Safety Study of Intravenously Administered Human Cord Blood Stem Cells in the Treatment of Symptoms Related to Chronic Inflammation

Authors: Brian M. Mehling, Louis Quartararo, Marine Manvelyan, Paul Wang, Dong-Cheng Wu

Abstract:

Numerous investigations suggest that Mesenchymal Stem Cells (MSCs) in general represent a valuable tool for therapy of symptoms related to chronic inflammatory diseases. Blue Horizon Stem Cell Therapy Program is a leading provider of adult and children’s stem cell therapies. Uniquely we have safely and efficiently treated more than 600 patients with documenting each procedure. The purpose of our study is primarily to monitor the immune response in order to validate the safety of intravenous infusion of human umbilical cord blood derived MSCs (UC-MSCs), and secondly, to evaluate effects on biomarkers associated with chronic inflammation. Nine patients were treated for conditions associated with chronic inflammation and for the purpose of antiaging. They have been given one intravenous infusion of UCMSCs. Our study of blood test markers of 9 patients with chronic inflammation before and within three months after MSCs treatment demonstrates that there is no significant changes and MSCs treatment was safe for the patients. Analysis of different indicators of chronic inflammation and aging included in initial, 24-hours, two weeks and three months protocols showed that stem cell treatment was safe for the patients; there were no adverse reactions. Moreover data from follow up protocols demonstrates significant improvement in energy level, hair, nails growth and skin conditions. Intravenously administered UC-MSCs were safe and effective in the improvement of symptoms related to chronic inflammation. Further close monitoring and inclusion of more patients are necessary to fully characterize the advantages of UC-MSCs application in treatment of symptoms related to chronic inflammation.

Keywords: Chronic inflammatory diseases, intravenous infusion, mesenchymal stem cells (MSCs), umbilical cord blood.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1108759

References:

