Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study
- 666 Downloads
Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PDMSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU (P<0.01), and the C-peptide level was increased from 4.1 ±3.7 ng/mL to 5.6 ±3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.
Keywordsplacenta stem cells treatment of type 2 diabetes
Unable to display preview. Download preview PDF.
- 4.Li G, Zhang P, Wang J, Gregg EW, Yang W, Gong Q, Li H, Li H, Jiang Y, An Y, Shuai Y, Zhang B, Zhang J, Thompson TJ, Gerzoff RB, Roglic G, Hu Y, Bennett PH. The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. Lancet, 2008; 24:371 (9626):1783–1789CrossRefGoogle Scholar
- 5.Ciceri F, Piemonti L. Bone marrow and pancreatic islet: an old story with new perspectives. Cell Transplant, 2010 Aug 17Google Scholar
- 11.Lu L L, Liu Y J, Yang S G, Zhao Q J, Wang X, Gong W, Han Z B, Xu Z S, Lu Y X, Liu D, Chen Z Z, Han Z C. Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica, 2006, 91(8): 1017–1026PubMedGoogle Scholar
- 20.Hare J M, Traverse J H, Henry T D, Dib N, Strumpf R K, Schulman S P, Gerstenblith G, DeMaria A N, Denktas A E, Gammon R S, Hermiller J B Jr, Reisman M A, Schaer G L, Sherman W. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol, 2009, 54(24): 2277–2286PubMedCrossRefGoogle Scholar
- 21.Horwitz E M, Prockop D J, Fitzpatrick L A, Koo WW, Gordon P L, Neel M, Sussman M, Orchard P, Marx J C, Pyeritz R E, Brenner M K. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med, 1999, 5(3): 309–313PubMedCrossRefGoogle Scholar
- 22.Kebriaei P, Isola L, Bahceci E, Holland K, Rowley S, McGuirk J, Devetten M, Jansen J, Herzig R, Schuster M, Monroy R, Uberti J. Adult human mesenchymal stem cells added to corticosteroid therapy for the treatment of acute graft-versus-host disease. Biol Blood Marrow Transplant, 2009, 15(7): 804–811PubMedCrossRefGoogle Scholar
- 23.Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler R M, Bacigalupo A, Fibbe W, Ringdén O. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet, 2008, 371(9624): 1579–1586PubMedCrossRefGoogle Scholar
- 26.Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N, Sharma R R, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S, Ramakrishnan S. Efficacy of autologous bone marrow-derived stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cells Dev, 2009, 18(10): 1407–1416PubMedCrossRefGoogle Scholar
- 30.Wang H S, Shyu J F, Shen WS, Hsu H C, Chi T C, Chen C P, Huang S W, Shyr Y M, Tang K T, Chen T H. Transplantation of insulin producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice. Cell Transplant, 2010 Aug 18Google Scholar
- 31.Zhang Y, Dou Z. Transdifferentiation of bone marrow mesenchymal stem cell into islet cells to treat diabetes mellitus. J Cell Biol, 2007, 29: 1–5Google Scholar
- 36.Parolini O, Alviano F, Bagnara G P, Bilic G, Bühring H J, Evangelista M, Hennerbichler S, Liu B, Magatti M, Mao N, Miki T, Marongiu F, Nakajima H, Nikaido T, Portmann-Lanz C B, Sankar V, Soncini M, Stadler G, Surbek D, Takahashi T A, Redl H, Sakuragawa N, Wolbank S, Zeisberger S, Zisch A, Strom S C. Concise review: isolation and characterization of cells from human term placenta: outcome of the first international Workshop on Placenta Derived Stem Cells. Stem Cells, 2008, 26(2): 300–311PubMedCrossRefGoogle Scholar