Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

Ranhua JIANG, Zhibo HAN, Guangsheng ZHUO, Xiaodan QU, Xue LI, Xin WANG, Yuankang SHAO, Shimin YANG, Zhong Chao HAN

PDF(252 KB)
PDF(252 KB)
Front. Med. ›› 2011, Vol. 5 ›› Issue (1) : 94-100. DOI: 10.1007/s11684-011-0116-z
RESEARCH ARTICLE
RESEARCH ARTICLE

Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study

Author information +
History +

Abstract

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 PD-MSC 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.

Keywords

placenta stem cells / treatment of type 2 diabetes

Cite this article

Download citation ▾
Ranhua JIANG, Zhibo HAN, Guangsheng ZHUO, Xiaodan QU, Xue LI, Xin WANG, Yuankang SHAO, Shimin YANG, Zhong Chao HAN. Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study. Front Med, 2011, 5(1): 94‒100 https://doi.org/10.1007/s11684-011-0116-z

References

[1]
Yang W, Lu J, Weng J P, Jia W, Ji L, Xiao J, Shan Z, Liu J, Tian H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zhao Z, Li Q, Zhou Z, Shan G, He J. Prevalence of diabetes among men and women in China. N Engl J Med, 2010, 362(12): 1090–1101
CrossRef Pubmed Google scholar
[2]
Hu D, Sun L, Fu P, Xie J, Lu J, Zhou J, Yu D, Whelton P K, He J, Gu D. Prevalence and risk factors for type 2 diabetes mellitus in the Chinese adult population: the InterASIA Study. Diabetes Res Clin Pract, 2009, 84(3): 288–295
CrossRef Pubmed Google scholar
[3]
Kobayashi N, Yuasa T, Okitsu T. Regenerative medicine for diabetes mellitus. Cell Transplant, 2009, 18(5): 491–496
Pubmed
[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):1783–1789
[5]
Ciceri F, Piemonti L.Bone marrow and pancreatic islet: an old story with new perspectives. Cell Transplant, 2010<month>Aug</month><day>17</day>
[6]
Kodama S, Kühtreiber W, Fujimura S, Dale E A, Faustman D L. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science, 2003, 302(5648): 1223–1227
CrossRef Pubmed Google scholar
[7]
Pittenger M F, Mackay A M, Beck S C, Jaiswal R K, Douglas R, Mosca J D, Moorman M A, Simonetti D W, Craig S, Marshak D R. Multilineage potential of adult human mesenchymal stem cells. Science, 1999, 284(5411): 143–147
CrossRef Pubmed Google scholar
[8]
Deans R J, Moseley A B. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol, 2000, 28(8): 875–884
CrossRef Pubmed Google scholar
[9]
Gronthos S, Franklin D M, Leddy H A, Robey P G, Storms R W, Gimble J M. Surface protein characterization of human adipose tissue-derived stromal cells. J Cell Physiol, 2001, 189(1): 54–63
CrossRef Pubmed Google scholar
[10]
Erices A, Conget P, Minguell J J. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol, 2000, 109(1): 235–242
CrossRef Pubmed Google 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): 1017–1026
Pubmed
[12]
In ’t Anker P S, Scherjon S A, Kleijburg-van der Keur C, de Groot-Swings G M, Claas F H, Fibbe W E, Kanhai H H. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells, 2004, 22(7): 1338–1345
CrossRef Pubmed Google scholar
[13]
Zheng C L, Yang S G, Guo Z X, Liao W, Zhang L, Yang R, Han Z C. Human multipotent mesenchymal stromal cells from fetal lung expressing pluripotent markers and differentiating into cell types of three germ layers. Cell Transplant, 2009, 18(10): 1093–1109
CrossRef Pubmed Google scholar
[14]
Chen K, Wang D, Du W T, Han Z B, Ren H, Chi Y, Yang S G, Zhu D, Bayard F, Han ZC. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol, 2010, 135(3): 448–458
CrossRef Pubmed Google scholar
[15]
Wang D, Chen K, Du W T, Han Z B, Ren H, Chi Y, Yang S G, Bayard F, Zhu D, Han Z C. CD14+ monocytes promote the immunosuppressive effect of human umbilical cord matrix stem cells. Exp Cell Res, 2010, 316(15): 2414–2423
CrossRef Pubmed Google scholar
[16]
Liao W B, Xie J, Zhong J, Liu Y J, Du L, Zhou B, Xu J, Liu P X, Yang S G, Wang J M, Han Z B, Han Z C. Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation, 2009, 87(3): 350–359
CrossRef Pubmed Google scholar
[17]
Zhao Q J, Ren H Y, Li X Y, Chen Z, Zhang X Y, Gong W, Liu Y J, Pang T X, Han Z C. Differentiation of Human umbilical cord mesenchymal stem cells into low immunogenic hepatocyte-like cells. Cytotherapy, 2009, 11(4): 414–426
[18]
Wu K H, Mo X M, Zhou B, Lu S H, Yang S G, Liu Y L, Han Z C. Cardiac potential of stem cells from whole human umbilical cord tissue. J Cell Biochem, 2009, 107(5): 926–932