[1] N. Khansari, Y. Shakiba, M. Mahmoudi. Chronic inflammation and oxidative stress as a major cause of age-related diseases and cancer. Recent Pat Inflamm Allergy Drug Discov 2009;3(1):73-80.
[2] P. C. Calder, R. Albers, J. M. Antoine, S. Blum et al. Inflammatory disease processes and interactions with nutrition. Br J Nutr 2009;101 Suppl 1:S1-45.
[3] J. R. Lukens, J. M. Gross, T. D. Kanneganti. IL-1 family cytokines trigger sterile inflammatory disease. Front Immunol 2012; 3: 315
[4] J. Voswinkel, S. Francois, J. M. Simon, M. Benderitter, N. C. Gorin, M. Mohty, L. Fouillard, A. Chapel. Use of mesenchymal stem cells (MSC) in chronic inflammatory fistulizing and fibrotic diseases: a comprehensive review. Clin Rev Allergy Immunol 2013;45(2):180-92.
[5] C. Perdikogianni, H. Dimitriou, E. Stiakaki, G. Martimianaki, M. Kalmanti. Could cord blood be a source of mesenchymal stromal cells for clinical use? Cytotherapy 2008; 10(5):452-9.
[6] A. Erices, P. Conget, J. J. Minguell. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000;109(1):235–242.
[7] P. S. In 't Anker, S. A. Scherjon, C. Kleijburg-van der Keur, G. M. de Groot-Swings, F. H. Claas, W. E. Fibbe et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 2004; 22(7):1338–1345.3.
[8] R. A. Panepucci, J. L. Siufi, W. A. Silva Jr, R. Proto-Siquiera, Neder L, Orellana M, et al. Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 2004; 22(7):1263–1278.
[9] Y. Jiang, B. N. Jahagirdar, R. L. Reinhardt et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418(6893):41-9.
[10] K. Mareschi, I. Ferrero, D. Rustichelli, S. Aschero, L. Gammaitoni, M. Aglietta, E. Madon, F. Fagioli. Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow. J Cell Biochem 2006; 97(4):744-54.
[11] C. Campagnoli, I. A. Roberts, S. Kumar, P. R. Bennett, I. Bellantuono, N. M. Fisk. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bonemarrow. Blood 2001;98(8):2396–2402.
[12] H. S. Wang, S. C. Hung, S. T. Peng, C. C. Huang, H. M. Wei, Y. J. Guo et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004;22(7):1330–1337.
[13] L. F. Wu, N. N. Wang, Y. S. Liu, X. Wei. Differentiation of Wharton's jelly primitive stromal cells into insulin-producing cells in comparison with bone marrow mesenchymal stem cells. Tissue Eng Part A 2009; 15(10):2865-73.
[14] R. Sarugaser, D. Lickorish, D. Baksh, M. M. Hosseini, Davies JE. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 2005;23(2):220–229.
[15] L. L. Lu, Y. J. Liu, S. G. Yang, Q. J. Zhao, X. Wang, W. Gong, et al. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis- supportive function and other potentials. Haematologica 2006;91(8):1017–1026.
[16] A. Can, S. Karahuseyinoglu. Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 2007;25(11):2886–2895.
[17] K. H. Wu, B. Zhou, S. H. Lu, B. Feng, S. G. Yang, W. T. Du et al. In vitro and in vivo differentiation of human umbilical cord derived stem cells into endothelial cells. J Cell Biochem 2007;100(3):608–616.
[18] P. C. Jiang, W. P. Xiong, G. Wang, C. Ma, W. Q. Yao, S. F. Kendell, B. M. Mehling, X. H. Yuan, D. C. Wu. A clinical trial report of autologous bone marrow-derived mesenchymal stem cell transplantation in patients with spinal cord injury. Exp Ther Med 2013;6(1):140-146.
[19] O. Ringdén, M. Uzunel, B. Sundberg, L. Lönnies, S. Nava, J. Gustafsson, L. Henningsohn, K. Le Blanc. Tissue repair using allogeneic mesenchymal stem cells for hemorrhagic cystitis, pneumomediastinum and perforated colon. Leukemia 2007;21(11):2271-6.
[20] D. García-Olmo, M. García-Arranz, D. Herreros, I. Pascual, Peiro C, Rodríguez-Montes JA. A phase I clinical trial of the treatment of Crohn's fistula by adipose mesenchymal stem cell transplantation. Dis Colon Rectum 2005;48(7):1416-23.
[21] K. S. Kang, S. W. Kim, Y. H. Oh, J. W. Yu, K. Y. Kim, H. K. Park, C. H. Song, H. Han. A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study. Cytotherapy 2005;7(4):368-73.
[22] L. Mazzini, K. Mareschi, I. Ferrero, E. Vassallo, G. Oliveri, R. Boccaletti, L. Testa, S. Livigni, F. Fagioli. Autologous mesenchymal stem cells: clinical applications in amyotrophic lateral sclerosis. Neurol Res 2006;28(5):523-6.
[23] A. V. Bystrov, Y. A. Polyaev, M. A. Pogodina, M. F. Rasulov, M. E. Krasheninnikov, N. A. Onishchenko. Use of autologous bone marrow mesenchymal stem cells for healing of free full-thickness skin graft in a zone with pronounced hypoperfusion of soft tissues caused by arteriovenous shunting. Bull Exp Biol Med 2006;142(1):123-8.
[24] V. Falanga, S. Iwamoto, M. Chartier, T. Yufit, J. Butmarc, N. Kouttab, D. Shrayer, P. Carson. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds. Tissue Eng 2007;13(6):1299-312.
[25] G. E. Kilroy, S. J. Foster, X. Wu, J. Ruiz, S. Sherwood, A. Heifetz, J. W. Ludlow, D. M. Stricker, S. Potiny, P. Green, Y. D. Halvorsen, B. Cheatham, R. W. Storms, J. M. Gimble. Cytokine profile of human adipose-derived stem cells: expression of angiogenic, hematopoietic, and pro-inflammatory factors. J Cell Physiol 2007; 212(3):702-9.
[26] E. Meliga, B. M. Strem, H. J. Duckers, P. W. Serruys. Adipose-derived cells. Cell Transplant 2007; 16(9):963-70.
[27] W. S. Kim, B. S. Park, S. H. Park, H. K. Kim, J. H. Sung. Antiwrinkle effect of adipose-derived stem cell: activation of dermal fibroblast by secretory factors. J Dermatol Sci 2009; 53(2):96-102.
[28] H. Nakagawa, S. Akita, M. Fukui, T. Fujii, K. Akino. Human mesenchymal stem cells successfully improve skin-substitute wound healing. Br J Dermatol 2005;153(1):29-36.
[29] S. Zhang, Z. Dong, Z. Peng, F. Lu. Anti-aging effect of adipose-derived stem cells in a mouse model of skin aging induced by D-galactose. PLoS One 2014;9(5):e97573.
[30] K. Al-Refu. Stem cells and alopecia: a review of pathogenesis. Br J Dermatol 2012;167(3):479-84. emonstrated
[31] H. Fukuoka, H. Suga, K. Narita, R. Watanabe, S. Shintani. The Latest Advance in Hair Regeneration Therapy Using Proteins Secreted by Adipose-Derived Stem Cells. The American Journal of Cosmetic Surgery 2012; 29:4.