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Tissue Engineering and Regenerative Medicine

, Volume 15, Issue 6, pp 699–709 | Cite as

Current Status of Stem Cell Treatment for Type I Diabetes Mellitus

  • Anupama Kakkar
  • Ashima Sorout
  • Mahak Tiwari
  • Pallavi Shrivastava
  • Poonam Meena
  • Sumit Kumar Saraswat
  • Supriya Srivastava
  • Rajan Datt
  • Siddharth Pandey
Review Article
  • 67 Downloads

Abstract

BACKGROUND:

Diabetes mellitus is a major health concern in current scenario which has been found to affect people of almost all ages. The disease has huge impact on global health; therefore, alternate methods apart from insulin injection are being explored to cure diabetes. Therefore, this review mainly focuses on the current status and therapeutic potential of stem cells mainly mesenchymal stem cells (MSCs) for Type 1 diabetes mellitus in preclinical animal models as well as humans.

METHODS:

Current treatment for Type 1 diabetes mellitus mainly includes use of insulin which has its own limitations and also the underlying mechanism of diseases is still not explored. Therefore, alternate methods to cure diabetes are being explored. Stem cells are being investigated as an alternative therapy for treatment of various diseases including diabetes. Few preclinical studies have also been conducted using undifferentiated MSCs as well as in vitro MSCs differentiated into β islet cells.

RESULTS:

These stem cell transplant studies have highlighted the benefits of MSCs, which have shown promising results. Few human trials using stem cells have also affirmed the potential of these cells in alleviating the symptoms.

CONCLUSION:

Stem cell transplantation may prove to be a safe and effective treatment for patients with Type 1 diabetes mellitus.

Keywords

Diabetes mellitus Stem cells In vitro differentiation Bone marrow 

Notes

Acknowledgements

The authors are grateful to the Datt Mediproducts Pvt. Ltd. for supporting their current research. We sincerely thank Dr. Rajan Datt for valuable scientific discussion.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interests.

Ethical statement

There are no animal expreiments carried out for this article.