CrossRef Pubmed Google scholar
[19]
Garcia-Olmo D, Herreros D, Pascual I, Pascual J A, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M. Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum, 2009, 52(1): 79–86
Pubmed
[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): 2277–2286
CrossRef Pubmed Google scholar
[21]
Horwitz E M, Prockop D J, Fitzpatrick L A, Koo W W, 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): 309–313
CrossRef Pubmed Google 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): 804–811
CrossRef Pubmed Google scholar
[23]
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo M E, 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): 1579–1586
CrossRef Pubmed Google scholar
[24]
Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet, 2004, 363(9419): 1439–1441
CrossRef Pubmed Google scholar
[25]
Lee P H, Kim J W, Bang O Y, Ahn Y H, Joo I S, Huh K. Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clin Pharmacol Ther, 2008, 83(5): 723–730
CrossRef Pubmed Google 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): 1407–1416
CrossRef Pubmed Google scholar
[27]
Lin G, Wang G, Liu G, Yang L J, Chang L J, Lue T F, Lin C S. Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev, 2009, 18(10): 1399–1406
CrossRef Pubmed Google scholar
[28]
Liu M, Han Z C. Mesenchymal stem cells: biology and clinical potential in type 1 diabetes therapy. J Cell Mol Med, 2008, 12(4): 1155–1168
CrossRef Pubmed Google scholar
[29]
Santana A, Enseñat-Waser R, Arribas M I, Reig J A, Roche E. Insulin-producing cells derived from stem cells: recent progress and future directions. J Cell Mol Med, 2006, 10(4): 866–883
CrossRef Pubmed Google scholar
[30]
Wang H S, Shyu J F, Shen W S, 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<month>Aug</month><day>18</day>
[31]
Zhang Y, Dou Z. Transdifferentiation of bone marrow mesenchymal stem cell into islet cells to treat diabetes mellitus. J Cell Biol, 2007, 29: 1–5
[32]
Brooke G, Rossetti T, Pelekanos R, Ilic N, Murray P, Hancock S, Antonenas V, Huang G, Gottlieb D, Bradstock K, Atkinson K. Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials. Br J Haematol, 2009, 144(4): 571–579
CrossRef Pubmed Google scholar
[33]
Tran T C, Kimura K, Nagano M, Yamashita T, Ohneda K, Sugimori H, Sato F, Sakakibara Y, Hamada H, Yoshikawa H, Hoang S N, Ohneda O. Identification of human placenta-derived mesenchymal stem cells involved in re-endothelialization. J Cell Physiol, 2011, 226(1): 224–235
CrossRef Pubmed Google scholar
[34]
Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. Stem Cells, 2004, 22(5): 649–658
CrossRef Pubmed Google scholar
[35]
Hwang J H, Shim S S, Seok O S, Lee H Y, Woo S K, Kim B H, Song H R, Lee J K, Park Y K. Comparison of cytokine expression in mesenchymal stem cells from human placenta, cord blood, and bone marrow. J Korean Med Sci, 2009, 24(4): 547–554
CrossRef Pubmed Google 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): 300–311
CrossRef Pubmed Google scholar
[37]
Dzierzak E, Robin C. Placenta as a source of hematopoietic stem cells. Trends Mol Med, 2010, 16(8): 361–367
CrossRef Pubmed Google scholar
[38]
Lee L K, Ueno M, Van Handel B, Mikkola H K. Placenta as a newly identified source of hematopoietic stem cells. Curr Opin Hematol, 2010, 17(4): 313–318
CrossRef Pubmed Google scholar
[39]
Evangelista M, Soncini M, Parolini O. Placenta-derived stem cells: new hope for cell therapy? Cytotechnology, 2008, 58(1): 33–42
CrossRef Pubmed Google scholar
[40]
Zhou J, Ma X J, Bao Y Q, Pan X P, Lu W, Hu C, Xiang K S, Jia W P. Study on prevalence of latent autoimmune diabetes in adults and its relationship with metabolic syndrome. Zhonghua Yi Xue Za Zhi, 2009, 89(18): 1250–1254
Pubmed
[41]
Salem H K, Thiemermann C. Mesenchymal stromal cells: current understanding and clinical status. Stem Cells, 2010, 28(3):585–596
[42]
Phinny D G, Prockop D J. Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair–current views. Stem Cells, 2007, 25(11):2896–2902.
[43]
Horwitz E M, Prather W R. Cytokines as the major mechanism of mesenchymal stem cell clinical activity: expanding the spectrum of cell therapy. Isr Med Assoc J, 2009, 11(4): 209–211
Pubmed

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
AI Summary AI Mindmap
PDF(252 KB)

Accesses

Citations

Detail

Sections
Recommended

/