISA. Both epithelial and mesenchymal sides of amnion were evaluated. Glass slide and expanded polytetrafluoroethylene (ePTFE) samples were defined as control. Results: In comparison with glass as control (13.3 ± 0.7 s), prothrombin time was increased significantly while each side of amnion was in contact with plasma (p<0.05). There was no significant difference in PT between epithelial and mesenchymal surfaces (17.4 ± 0.7 s vs. 15.8 ± 0.7 s, respectively). However, aPPT was not significantly changed after incubation of plasma with amnion epithelial and mesenchymal surfaces or glass (28.61 ± 1.39 s, 31.4 ± 2.66 s, glass, 30.76 ± 2.53 s, respectively, p>0.05). Amnion surfaces, ePTFE and glass samples have less hemolysis induction than water considerably (p<0.001), in which no differences were detected. Platelet aggregation measurements showed that platelets were less stimulated by the amnion epithelial and mesenchymal sides, in comparison with ePTFE and glass. In addition, reduction in amount of p-selectin, as platelet activation factor, after incubation of samples with PRP indicated that amnion has less stimulatory effects on platelets than ePTFE and glass. Conclusion: Amnion as a natural biomaterial has the potential to be used in tissue engineering. Our results suggest that amnion has appropriate hemocompatibility to be employed as a vascular substitute.

Keywords: amnion, hemocompatibility, tissue engineering, biomaterial

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Authors: Gileade P. Freitas, Helena B. Lopes, Alann T. P. Souza, Paula G. F. P. Oliveira, Adriana L. G. Almeida, Paulo G. Coelho, Marcio M. Beloti, Adalberto L. Rosa

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Bone tissue presents great capacity to regenerate when injured by trauma, infectious processes, or neoplasia. However, the extent of injury may exceed the inherent tissue regeneration capability demanding some kind of additional intervention. In this scenario, cell therapy has emerged as a promising alternative to treat challenging bone defects. This study aimed at evaluating the effect of local injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs) on bone regeneration of rat calvaria defects. BM-MSCs and AT-MSCs were isolated and characterized by expression of surface markers; cell viability was evaluated after injection through a 21G needle. Defects of 5 mm in diameter were created in calvaria and after two weeks a single injection of BM-MSCs, AT-MSCs or vehicle-PBS without cells (Control) was carried out. Cells were tracked by bioluminescence and at 4 weeks post-injection bone formation was evaluated by micro-computed tomography (μCT) and histology, nanoindentation, and through gene expression of bone remodeling markers. The data were evaluated by one-way analysis of variance (p≤0.05). BM-MSCs and AT-MSCs presented characteristics of mesenchymal stem cells, kept viability after passing through a 21G needle and remained in the defects until day 14. In general, injection of both BM-MSCs and AT-MSCs resulted in higher bone formation compared to Control. Additionally, this bone tissue displayed elastic modulus and hardness similar to the pristine calvaria bone. The expression of all evaluated genes involved in bone formation was upregulated in bone tissue formed by BM-MSCs compared to AT-MSCs while genes involved in bone resorption were upregulated in AT-MSCs-formed bone. We show that cell therapy based on the local injection of BM-MSCs or AT-MSCs is effective in delivering viable cells that displayed local engraftment and induced a significant improvement in bone healing. Despite differences in the molecular cues observed between BM-MSCs and AT-MSCs, both cells were capable of forming bone tissue at comparable amounts and properties. These findings may drive cell therapy approaches toward the complete bone regeneration of challenging sites.