References

  1. 1.
    Zang L, Hao H, Liu J, Li Y, Han W, Mu Y. Mesenchymal stem cell therapy in type 2 diabetes mellitus. Diabetol Metab Syndr. 2017;9:36.PubMedPubMedCentralGoogle Scholar
  2. 2.
    IDF Diabetes Atlas, 5th edition. International Diabetes Federation. 2011. https://www.idf.org/our-activities/advocacy-awareness/resources-and-tools/20:atlas-5th-edition.html.
  3. 3.
    Atkinson MA, Eisenbarth GS. Type I diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358:221–9.PubMedGoogle Scholar
  4. 4.
    DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 1997;5:177–266.Google Scholar
  5. 5.
    You WP, Henneberg M. Type 1 diabetes prevalence increasing globally and regionally: the role of natural selection and life expectancy at birth. BMJ Open Diabetes Res Care. 2016;4:e000161.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Madsen OD. Stem cells and diabetes treatment. APMIS. 2005;113:858–75.PubMedGoogle Scholar
  7. 7.
    Noguchi H. Pancreatic islet transplantation. World J Gastrointest Surg. 2009;1:16–20.PubMedPubMedCentralGoogle Scholar
  8. 8.
    Jamiolkowski RM, Guo LY, Li YR, Shaffer SM, Naji A. Islet Transplantation in Type I Diabetes Mellitus. Yale J Biol Med. 2012;85:37–43.PubMedPubMedCentralGoogle Scholar
  9. 9.
    McCall MD, Toso C, Baetge EE, Shapiro AM. Are stem cells a cure for diabetes? Clin Sci (Lond). 2009;118:87–97.Google Scholar
  10. 10.
    Assady S, Maor G, Amit M, Itskovitz-Eldor J, Skorecki KL, Tzukerman M. Insulin production by human embryonic stem cells. Diabetes. 2001;50:1691–7.PubMedGoogle Scholar
  11. 11.
    Hori Y, Rulifson IC, Tsai BC, Heit JJ, Cahoy JD, Kim SK. Growth inhibitors promote differentiation of insulin-producing tissue from embryonic stem cells. Proc Natl Acad Sci U S A. 2002;99:16105–10.PubMedPubMedCentralGoogle Scholar
  12. 12.
    D’souza N, Rossignoli F, Golinelli G, Grisendi G, Spano C, Candini O, et al. Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies. BMC Med. 2015;13:186.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Sheik Abdulazeez S. Diabetes treatment: a rapid review of the current and future scope of stem cell research. Saudi Pharm J. 2015;23:333–40.Google Scholar
  14. 14.
    Mohanty S, Jain KG, Nandy SB, Kakkar A, Kumar M, Dinda AK, et al. Iron oxide labeling does not affect differentiation potential of human bone marrow mesenchymal stem cells exhibited by their differentiation into cardiac and neuronal cells. Mol Cell Biochem. 2018.  https://doi.org/10.1007/s11010-018-3309-9.CrossRefPubMedGoogle Scholar
  15. 15.
    Hardikar AA, Marcus-Samuels B, Geras-Raaka E, Raaka BM, Gershengorn MC. Human pancreatic precursor cells secrete FGF2 to stimulate clustering into hormone-expressing islet-like cell aggregates. Proc Natl Acad Sci U S A. 2003;100:7117–22.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Gao R, Ustinov J, Pulkkinen MA, Lundin K, Korsgren O, Otonkoski T. Characterization of endocrine progenitor cells and critical factors for their differentiation in human adult pancreatic cell culture. Diabetes. 2003;52:2007–15.Google Scholar
  17. 17.
    Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R. Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science. 2001;292:1389–94.PubMedGoogle Scholar
  18. 18.
    Shiroi A, Yoshikawa M, Yokota H, Fukui H, Ishizaka S, Tatsumi K, et al. Identification of insulin-producing cells derived from embryonic stem cells by zinc-chelating dithizone. Stem Cells. 2002;20:284–92.PubMedGoogle Scholar
  19. 19.
    Kim D, Gu Y, Ishii M, Fujimiya M, Qi M, Nakamura N, et al. In vivo functioning and transplantable mature pancreatic islet-like cell clusters differentiated from embryonic stem cell. Pancreas. 2003;27:e34–41.PubMedGoogle Scholar
  20. 20.
    Deutsch G, Jung J, Zheng M, Lóra J, Zaret KS. A bipotential precursor population for pancreas and liver within the embryonic endoderm. Development. 2001;128:871–81.PubMedGoogle Scholar
