Current Understanding Realities of Umbilical Cord Stem Cells Biology and Future Perspectives in Clinical Application

  • Somayeh Ebrahimi-BaroughEmail author
  • Reza Rahbarghazi
  • Zohreh Bagher
  • Jafar Ai
  • Elham Hoveizi
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)


In the recent years from variety of tissues, stem cells have been isolated but seem to be more concerning to mesenchymal stem cells (MSCs). Mesenchymal stem cells (MSCs) from bone marrow, adult organs, and fetuses show the disadvantages of ethical constraints, invasive isolation, and low cell numbers, and there are the clinical hurdles of potential immunorejection and tumorigenesis in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), respectively. To overcome these limitations, the potential of fetal stem cells derived from birth-associated tissues has been investigated. Mesenchymal stem cells have also been reported in some compartments of the umbilical cord (UC-MSCs) including umbilical blood vessel adventia and endothelium, amnion, subamnion, Wharton’s jelly, perivascular region. UC-MSCs are noncontroversial and ease of sourcing cells. These cells can be harvested painlessly in abundance and have higher rate of proliferation, possess stemness properties, differentiation abilities, immunosuppressive, and do not induce teratomas and have anticancer properties. These advantages make them ideal for their use in cell-based therapies and treatment of cancers. In this chapter, we will at first give an overview of the biology and phenotypic characteristics, then provide an outline of the recent findings related to UC-MSC therapeutic application for the treatment of malignant and nonmalignant hematopoietic and nonhematopoietic diseases.


Umbilical cord compartments Mesenchymal stem cell Wharton’s jelly Phenotypic characteristics Therapeutic application 


  1. Aali E, Mirzamohammadi S, Ghaznavi H, Madjd Z, Larijani B, Rayegan S, Sharifi AM (2014) A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats. J Diabetes Metab Disord 13(1):76PubMedPubMedCentralCrossRefGoogle Scholar
  2. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4):1815–1822PubMedCrossRefGoogle Scholar
  3. Alt EU, Senst C, Murthy SN, Slakey DP, Dupin CL, Chaffin AE, Kadowitz PJ, Izadpanah R (2012) Aging alters tissue resident mesenchymal stem cell properties. Stem Cell Res 8(2):215–225PubMedCrossRefGoogle Scholar
  4. Appelbaum FR (2012) Pursuing the goal of a donor for everyone in need. N Engl J Med 367(16):1555PubMedCrossRefGoogle Scholar
  5. Artene S-A, Ciurea ME, Purcaru SO, Tache DE, Tataranu LG, Lupu M, Dricu A (2013) Biobanking in a constantly developing medical world. Scientific World Journal 2013:343275PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bagher Z, Ebrahimi-Barough S, Azami M, Mirzadeh H, Soleimani M, Ai J, Nourani MR, Joghataei MT (2015) Induction of human umbilical Wharton’s jelly-derived mesenchymal stem cells toward motor neuron-like cells. In Vitro Cell Dev Biol Anim 51(9):987–994. doi: 10.1007/s11626-015-9921-z PubMedCrossRefGoogle Scholar
  7. Bagher Z, Azami M, Ebrahimi-Barough S, Mirzadeh H, Solouk A, Soleimani M, Ai J, Nourani MR, Joghataei MT (2016a) Differentiation of Wharton’s jelly-derived mesenchymal stem cells into motor neuron-like cells on three-dimensional collagen-grafted nanofibers. Mol Neurobiol 53(4):2397–2408. doi: 10.1007/s12035-015-9199-x PubMedCrossRefGoogle Scholar
  8. Bagher Z, Ebrahimi-Barough S, Azami M, Safa M, Joghataei MT (2016b) Cellular activity of Wharton’s Jelly-derived mesenchymal stem cells on electrospun fibrous and solvent-cast film scaffolds. J Biomed Mater Res A 104(1):218–226. doi: 10.1002/jbm.a.35555 PubMedCrossRefGoogle Scholar
  9. Bakhshi T, Zabriskie RC, Bodie S, Kidd S, Ramin S, Paganessi LA, Gregory SA, Fung HC, Christopherson KW 2nd (2008) Mesenchymal stem cells from the Wharton’s jelly of umbilical cord segments provide stromal support for the maintenance of cord blood hematopoietic stem cells during long-term ex vivo culture. Transfusion 48(12):2638–2644PubMedPubMedCentralCrossRefGoogle Scholar