Keywords: cell therapy, mesenchymal stem cells, bone repair, cell culture

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Authors: Fatma Y. Meligy

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Objectives: The objectives of this study aimed to isolate and characterize mesenchymal stem cells (MSCs) derived from synovial membrane. Then to assess the potentiality of myogenic differentiation of these isolated MSCs. Methods: The MSCs were isolated from synovial membrane by digestion method. Three adult rats were used. The 5 -azacytidine was added to the cultured cells for one day. The isolated cells and treated cells are assessed using immunoflouresence, flowcytometry, PCR and real time PCR. Results: The isolated stem cells showed morphological aspect of stem cells they showed strong positivity to CD44 and CD90 in immunoflouresence while in CD34 and CD45 showed negative reaction. The treated cells with 5-azacytidine was shown to have positive reaction for desmin. Flowcytometric analysis showed that synovial MSCs had strong positive percentage for CD44(%98)and CD90 (%97) and low percentage for CD34 & CD45 while the treated cells showed positive percentage for myogenic marker myogenin (85%). As regard the PCR and Real time PCR, the treated cells showed positive reaction to the desmin primer. Conclusion: The adult MSCs were isolated successfully from synovial membrane and characterized with stem cell markers. The isolated cells could be differentiated in vitro into myogenic cells. These differentiated cells could be used in auto-replacement of diseased or traumatized muscle cells as a regenerative therapy for muscle disorders and trauma.

Keywords: mesenchymal stem cells, synovial membrane, myogenic differentiation

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Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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Authors: K. Mardaleishvili, G. Loladze, G. Shatirishivili, D. Chakhunashvili, A. Vishnevskaya, Z. Kakabadze

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Benign osteoblastoma is a benign tumor of the bone, usually affecting the vertebrae and long tubular bones. It is a rarely seen tumor of the facial bones. The authors present a case of a 28-year-old male patient with a tumor in mandibular body. The lesion was radically resected and histological analysis of the specimen demonstrated features typical of a benign osteoblastoma. The defect of the jaw was reconstructed with titanium implants and decellularized and lyophilized cattle bone matrix with mesenchymal bone marrow stem cells transplantation. This presentation describes the procedures for rehabilitating a patient with decellularized bone scaffold in the region of the face, recovering the facial contours and esthetics of the patient.

Keywords: facial bones, osteoblastoma, stem cells, transplantation

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Authors: Halima Albalushi, Mohadese Boroojerdi, Murtadha Alkhabori

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Introduction: Maintenance of stem cell properties during culture necessitates the recreation of the natural cell niche. Studies reported the promising outcome of mesenchymal stem cells (MSC) properties maintenance after using extracellular matrix such as CELLstart™, which is the recommended coating material for stem cells cultured in serum-free and xeno-free conditions. Laminin-521 is known as a crucial adhesion protein, which is found in natural stem cell niche, and plays an important role in facilitating the maintenance of self-renewal, pluripotency, standard morphology, and karyotype of human pluripotent stem cells (PSCs). The aim of this study is to investigate the effects of Laminin-521 on human umbilical cord-derived mesenchymal stem cells (UC-MSC) characteristics as a step toward clinical application. Methods: Human MSC were isolated from the umbilical cord via the explant method. Umbilical cord-derived-MSC were cultured in serum-free and xeno-free conditions in the presence of Laminin-521 for six passages. Cultured cells were evaluated by morphology and expansion index for each passage. Phenotypic characterization of UC-MSCs cultured on Laminin-521 was evaluated by assessment of cell surface markers. Results: Umbilical cord derived-MSCs formed small colonies and expanded as a homogeneous monolayer when cultured on Laminin-521. Umbilical cord derived-MSCs reached confluence after 4 days in culture. No statistically significant difference was detected in all passages when comparing the expansion index of UC-MSCs cultured on LN-521 and CELLstart™. Phenotypic characterization of UC-MSCs cultured on LN-521 using flow cytometry revealed positive expression of CD73, CD90, CD105 and negative expression of CD34, CD45, CD19, CD14 and HLA-DR.Conclusion: Laminin-521 is comparable to CELLstart™ in supporting UC-MSCs expansion and maintaining their characteristics during culture in xeno-free and serum-free culture conditions.

Keywords: mesenchymal stem cells, culture, laminin-521, xeno-free serum-free

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Authors: Jung Park, Anca Mazare, Klaus Von Der Mark, Patrik Schmuki