  21. 21.
    Yang L, Li S, Hatch H, Ahrens K, Cornelius JG, Petersen BE, et al. In vitro trans-differentiation of adult hepatic stem cells into pancreatic endocrine hormone producing cells. Proc Natl Acad Sci U S A. 2002;99:8078–83.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Kodama S, Kühtreiber W, Fujimura S, Dale EA, Faustman DL. Islet regeneration during the reversal of autoimmune diabetes in NOD mice. Science. 2003;302:1223–7.PubMedGoogle Scholar
  23. 23.
    Vishnubalaji R, Al-Nbaheen M, Kadalmani B, Aldahmash A, Ramesh T. Skin-derived multipotent stromal cells—an archrival for mesenchymal stem cells. Cell Tissue Res. 2012;350:1–12.PubMedGoogle Scholar
  24. 24.
    Al-Nbaheen M, Vishnubalaji R, Ali D, Bouslimi A, Al-Jassir F, Megges M, et al. Human stromal (mesenchymal) stem cells from bone marrow, adipose tissue and skin exhibit differences in molecular phenotype and differentiation potential. Stem Cell Rev. 2013;9:32–43.PubMedGoogle Scholar
  25. 25.
    Meirelles Lda S, Nardi NB. Methodology, biology and clinical applications of mesenchymal stem cells. Front Biosci (Landmark Ed). 2009;14:4281–98.Google Scholar
  26. 26.
    Erices A, Conget P, Minguell JJ. Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol. 2000;109:235–42.PubMedGoogle Scholar
  27. 27.
    Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, et al. Stem cell properties of human dental pulp stem cells. J Dent Res. 2002;81:531–5.PubMedGoogle Scholar
  28. 28.
    Najafzadeh N, Esmaeilzade B, Dastan Imcheh M. Hair follicle stem cells: in vitro and in vivo neural differentiation. World J Stem Cells. 2015;7:866–72.PubMedPubMedCentralGoogle Scholar
  29. 29.
    Baer PC, Geiger H. Adipose-derived mesenchymal stromal/stem cells: tissue localization, characterization, and heterogeneity. Stem Cells Int. 2012;2012:812693.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315–7.PubMedGoogle Scholar
  31. 31.
    Friedenstein AJ, Gorskaja JF, Kulagina NN. Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol. 1976;4:267–74.PubMedGoogle Scholar
  32. 32.
    Horwitz EM, Dominici M. How do mesenchymal stromal cells exert their therapeutic benefit? Cytotherapy. 2008;10:771–4.PubMedGoogle Scholar
  33. 33.
    Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, et al. Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol. 2006;111:231–9.PubMedGoogle Scholar
  34. 34.
    Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010;28:1099–106.PubMedGoogle Scholar
  35. 35.
    Estrada EJ, Valacchi F, Nicora E, Brieva S, Esteve C, Echevarria L, et al. Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus. Cell Transplant. 2008;17:1295–304.PubMedGoogle Scholar
  36. 36.
    Kang SK, Shin MJ, Jung JS, Kim YG, Kim CH. Autologous adipose tissue-derived stromal cells for treatment of spinal cord injury. Stem Cells Dev. 2006;15:583–94.PubMedGoogle Scholar
  37. 37.
    Cheng SK, Park EY, Pehar A, Rooney AC, Gallicano GI. Current progress of human trials using stem cell therapy as a treatment for diabetes mellitus. Am J Stem Cells. 2016;5:74–86.PubMedPubMedCentralGoogle Scholar
  38. 38.
    Kao SY, Shyu JF, Wang HS, Lin CH, Su CH, Chen TH, et al. Comparisons of differentiation potential in human mesenchymal stem cells from Wharton’s jelly, bone marrow, and pancreatic tissues. Stem Cells Int. 2015;2015:306158.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Oh SH, Muzzonigro TM, Bae SH, LaPlante JM, Hatch HM, Petersen BE. Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes. Lab Invest. 2004;84:607–17.PubMedGoogle Scholar
  40. 40.
    Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol. 2004;10:3016–20.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, et al. In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes. 2004;53:1721–32.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Abouzaripour M, Pasbakhsh P, Atlasi N, Shahverdi AH, Mahmoudi R, Kashani IR. In vitro differentiation of insulin secreting cells from mouse bone marrow derived stage-specific embryonic antigen 1 positive stem cells. Cell J. 2016;17:701–10.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Paz AH, Salton GD, Ayala-Lugo A, Gomes C, Terraciano P, Scalco R, et al. Betacellulin overexpression in mesenchymal stem cells induces insulin secretion in vitro and ameliorates streptozotocin-induced hyperglycemia in rats. Stem Cells Dev. 2011;20:223–32.PubMedGoogle Scholar
  44. 44.
    Gabr MM, Sobh MM, Zakaria MM, Refaie AF, Ghoneim MA. Transplantation of insulin-producing clusters derived from adult bone marrow stem cells to treat diabetes in rats. Exp Clin Transplant. 2008;6:236–43.PubMedGoogle Scholar
  45. 45.
    Zanini C, Bruno S, Mandili G, Baci D, Cerutti F, Cenacchi G, et al. Differentiation of mesenchymal stem cells derived from pancreatic islets and bone marrow into islet-like cell phenotype. PLoS One. 2011;6:e28175.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Gerace D, Martiniello-Wilks R, Nassif NT, Lal S, Steptoe R, Simpson AM. CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success? Stem Cell Res Ther. 2017;8:62.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells. 2007;25:2837–44.PubMedGoogle Scholar
  48. 48.
    Bassi ÊJ, Moraes-Vieira PM, Moreira-Sá CS, Almeida DC, Vieira LM, Cunha CS, et al. Immune regulatory properties of allogeneic adipose-derived mesenchymal stem cells in the treatment of experimental autoimmune diabetes. Diabetes. 2012;61:2534–45.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Klinker MW, Wei CH. Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models. World J Stem Cells. 2015;7:556–67.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Lin G, Wang G, Liu G, Yang LJ, Chang LJ, Lue TF, et al. Treatment of type 1 diabetes with adipose tissue-derived stem cells expressing pancreatic duodenal homeobox 1. Stem Cells Dev. 2009;18:1399–406.PubMedPubMedCentralGoogle Scholar
  51. 51.
    De Ugarte DA, Alfonso Z, Zuk PA, Elbarbary A, Zhu M, Ashjian P, et al. Differential expression of stem cell mobilization associated-molecules on multi lineage cells from adipose tissue and bone marrow. Immunol Lett. 2003;89:267–70.PubMedGoogle Scholar
  52. 52.
    Timper K, Seboek D, Eberhardt M, Linscheid P, Christ-Crain M, Keller U, et al. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells. Biochem Biophys Res Commun. 2006;341:1135–40.PubMedGoogle Scholar
  53. 53.
    Dave SD, Vanikar AV, Trivedi HL. Extrinsic factors promoting in vitro differentiation of insulin-secreting cells from human adipose tissue-derived mesenchymal stem cells. Appl Biochem Biotechnol. 2013;170:962–71.PubMedGoogle Scholar
  54. 54.
    Li J, Zhu L, Qu X, Li J, Lin R, Liao L, et al. Stepwise differentiation of human adipose-derived mesenchymal stem cells toward definitive endoderm and pancreatic progenitor cells by mimicking pancreatic development in vivo. Stem Cells Dev. 2013;22:1576–87.PubMedGoogle Scholar
  55. 55.
    Trivedi HL, Vanikar AV, Thakker U, Firoze A, Dave SD, Patel CN, et al. Human adipose tissue-derived mesenchymal stem cells combined with hematopoietic stem cell transplantation synthesize insulin. Transplant Proc. 2008;40:1135–9.PubMedGoogle Scholar
  56. 56.
    Marappagounder D, Somasundaram I, Dorairaj S, Sankaran RJ. Differentiation of mesenchymal stem cells derived from human bone marrow and subcutaneous adipose tissue into pancreatic islet-like clusters in vitro. Cell Mol Biol Lett. 2013;18:75–88.PubMedGoogle Scholar
  57. 57.
    Kajiyama H, Hamazaki TS, Tokuhara M, Masui S, Okabayashi K, Ohnuma K, et al. Pdx1-transfected adipose tissue-derived stem cells differentiate into insulin-producing cells in vivo and reduce hyperglycemia in diabetic mice. Int J Dev Biol. 2010;54:699–705.PubMedGoogle Scholar
  58. 58.