  10. Baksh D, Yao R, Tuan RS (2007) Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25:1384–1392PubMedCrossRefGoogle Scholar
  11. Ballen K (2010) Challenges in umbilical cord blood stem cell banking for stem cell reviews and reports. Stem Cell Rev Rep 6:8–14CrossRefGoogle Scholar
  12. Ballen KK, Gluckman E, Broxmeyer HE (2013) Umbilical cord blood transplantation: the first 25 years and beyond. Blood 122(4):491–498PubMedPubMedCentralCrossRefGoogle Scholar
  13. Barry FP, Murphy JM, English K, Mahon BP (2005) Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft. Stem Cells Dev 14:252–265PubMedCrossRefGoogle Scholar
  14. Batsali AK, Kastrinaki M, Papadaki HA, Pontikoglou C (2013) Mesenchymal stem cells derived from Wharton’s jelly of the umbilical cord: biological properties and emerging clinical applications. Curr Stem Cell Res Ther 8:144–155PubMedCrossRefGoogle Scholar
  15. Bauder AR, Ferguson TA (2012) Reproducible mouse sciatic nerve crush and subsequent assessment of regeneration by whole mount muscle analysis. J Vis Exp (60). doi: 10.3791/3606
  16. Berezin AE (2014) Diabetes mellitus and cellular replacement therapy: expected clinical potential and perspectives. World J Diabetes 5(6):777PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bongso A, Fong CY (2013) The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton’s jelly of the human umbilical cord. Stem Cell Rev 9:226–240PubMedCrossRefGoogle Scholar
  18. Bongso A, Fong CY, Ng SC, Ratnam S (1994) Isolation and culture of inner cell mass cells from human blastocysts. Hum Reprod 9:2110–2117PubMedGoogle Scholar
  19. Borhani-Haghighi M, Talaei-Khozani T, Ayatollahi M, Vojdani Z (2015) Wharton’s Jelly-derived mesenchymal stem cells can differentiate into hepatocyte-like cells by HepG2 cell line extract. Iran J Med Sci 40(2):143–151PubMedPubMedCentralGoogle Scholar
  20. Broxmeyer HE, Douglas GW, Hangoc G, Cooper S, Bard J, English D, Arny M, Thomas L, Boyse EA (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci U S A 86:3828–3832PubMedPubMedCentralCrossRefGoogle Scholar
  21. Bustos ML, Huleihel L, Kapetanaki MG, Lino-Cardenas CL, Mroz L, Ellis BM, McVerry BJ, Richards TJ, Kaminski N, Cerdenes N, Mora AL, Rojas M (2014) Aging mesenchymal stem cells fail to protect because of impaired migration and antiinflammatory response. Am J Respir Crit Care Med 189(7):787–798PubMedPubMedCentralCrossRefGoogle Scholar
  22. Can A, Karahuseyinoglu S (2007) Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 25:2886–2895PubMedCrossRefGoogle Scholar
  23. Carlin R, Davis D, Weiss M, Schultz B, Troyer D (2006) Expression of early transcription factors Oct-4, Sox-2 and nanog by porcine umbilical cord (PUC) matrix cells. Reprod Biol Endocrinol 4:8PubMedPubMedCentralCrossRefGoogle Scholar
  24. Castro-Malaspina H, Gay RE, Resnick G, Kapoor N, Meyers P, Chiarieri D, McKenzie S, Broxmeyer HE, Moore MA (1980) Characterization of human bone marrow fibroblast colony-forming cells (CFU-F) and their progeny. Blood 56:289–301PubMedGoogle Scholar
  25. Che N, Li X, Zhou S, Liu R, Shi D, Lu L, Sun L (2012) Umbilical cord mesenchymal stem cells suppress B-cell proliferation and differentiation. Cell Immunol 274:46–53PubMedCrossRefGoogle Scholar
  26. Chen G, Yue A, Ruan Z, Yin Y, Wang R, Ren Y, Zhu L (2014) Human umbilical cord-derived mesenchymal stem cells do not undergo malignant transformation during long-term culturing in serum-free medium. PLoS One 9(6):e98565. doi: 10.1371/journal.pone.0098565 PubMedPubMedCentralCrossRefGoogle Scholar
  27. Chen Y-X, Zeng Z-C, Sun J, Zeng H-Y, Zhang Z-Y (2015) Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells. J Radiat Res 56(4):700–708PubMedPubMedCentralCrossRefGoogle Scholar
  28. Cheng H, Liu X, Hua R, Dai G, Wang X, Gao J, An Y (2014) Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med 12(1):1–8CrossRefGoogle Scholar