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In clinical application of TiO2 implants on tooth and hip replacement, migration, adhesion and differentiation of neighboring mesenchymal stem cells onto implant surfaces are critical steps for successful bone regeneration. In a recent decade, accumulated attention has been paid on nanoscale electrochemical surface modifications on TiO2 layer for improving bone-TiO2 surface integration. We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and here we show that mesenchymal stem cells finely sense TiO2 nanotubular geometry and quickly decide their cell fate either to differentiation into osteoblasts or to programmed cell death (apoptosis) on TiO2 nanotube layers. These cell fate decisions are critically dependent on nanotube size differences (15-100nm in diameters) of TiO2 nanotubes sensing by integrin clustering. We further demonstrate that nanoscale topography-sensing is feasible not only in mesenchymal stem cells but rather seems as generalized nanoscale microenvironment-cell interaction mechanism in several cell types composing bone tissue network including osteoblasts, osteoclast, endothelial cells and hematopoietic stem cells. Additionally we discuss the synergistic effect of simultaneous stimulation by nanotube-bound growth factor and nanoscale topographic cues on enhanced bone regeneration.

Keywords: TiO2 nanotube, stem cell fate decision, nano-scale microenvironment, bone regeneration

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Authors: Eva Filová, Jana Daňková, Věra Sovková, Matej Daniel

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Titanium alloys are biocompatible metals that are widely used in clinical practice as load bearing implants. The chemical modification may influence cell adhesion, proliferation, and differentiation as well as stiffness of the material. The aim of the study was to evaluate the adhesion, growth and differentiation of pig mesenchymal stem cells on the novel beta titanium alloy Ti36Nb6Ta compared to standard medical titanium alloy Ti6Al4V. Discs of Ti36Nb6Ta and Ti6Al4V alloy were sterilized by ethanol, put in 48-well plates, and seeded by pig mesenchymal stem cells at the density of 60×103/cm2 and cultured in Minimum essential medium (Sigma) supplemented with 10% fetal bovine serum and penicillin/streptomycin. Cell viability was evaluated using MTS assay (CellTiter 96® AQueous One Solution Cell Proliferation Assay;Promega), cell proliferation using Quant-iT™ ds DNA Assay Kit (Life Technologies). Cells were stained immunohistochemically using monoclonal antibody beta-actin, and secondary antibody conjugated with AlexaFluor®488 and subsequently the spread area of cells was measured. Cell differentiation was evaluated by alkaline phosphatase assay using p-nitrophenyl phosphate (pNPP) as a substrate; the reaction was stopped by NaOH, and the absorbance was measured at 405 nm. Osteocalcin, specific bone marker was stained immunohistochemically and subsequently visualized using confocal microscopy; the fluorescence intensity was analyzed and quantified. Moreover, gene expression of osteogenic markers osteocalcin and type I collagen was evaluated by real-time reverse transcription-PCR (qRT-PCR). For statistical evaluation, One-way ANOVA followed by Student-Newman-Keuls Method was used. For qRT-PCR, the nonparametric Kruskal-Wallis Test and Dunn's Multiple Comparison Test were used. The absorbance in MTS assay was significantly higher on titanium alloy Ti6Al4V compared to beta titanium alloy Ti36Nb6Ta on days 7 and 14. Mesenchymal stem cells were well spread on both alloys, but no difference in spread area was found. No differences in alkaline phosphatase assay, fluorescence intensity of osteocalcin as well as the expression of type I collagen, and osteocalcin genes were observed. Higher expression of type I collagen compared to osteocalcin was observed for cells on both alloys. Both beta titanium alloy Ti36Nb6Ta and titanium alloy Ti6Al4V Ti36Nb6Ta supported mesenchymal stem cellsˈ adhesion, proliferation and osteogenic differentiation. Novel beta titanium alloys Ti36Nb6Ta is a promising material for bone implantation. The project was supported by the Czech Science Foundation: grant No. 16-14758S, the Grant Agency of the Charles University, grant No. 1246314 and by the Ministry of Education, Youth and Sports NPU I: LO1309.