    Kadam S, Muthyala S, Nair P, Bhonde R. Human placenta-derived mesenchymal stem cells and islet-like cell clusters generated from these cells as a novel source for stem cell therapy in diabetes. Rev Diabet Stud. 2010;7:168–82.PubMedPubMedCentralGoogle Scholar
  59. 59.
    Sun NZ, Ji HS. In vitro differentiation of human placenta-derived adherent cells into insulin-producing cells. J Int Med Res. 2009;37:400–6.PubMedGoogle Scholar
  60. 60.
    Gao F, Wu DQ, Hu YH, Jin GX, Li GD, Sun TW, et al. In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res. 2008;151:293–302.PubMedGoogle Scholar
  61. 61.
    Harris DT, Rogers I. Umbilical cord blood: a unique source of pluripotent stem cells for regenerative medicine. Curr Stem Cell Res Ther. 2007;2:301–9.PubMedGoogle Scholar
  62. 62.
    Pessina A, Eletti B, Croera C, Savalli N, Diodovich C, Gribaldo L. Pancreas developing markers expressed on human mononucleated umbilical cord blood cells. Biochem Biophys Res Commun. 2004;323:315–22.PubMedGoogle Scholar
  63. 63.
    Sun B, Roh KH, Lee SR, Lee YS, Kang KS. Induction of human umbilical cord blood-derived stem cells with embryonic stem cell phenotypes into insulin producing islet-like structure. Biochem Biophys Res Commun. 2007;354:919–23.PubMedGoogle Scholar
  64. 64.
    Gao F, Wu DQ, Hu YH, Jin GX. Extracellular matrix gel is necessary for in vitro cultivation of insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Chin Med J (Engl). 2008;121:811–8.Google Scholar
  65. 65.
    Polgár K, Adány R, Abel G, Kappelmayer J, Muszbek L, Papp Z. Characterization of rapidly adhering amniotic fluid cells by combined immunofluorescence and phagocytosis assays. Am J Hum Genet. 1989;45:786–92.PubMedPubMedCentralGoogle Scholar
  66. 66.
    Priest RE, Marimuthu KM, Priest JH. Origin of cells in human amniotic fluid cultures: ultrastructural features. Lab Invest. 1978;39:106–9.PubMedGoogle Scholar
  67. 67.
    Trovato L, De Fazio R, Annunziata M, Sdei S, Favaro E, Ponti R, et al. Pluripotent stem cells isolated from human amniotic fluid and differentiation into pancreatic beta-cells. J Endocrinol Invest. 2009;32:873–6.PubMedGoogle Scholar
  68. 68.
    Ezquer F, Ezquer M, Contador D, Ricca M, Simon V, Conget P. The antidiabetic effect of mesenchymal stem cells is unrelated to their transdifferentiation potential but to their capability to restore Th1/Th2 balance and to modify the pancreatic microenvironment. Stem Cells. 2012;30:1664–74.PubMedGoogle Scholar
  69. 69.
    Sordi V, Malosio ML, Marchesi F, Mercalli A, Melzi R, Giordano T, et al. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets. Blood. 2005;106:419–27.PubMedGoogle Scholar
  70. 70.
    Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, et al. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci U S A. 2006;103:17438–43.PubMedPubMedCentralGoogle Scholar
  71. 71.
    Bell GI, Broughton HC, Levac KD, Allan DA, Xenocostas A, Hess DA. Transplanted human bone marrow progenitor subtypes stimulate endogenous islet regeneration and revascularization. Stem Cells Dev. 2012;21:97–109.PubMedGoogle Scholar
  72. 72.
    Ezquer FE, Ezquer ME, Parrau DB, Carpio D, Yañez AJ, Conget PA. Systemic administration of multipotent mesenchymal stromal cells reverts hyperglycemia and prevents nephropathy in type I diabetic mice. Biol Blood Marrow Transplant. 2008;14:631–40.PubMedGoogle Scholar
  73. 73.
    Davis NE, Hamilton D, Fontaine MJ. Harnessing the immunomodulatory and tissue repair properties of mesenchymal stem cells to restore β cell function. Curr Diab Rep. 2012;12:612–22.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Jurewicz M, Yang S, Augello A, Godwin JG, Moore RF, Azzi J, et al. Congenic mesenchymal stem cell therapy reverses hyperglycemia in experimental type 1 diabetes. Diabetes. 2010;59:3139–47.PubMedPubMedCentralGoogle Scholar
  75. 75.
    Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57:1759–67.PubMedPubMedCentralGoogle Scholar
  76. 76.
    Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, et al. Mesenchymal stem cells: mechanisms of immunomodulation and homing. Cell Transplant. 2010;19:667–79.PubMedPubMedCentralGoogle Scholar
  77. 77.
    Carlsson PO, Schwarcz E, Korsgren O, Le Blanc K. Preserved beta-cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes. 2015;64:587–92.PubMedGoogle Scholar
  78. 78.
    Cai J, Wu Z, Xu X, Liao L, Chen J, Huang L, et al. Umbilical cord mesenchymal stromal cell with autologous bone marrow cell transplantation in established type 1 diabetes: a pilot randomized controlled open-label clinical study to assess safety and impact on insulin secretion. Diabetes Care. 2016;39:149–57.PubMedGoogle Scholar
  79. 79.
    Hu J, Yu X, Wang Z, Wang F, Wang L, Gao H, et al. Long term effects of the implantation of Wharton’s jelly-derived mesenchymal stem cells from the umbilical cord for newly-onset type 1 diabetes mellitus. Endocr J. 2013;60:347–57.PubMedGoogle Scholar
  80. 80.
    Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012;12:517–23.PubMedGoogle Scholar
  81. 81.
    Zhao Y, Jiang Z, Zhao T, et al. Reversal of type 1 diabetes via islet beta cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012;10:3.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Delgado E, Perez-Basterrechea M, Suarez-Alvarez B, Zhou H, Revuelta EM, Garcia-Gala JM, et al. Modulation of autoimmune T-cell memory by stem cell educator therapy: phase 1/2 clinical trial. EBioMedicine. 2015;2:2024–36.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin. 2013;34:747–54.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Chhabra P, Brayman KL. Stem cell therapy to cure type 1 diabetes: from hype to hope. Stem Cells Transl Med. 2013;2:328–36.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Prabakar KR, Dominguez-Bendala J, Molano RD, Pileggi A, Villate S, Ricordi C, et al. Generation of glucose-sensitive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplant. 2012;21:1321–39.PubMedGoogle Scholar
  86. 86.
    Uccelli A, Pistoia V, Moretta L. Mesenchymal stem cells: a new strategy for immunosuppression? Trends Immunol. 2007;28:219–26.PubMedGoogle Scholar
  87. 87.
    Keating A. Mesenchymal stromal cells. Curr Opin Hematol. 2006;13:419–25.PubMedGoogle Scholar
  88. 88.
    Prockop DJ. “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin Pharmacol Ther. 2007;82:241–3.PubMedGoogle Scholar
  89. 89.
    Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000;28:875–84.PubMedGoogle Scholar
  90. 90.
    Dazzi F, Horwood NJ. Potential of mesenchymal stem cell therapy. Curr Opin Oncol. 2007;19:650–5.PubMedGoogle Scholar
  91. 91.
    Kaviani M, Negar Azarpira N. Insight into microenvironment remodeling in pancreatic endocrine tissue engineering: biological and biomaterial approaches. Tissue Eng Regen Med. 2016;13:475–84.Google Scholar
  92. 92.
    Uccelli A, Moretta L, Pistoia V. Immunoregulatory function of mesenchymal stem cells. Eur J Immunol. 2006;36:2566–73.PubMedGoogle Scholar
  93. 93.
    Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, et al. 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;54:2277–86.PubMedPubMedCentralGoogle Scholar
  94. 94.
    Huang XP, Sun Z, Miyagi Y, McDonald Kinkaid H, Zhang L, Weisel RD, et al. Differentiation of allogeneic mesenchymal stem cells induces immunogenicity and limits their long term benefits for myocardial repair. Circulation. 2010;122:2419–29.PubMedGoogle Scholar

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Anupama Kakkar
    • 1
  • Ashima Sorout
    • 1
  • Mahak Tiwari
    • 1
  • Pallavi Shrivastava
    • 1
  • Poonam Meena
    • 1
  • Sumit Kumar Saraswat
    • 1
  • Supriya Srivastava
    • 1
  • Rajan Datt
    • 2
  • Siddharth Pandey
    • 1
  1. 1.Department of Life Sciences (R&D)Datt Mediproducts Pvt. Ltd.District MewatIndia
  2. 2.Datt Mediproducts Pvt Ltd.New DelhiIndia

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