Feto-Maternal Mesenchymal Stem Cell Transplantation for Treating Diabetes

  • Ramesh R. Bhonde
  • Vijayalakshmi Venkatesan


In recent years, stem cells have reached to greater heights due to its therapeutic potential in treating degenerative diseases. The long-term objective of regenerative medicine or stem cell therapy is to treat patients with their own stem cells. A better understanding of stem cell biology would almost certainly allow for the establishment of efficient and reliable cell transplantation experimental programs in the clinic. These stem cells can be isolated from various sources such as the bone marrow, adipose tissue, pancreas, liver, placenta, umbilical cord blood, Wharton’s jelly, and so on. However, the present investigation demands a readily available, abundant, reliable noninvasive, and efficient source of stem cell that could be a valuable tool in regenerative medicine. Such sources that could be explored in the aforesaid category are the feto-maternal mesenchymal stem cells (biological trash) such as placenta, cord blood, and cord tissue. These could be transformed into a treasure in treatment of multitude of diseases, especially in the treatment of diabetes.


Stem Cell Umbilical Cord Umbilical Cord Blood Mesenchymal Stromal Cell Amniotic Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Evangelista M, Soncini M, Parolini O et al (2008) Placenta derived stem cells, new hope for cell therapy? Cytotechnology 58:33–42PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Blanco O, Leno-Duran E, Morales JC, Olivares EG, Ruiz-Ruiz C et al (2009) Human decidual stromal cells protect lymphocytes from apoptosis. Placenta 30:677–685PubMedCrossRefGoogle Scholar
  3. 3.
    Witkowska-Zimny M, Wróbel E et al (2011) Perinatal sources of mesenchymal stem cells: Wharton’s jelly, amnion and chorion. Cell Mol Biol Lett 16:493–514PubMedCrossRefGoogle Scholar
  4. 4.
    Indumathi S et al (2013) Comparison of feto-maternal organ derived stem cells in facets of immunophenotype, proliferation and differentiation. Tissue Cell 45(6):434–442PubMedCrossRefGoogle Scholar
  5. 5.
    Kadam SS, Sudhakar M, Nair PD, Bhonde RR (2010) Reversal of experimental diabetes in mice by transplantation of neo-islets generated from human amnion-derived mesenchymal stromal cells using immuno-isolatory macrocapsules. Cytotherapy 12:982–991PubMedCrossRefGoogle Scholar
  6. 6.
    Sabapathy V, Ravi S, Srivastava V, Srivastava A, Kumar S (2012) Long term cultured human term placenta-derived mesenchymal stem cells of maternal origin displays plasticity. Stem Cells Int 419. doi: 10.1155/2012/174328
  7. 7.
    Ilancheran S, Michalska A, Peh G, Wallace EM, Pera M, Manuelpillai U et al (2007) Stem cells derived from human fetal membranes display multi-lineage differentiation potential. Biol Reprod 77:577–588PubMedCrossRefGoogle Scholar
  8. 8.
    Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ et al (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337PubMedCrossRefGoogle Scholar
  9. 9.
    Roura S, Bago’ JR, Soler-Botija C, Pujal JM, Ga’lvez-Monto’n C et al (2012) Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo. PLoS One 7(11):e49447PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Nascimento DS, Mosqueira D, Sousa LM, Teixeira M et al (2014) Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodelling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms. Stem Cell Res Ther 5:5PubMedCentralCrossRefGoogle Scholar
  11. 11.