Keywords: beta titanium, cell growth, mesenchymal stem cells, titanium alloy, implant

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Abbas Jafarizad, Duygu Ekinci

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In this work targeted drug delivery is proposed to decrease adverse effect of drugs with concomitant reduces in consumption and treatment outgoings. Nanoparticles (NPs) can be prepared from a variety of materials such as lipid, biodegradable polymer that prevent the drugs cytotoxicity in healthy cells, etc. One of the most important drugs used in chemotherapy is mitoxantrone (MTX) which prevents cell proliferation by inhibition of topoisomerase II and DNA repair; however, it is not selective and has some serious side effects. In this study, mentioned aim is achieved by using several nanocarriers like magnetite (Fe3O4) and their composites with magnetic graphene oxide (Fe3O4@GO). Also, cytotoxic potential of Fe3O4, Fe3O4-MTX, and Fe3O4@GO-MTX nanocomposite were evaluated on mesenchymal stem cells (MSCs). In this study, we reported the synthesis of monodisperse Fe3O4 NPs and Fe3O4@GO nanocomposite and their structures were investigated by using field emission scanning electron microscope (FESEM), Fourier transform infrared (FTIR) spectra, atomic force microscopy (AFM), Brauneur Emmet Teller (BET) isotherm and contact angle studies. Moreover, we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate cytotoxic effects of MTX, Fe3O4 NPs, Fe3O4-MTX and Fe3O4@GO-MTX nanocomposite on MSCs. The in-vitro MTT results indicated that all concentrations of MTX and Fe3O4@GO-MTX nanocomposites showed cytotoxic effects while all concentrations of Fe3O4 NPs and Fe3O4-MTX NPs did not show any cytotoxic effect on stem cells. The results from this study indicated that using Fe3O4 NPs as anticancer drug delivery systems could be a trustworthy method for cancer treatment. But for reaching excellent and accurate results, further investigation is necessary.

Keywords: mitoxantrone, magnetite, magnetic graphene oxide, MTT assay, mesenchymal stem cells

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Authors: Mahmoud M. Zakaria, Omnia F. Elmoursi, Mahmoud M. Gabr, Camelia A. AbdelMalak, Mohamed A. Ghoneim

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Many protocols were publicized for differentiation of human mesenchymal stem cells (MSCS) into insulin-producing cells (IPCs) in order to excrete insulin hormone ingoing to treat diabetes disease. Our aim is to evaluate relative gene expression for each independent protocol. Human bone marrow cells were derived from three volunteers that suffer diabetes disease. After expansion of mesenchymal stem cells, differentiation of these cells was done by three different protocols (the one-step protocol was used conophylline protein, the two steps protocol was depending on trichostatin-A, and the three-step protocol was started by beta-mercaptoethanol). Evaluation of gene expression was carried out by real-time PCR: Pancreatic endocrine genes, transcription factors, glucose transporter, precursor markers, pancreatic enzymes, proteolytic cleavage, extracellular matrix and cell surface protein. Quantitation of insulin secretion was detected by immunofluorescence technique in 24-well plate. Most of the genes studied were up-regulated in the in vitro differentiated cells, and also insulin production was observed in the three independent protocols. There were some slight increases in expression of endocrine mRNA of two-step protocol and its insulin production. So, the two-step protocol was showed a more efficient in expressing of pancreatic endocrine genes and its insulin production than the other two protocols.

Keywords: mesenchymal stem cells, insulin producing cells, conophylline protein, trichostatin-A, beta-mercaptoethanol, gene expression, immunofluorescence technique

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Authors: Jana Stepanovska, Roman Matejka, Jozef Rosina, Marta Vandrovcova, Lucie Bacakova

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The aim of this study was to develop a system for mechanical and also electrical stimulation controlling in vitro osteogenesis under conditions more similar to the in vivo bone microenvironment than traditional static cultivation, which would achieve good adhesion, growth and other specific behaviors of osteogenic cells in cultures. An engineered culture system for mechanical stimulation of the mesenchymal stem cells on the charged surface was designed. The bioreactor allows efficient mechanical loading inducing an electrical response and perfusion of the culture chamber with seeded cells. The mesenchymal stem cells were seeded to specific charged materials, like polarized hydroxyapatite (Hap) or other materials with piezoelectric and ferroelectric features, to create electrical potentials for stimulating of the cells. The material of the matrix was TiNb alloy designed for these purposes, and it was covered by BaTiO3 film, like a kind of piezoelectric material. The process of mechanical stimulation inducing electrical response is controlled by measuring electrical potential in the chamber. It was performed a series of experiments, where the cells were seeded, perfused and stimulated up to 48 hours under different conditions, especially pressure and perfusion. The analysis of the proteins expression was done, which demonstrated the effective mechanical and electrical stimulation. The experiments demonstrated effective stimulation of the cells in comparison with the static culture. This work was supported by the Ministry of Health, grant No. 15-29153A and the Grant Agency of the Czech Republic grant No. GA15-01558S.

Keywords: charged surface, dynamic cultivation, electrical stimulation, ferroelectric layers, mechanical stimulation, piezoelectric layers

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Authors: Katarzyna Drela, Miroslaw Wielgos, Mikolaj Wrobel, Barbara Lukomska

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Mesenchymal stem cells (MSCs) have a great potential in regenerative medicine. Since the initial number of isolated MSCs is limited, in vitro propagation is often required to reach sufficient numbers of cells for therapeutic applications. During long-term culture MSCs may undergo genetic or epigenetic alterations that subsequently increase the probability of spontaneous malignant transformation. Thus, factors that influence genomic stability of MSCs following long-term expansions need to be clarified before cultured MSCs are employed for clinical application. The aim of our study was to investigate the potential for spontaneous transformation of human neonatal cord blood (HUCB-MSCs) and adult bone marrow (BM-MSCs) derived MSCs. Materials and Methods: HUCB-MSCs and BM-MSCs were isolated by standard Ficoll gradient centrifugations method. Isolated cells were initially plated in high density 106 cells per cm2. After 48 h medium were changed and non-adherent cells were removed. The malignant transformation of MSCs in vitro was evaluated by morphological changes, proliferation rate, ability to enter cell senescence, the telomerase expression and chromosomal abnormality. Proliferation of MSCs was analyzed with WST-1 reduction method and population doubling time (PDT) was calculated at different culture stages. Then the expression pattern of genes characteristic for mesenchymal or epithelial cells, as well as transcriptions factors were examined by RT-PCR. Concomitantly, immunocytochemical analysis of gene-related proteins was employed. Results: Our studies showed that MSCs from all bone marrow isolations ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUCB-MSCs from one of the 15 donors displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. In this sample we observed two different cell phenotypes: one mesenchymal-like exhibited spindle shaped morphology and express specific mesenchymal surface markers (CD73, CD90, CD105, CD166) with low proliferation rate, and the second one with round, densely package epithelial-like cells with significantly increased proliferation rate. The PDT of epithelial-like populations was around 1day and 100% of cells were positive for proliferation marker Ki-67. Moreover, HUCB-MSCs showed a positive expression of human telomerase reverse transcriptase (hTERT), cMYC and exhibit increased number of CFU during the long-term culture in vitro. Furthermore, karyotype analysis revealed chromosomal abnormalities including duplications. Conclusions: Our studies demonstrate that HUCB-MSCs are susceptible to spontaneous malignant transformation during long-term culture. Spontaneous malignant transformation process following in vitro culture has enormous effect on the biosafety issues of future cell-based therapies and regenerative medicine regimens.

Keywords: mesenchymal stem cells, spontaneous, transformation, long-term culture

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Authors: Emanuela Chiarella, Clelia Nisticò, Nicola Lombardo, Giovanna Lucia Piazzetta, Nadia Lobello, Maria Mesuraca

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Killian’s Antrochoanal Polyp is a benign lesion of the maxillary sinus characterized by unilateral nasal obstruction, pus discharge, and headache. It affects, more commonly children and young adults. Although its etiology still remains unclear, chronic inflammation, autoreactivity, allergies, and viral infections are strongly associated with its formation and development, resulting in nasal tissue remodeling. We aimed to investigate the stem cells components which reside in this pathological tissue. In particular, we adopted a protocol for the isolation and culturing of mesenchymal stem cells from surgical biopsies of three Killian nasal polyp patients (KNP-MSCs) as well as from their healthy nasal tissue (HNT-MSCs) that were used as controls. The immunophenotype profile of HNT-MSCs and KNP-MSCs was more similar, with a marked positivity for CD73, CD90, and CD105 expression, while being negative for CD34 and CD14 haematopoietic genes. Cell proliferation assay showed that KNP-MSCs had a replicative disadvantage compared to HNT-MSCs, as evidenced by the significantly lower number of cells in the S-phase of the cell cycle. KNP-MSCs also took longer to close a wound than HNT-MSCs, indicating a partial epithelial phenotype in which low levels of ICAM-1 mRNA and a significant increase in E-CAD transcript were detectable. Subsequently, the differentiation potential of both MSCs populations was analyzed by inducing osteoblastic or adipocyte differentiation for up to 20 days. KNP-MSCs showed the ability to differentiate into osteoblasts, although ALP activity as well as the number and size of calcium deposits were lower than osteogenic induced-HNT-MSCs. Also, mRNA levels of osteoblastic marker genes (OCN, OPN, OSX, RUNX2) resulted lower compared to control cell population. Instead, the analysis of the adipogenic differentiation potential showed a similar behavior between KNP-MSCs and HNT-MSCs considering that the amount of lipid droplets, the expression of adipocyte-specific genes (FABP4, AdipoQ, PPARγ2, LPL) and the content of triacylglycerols were almost overlapping. Taken together, these results first demonstrated that Killian's nasal polyp is a source of mesenchymal stem cells with self-renewal and multi-differentiative capabilities.