    Lim JY, Jeong CH, Jun JA, Kim SM, Ryu CH et al (2011) Therapeutic effects of human umbilical cord blood-derived mesenchymal stem cells after intrathecal administration by lumbar puncture in a rat model of cerebral ischemia. Stem Cell Res Ther 2(5):38PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Jiao H, Guan F, Yang B, Li J, Shan H, Song L et al (2011) Human umbilical cord blood-derived mesenchymal stem cells inhibit C6 glioma via downregulation of cyclin D1. Neurol India 59(2):241–247PubMedCrossRefGoogle Scholar
  13. 13.
    Parekh VS, Joglekar MV, Hardikar AA (2009) Differentiation of human umbilical cord blood-derived mononuclear cells to endocrine pancreatic lineage. Differentiation 78(4):232–240PubMedCrossRefGoogle Scholar
  14. 14.
    Lee EJ, Choi EK, Kang SK, Kim GH, Park JY et al (2012) N-cadherin determines individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in a rat model of myocardial infarction. Mol Ther 20(1):155–167PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Yen BL, Huang HI, Chien CC, Jui HY, Ko BS et al (2005) Isolation of multipotent cells from human term placenta. Stem Cells 23:3–9PubMedCrossRefGoogle Scholar
  16. 16.
    Kadam S, Muthyala S, Nair P, Bhonde R (2010) 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 7:168–182PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Kadam SS, Bhonde RR (2010) Islet neogenesis from the constitutively nestin expressing human umbilical cord matrix derived mesenchymal stem cells. Islets 2:112–120PubMedCrossRefGoogle Scholar
  18. 18.
    Malgieri A, Kantzari E, Patrizi MP, Gambardella S (2010) Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med 3(4):248–269PubMedCentralPubMedGoogle Scholar
  19. 19.
    Chen G, Yue A, Ruan Z, Yin Y, Wang R et al (2014) Monitoring the biology stability of human umbilical cord-derived mesenchymal stem cells during long-term culture in serum-free medium. Cell Tissue Bank. doi: 10.1007/s10561-014-9420-6
  20. 20.
    Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E et al (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343(4):230–238PubMedCrossRefGoogle Scholar
  21. 21.
    Shapiro AM, Ricordi C, Hering BJ, Auchincloss H, Lindblad R et al (2006) International trial of the Edmonton protocol for islet transplantation. N Engl J Med 355(13):1318–1330PubMedCrossRefGoogle Scholar
  22. 22.
    Couri CE, Voltarelli JC (2011) Stem cell based therapies and immunomodulatory approaches in newly diagnosed type 1 diabetes. Curr Stem Cell Res Ther 6(1):10–15PubMedCrossRefGoogle Scholar
  23. 23.
    Liew CG (2010) Generation of insulin producing cells from pluripotent stem cells: from the selection of cell sources to the optimization of protocols. Rev Diabet Stud 7(2):82–92PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Hebrok M (2012) Generating Beta cells from stem cells-the story so far. Cold Spring Harb Perspect Med 2(6):a007674PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872PubMedCrossRefGoogle Scholar
  26. 26.
    Bhonde RR, Sheshadri P, Sharma S, Kumar A (2014) Making surrogate β-cells from mesenchymal stromal cells: perspectives and future endeavors. Int J Biochem Cell Biol 46:90–102PubMedCrossRefGoogle Scholar
  27. 27.
    Zhao Y, Mazzone T (2010) Human cord blood stem cells and the journey to a cure for type 1 diabetes. Autoimmun Rev 10(2):103–107PubMedCrossRefGoogle Scholar
  28. 28.
    Fukuchi Y, Nakajima H, Sugiyama D, Hirose I, Kitamura T, Tsuji K (2004) Human placental derived cells have mesenchymal stem/progenitor cell potential. Stem Cells 22(5):649–658PubMedCrossRefGoogle Scholar
  29. 29.
    Murphy SV, Atala A (2013) Amniotic Fluid and placental membranes: unexpected sources of highly multipotent cells. Semin Reprod Med 31(1):62–68PubMedCrossRefGoogle Scholar
  30. 30.