Keywords: Mesenchymal stem cells, adipogenic differentiation, osteogenic differentiation, EMT

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Authors: Pardis Abolghasemi, Benyamin Hatamsaz

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Background: Diabetic nephropathy is a serious health problem described by specific kidney structure and functional disturbance. Renoprotective effects of the stem cells secretase have been shown in many kidney diseases. The aim is to evaluate the capability of human Wharton’s jelly mesenchymal stem cells conditioned media (hWJMSCs-CM) to alleviate DN in streptozotocin (STZ)-induced diabetes. Methods: Diabetic nephropathy was induced by injection of STZ (60 mg/kg, IP) in twenty rats. Conditioned media was extracted from hWJMSCs at third passages. At week 8, diabetic rats were divided into two groups: treated (hWJMSCs-CM, 500 μl/rat for three weeks, IP) and not treated (DN). In the 11th week, three groups (control, DN and DN+hWJMSCs-CM) were kept in metabolic cages and urine was collected for 24h. Blood pressure (BP) and heart rate (HR) were continuously recorded. The serum samples were maintained for measuring BUN, Cr and angiotensin-converting enzyme (ACE) activity. The left kidney was kept at -80°C for ACE activity assessment. The right kidney and pancreas were used for histopathologic evaluation. Result: Diabetic nephropathy was detected by microalbuminuria and increased albumin/creatinine ratio, as well as the pancreas and renal structural disturbance. Glomerular filtration rate, BP and HR increased in the DN group. The ACE activity was elevated in the serum and kidneys of the DN group. Administration of hWJMSCs-CM modulated the renal functional and structural disturbance and decreased the ACE activity. Conclusion: Conditioned media was extracted from hWJMSCs may have a Renoprotective effect in diabetic nephropathy. This may happen through regulation of ACE activity and renin-angiotensin system inhibition.

Keywords: diabetic nephropathy, mesenchymal stem cells, immunomodulation, anti-inflammation

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Authors: Parcha Sreenivasa Rao, P. Lakshmi

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Diabetes Mellitus is metabolic disorder, characterized by high glucose levels in the blood due to one of the reason i.e., the death of β cells. The lack of β cells leads to the reduced insulin levels. The β cell death generally occurs due to apoptosis induced by the several cytokines. IL-1β, IFN- ϒ and TNF –α cytokines that are generally cause apoptosis to the β cell. The nutrient based apoptosis is generally seen with high glucose and free fatty acids. It is also noted that the β cell death triggered by Fas ligand and its receptor Fas at the surface of the activated CD8+ T- lymphocytes. Reports also reveal that the β cell apoptosis is under control of the transcription factors NF-kB and STAT- 1. The arresting or opposing of the β cell apoptosis can be overcome by the different growth factors like GLP-1, growth hormone, prolactin, VEGF, Dipeptidyl peptidase-4, Vildagliptin, suberoylanilidehydroxamic acid, trichistatin-A, XIAP, Bcl-2, FGF-21. Present investigation explains antiapoptotic property of the β cells derived from the mesenchymal stem cells of umbilical cord.

Keywords: stem cells, umblical cord, diabetes, apoptosis

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