    Bhaumick B, Danilkewich AD, Bala RM (1988) Altered placental insulin and insulin-like growth factor-I receptors in diabetes. Life Sci 42(17):1603–1614PubMedCrossRefGoogle Scholar
  31. 31.
    Giddings SJ, Carnaghi L (1989) Rat insulin II gene expression by extraplacental membranes. A non-pancreatic source for fetal insulin. J Biol Chem 264(16):9462–9469PubMedGoogle Scholar
  32. 32.
    Desoye G, Hauguel-de Mouzon S (2007) The human placenta in gestational diabetes mellitus. The insulin and cytokine network. Diabetes Care 30 Suppl 2:S120–S126PubMedCrossRefGoogle Scholar
  33. 33.
    Han VK, Carter AM (2000) Spatial and temporal patterns of expression of messenger RNA for insulin-like growth factors and their binding proteins in the placenta of man and laboratory animals. Placenta 21(4):289–305PubMedCrossRefGoogle Scholar
  34. 34.
    Priest RE, Marimuthu KM, Priest JH (1978) Origin of cells in human amniotic fluid cultures: ultrastructural features. Lab Invest 39(2):106–109PubMedGoogle Scholar
  35. 35.
    Pappa KI, Anagnou NP (2009) Novel sources of fetal stem cells: where do they fit on the developmental continuum? Regen Med 4(3):423–433PubMedCrossRefGoogle Scholar
  36. 36.
    De Coppi P, Bartsch G Jr, Siddiqui MM et al (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106PubMedCrossRefGoogle Scholar
  37. 37.
    Kaviani A, Perry TE, Dzakovic A, Jennings RW, Ziegler MM, Fauza DO (2001) The amniotic fluid as a source of cells for fetal tissue engineering. J Pediatr Surg 36:1662–1665PubMedCrossRefGoogle Scholar
  38. 38.
    Liu Y, Cao D-L, Guo L-B, Guo S-N, Xu J-K et al (2013) Amniotic stem cell transplantation therapy for type 1 diabetes: a case report. J Int Med Res 41:1370PubMedCrossRefGoogle Scholar
  39. 39.
    Villani V, Milanesi A, Sedrakyan S, Da Sacco S, Angelow S et al (2014) Amniotic fluid stem cells prevent β-cell injury. Cytotherapy 16(1):41–55PubMedCrossRefGoogle Scholar
  40. 40.
    Zulewski H, Abraham EJ, Gerlach MJ, Daniel PB et al (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50(3):521–533PubMedCrossRefGoogle Scholar
  41. 41.
    Montesinos JJ, Flores-Figueroa E, Castillo-Medina S, Flores-Guzman P, Hernadez-Estevez E, Fajardo-orduna G et al (2009) Human mesenchymal stromal cells from adult and neonatal sources: comparative analysis of their morphology, immunophenotype, differentiation patterns and neural protein expression. Cytotherapy 11(2):163–176PubMedCrossRefGoogle Scholar
  42. 42.
    Romanov YA, Svintsitskaya VA, Smirnov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC like cells from umbilical cord. Stem Cells 21:105–110PubMedCrossRefGoogle Scholar
  43. 43.
    Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S et al (2006) Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 24(3):781–792PubMedCrossRefGoogle Scholar
  44. 44.
    Gao F, Wu DQ, Hu YH et al (2008) In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res 151(6):293–302PubMedCrossRefGoogle Scholar
  45. 45.
    Prabhakar KR, Domiguez-Bendala J, Molano RD, Pileggi A, Villate S, Ricordi C et al (2012) Generation of glucose responsive, insulin producing cells from human umbilical cord blood derived mesenchymal stem cells. Cell Transplant 21(6):1321–1339CrossRefGoogle Scholar
  46. 46.
    Chao KC, Chao KF, Fu YS, Liu SH (2008) Islet-like clusters derived from mesenchymal stem cells in Wharton’s jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One 3(1):e1451PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Prasanna SJ, Jahnavi VS (2011) Wharton’s jelly mesenchymal stem cells as off the shelf cellular therapeutics: a closer link into closer into their regenerative and immunomodulatory properties. Open Tissue Eng Regen Med J 4:28–38CrossRefGoogle Scholar
  48. 48.
    Anzalone R, Farina F, Zummo G et al (2011) Recent patents and advances on isolation and cellular therapy applications of mesenchymal stem cells from human umbilical cord Wharton’s jelly. Recent Patents Regen Med 1:216–227CrossRefGoogle Scholar
  49. 49.
    Wang HS, Shyu JF, Shen WS, Hsu HC, Chi TC et al (2011) Transplantation of insulin producing cells derived from umbilical cord stromal mesenchymal stem cells to treat NOD mice. Cell Transplant 20(3):455–466PubMedCrossRefGoogle Scholar
  50. 50.
    Ying Hu, Jun Liang, Hongping Cui, Xinmei Wang, Hua Rong et al (2013) Wharton’s jelly mesenchymal stem cells differentiate into retinal progenitor cells. Neural Regen Res 8:1783–1792PubMedCentralPubMedGoogle Scholar
  51. 51.
    Vaziri H, Dragowska W, Allsopp RC, Thomas TE, Harley CB et al (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc Natl Acad Sci U S A 91(21):9857–9860PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Pessina A, Eletti B, Croera C et al (2004) Pancreas developing markers expressed on human mononucleated umbilical cord blood cells. Biochem Biophys Res Commun 323(1):315–322PubMedCrossRefGoogle Scholar
  53. 53.
    Prabakar KR, Domínguez-Bendala J, Molano RD, Pileggi A, Villate S et al (2012) Generation of glucose-responsive, insulin-producing cells from human umbilical cord blood-derived mesenchymal stem cells. Cell Transplant 21(6):1321–1339PubMedCrossRefGoogle Scholar
  54. 54.
    Yoshida S, Ishikawa F, Kawano N, Shimoda K, Nagafuchi S, Shimoda S et al (2005) Human cord blood derived cells generate insulin producing cells in vivo. Stem Cells 23(9):1409–1416PubMedCrossRefGoogle Scholar
  55. 55.
    Harris DT, Rogers I (2007) Umbilical cord blood: a unique source of pluripotent stem cells for regenerative medicine. Curr Stem Cell Res Ther 2(4):301–309PubMedCrossRefGoogle Scholar
  56. 56.
    Zhao Y, Huang Z, Qi M, Lazzarani P, Mazzone T (2007) Immune regulation of T lymphocyte by a newly characterized human umbilical cord blood stem cell. Immunol Lett 108(1):78–87PubMedCrossRefGoogle Scholar
  57. 57.
    Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH (2008) Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes 57(7):1759–1767PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Ucceli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8(9):726–736CrossRefGoogle Scholar
  59. 59.
    Zhao Y, Lin B, Darflinger R, Zhang Y, Holterman MJ, Skidgel RA (2009) Human cord blood stem cell modulated regulatory T lymphocytes reverse the autoimmune caused type 1 diabetes in non obese diabetic mice. PLoS One 4(1):e4226PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Aguayo-Mazzucato C, Bonner-Weir S (2010) Stem cell therapy for type 1 diabetes mellitus. Nat Rev Endocrinol 6(3):139–148PubMedCrossRefGoogle Scholar
  61. 61.
    Phadnis SM, Joglekar MV, Dalvi MP et al (2011) Human bone marrow-derived mesenchymal cells differentiate and mature into endocrine pancreatic lineage in vivo. Cytotherapy 13(3):279–293PubMedCrossRefGoogle Scholar
  62. 62.
    Domínguez-Bendala J, Lanzoni G, Inverardi L, Ricordi C (2012) Concise review: mesenchymal stem cells for diabetes. Stem Cells Trans Med 1:59–63CrossRefGoogle Scholar

Copyright information

© Springer India 2014

Authors and Affiliations

  1. 1.School of Regenerative MedicineManipal Institute of Regenerative Medicine, Manipal UniversityBangaloreIndia
  2. 2.Department of Stem Cell ResearchNational Institute of Nutrition (ICMR)Secunderabad, HyderabadIndia

Personalised recommendations