  29. Cho PS, Messina DJ, Hirsh EL, Chi N, Goldman SN, Lo DP, Harris IR, Popma SH, Sachs DH, Huang CA (2008) Immunogenicity of umbilical cord tissue derived cells. Blood 111:430–438PubMedCrossRefGoogle Scholar
  30. Conconi MT, Di Liddo R, Tommasini M, Calore C, Parnigotto PP (2011) Phenotype and differentiation potential of stromal populations obtained from various zones of human umbilical cord: an overview. Open Tissue Eng Regen Med J 4:6–20CrossRefGoogle Scholar
  31. Covas DT, Siufi JL, Silva AR, Orellana MD (2003) Isolation and culture of umbilical vein mesenchymal stem cells. Braz J Med Biol Res 36(9):1179–1183PubMedCrossRefGoogle Scholar
  32. Dalous J, Larghero J, Baud O (2012) Transplantation of umbilical cord-derived mesenchymal stem cells as a novel strategy to protect the central nervous system: technical aspects, preclinical studies, and clinical perspectives. Pediatr Res 71(4-2):482–490PubMedCrossRefGoogle Scholar
  33. Ding DC, Chang YH, Shyu WC, Lin SZ (2015) Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant 24(3):339–347. doi: 10.3727/096368915X686841 PubMedCrossRefGoogle Scholar
  34. Divya MS, Roshin GE, Divya TS, Rasheed VA, Santhoshkumar TR, Elizabeth KE, James J, Pillai RM (2012) Umbilical cord blood-derived mesenchymal stem cells consist of a unique population of progenitors co-expressing mesenchymal stem cell and neuronal markers capable of instantaneous neuronal differentiation. Stem Cell Res Ther 3(6):57PubMedPubMedCentralCrossRefGoogle Scholar
  35. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317PubMedCrossRefGoogle Scholar
  36. Ebrahimi-Barough S, Kouchesfahani HM, Ai J, Massumi M (2013) Differentiation of human endometrial stromal cells into oligodendrocyte progenitor cells (OPCs). J Mol Neurosci 51:265–273PubMedCrossRefGoogle Scholar
  37. Ebrahimi-Barough S, Javidan AN, Saberi H, Joghataei MT, Rahbarghazi R, Mirzaei E, Faghihi F, Shirian S, Ai A, Ai J (2015) Evaluation of motor neuron-like cell differentiation of hEnSCs on biodegradable PLGA nanofiber scaffolds. Mol Neurobiol 52(3):1704–1713PubMedCrossRefGoogle Scholar
  38. Ebrahimi-Barough S, Hoveizi E, Norouzi JA, Jafar Ai J (2015) Investigating the neuroglial differentiation effect of neuroblastoma conditioned medium in human endometrial stem cells cultured on 3D nanofibrous scaffold. J Biomed Mater Res A 103(8):2621–2627PubMedCrossRefGoogle Scholar
  39. Erices AA, Allers CI, Conget PA, Rojas CV, Minguell JJ (2003) Human cord blood-derived mesenchymal stem cells home and survive in the marrow of immunodeficient mice after systemic infusion. Cell Transplant 12(6):555–561PubMedCrossRefGoogle Scholar
  40. Farias VA, Linares-Fernández JL, Peñalver JL, Payá Colmenero JA, Ferrón GO, Duran EL, Fernández RM, Olivares EG, O’Valle F, Puertas A, Oliver FJ, Ruiz de Almodóvar JM (2011) Human umbilical cord stromal stem cell express CD10 and exert contractile properties. Placenta 32(1):86–95PubMedCrossRefGoogle Scholar
  41. Faroni A, Mobasseri SA, Kingham PJ, Reid AJ (2015) Peripheral nerve regeneration: experimental strategies and future perspectives. Adv Drug Deliv Rev 82:160–167PubMedCrossRefGoogle Scholar
  42. Fong CY, Richards M, Manasi N, Biswas A, Bongso A (2007) Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly. Rep Biomed Online 15(6):708–718CrossRefGoogle Scholar
  43. Fong CY, Chak LL, Biswas A, Tan JH, Gauthaman K, Chan WK, Bongso A (2011) Human Wharton’s jelly stem cells have unique transcriptome profiles compared to human embryonic stem cells and other mesenchymal stem cells. Stem Cell Rev 7(1):1–16PubMedCrossRefGoogle Scholar
  44. Fransson M, Piras E, Wang H, Burman J, Duprez I, Harris RA, LeBlanc K, Magnusson PU, Brittebo E, Loskog AS (2014) Intranasal delivery of central nervous system‐retargeted human mesenchymal stromal cells prolongs treatment efficacy of experimental autoimmune encephalomyelitis. Immunology 142(3):431–441PubMedPubMedCentralCrossRefGoogle Scholar
  45. Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16(3):381–390PubMedGoogle Scholar
  46. Friedman R, Betancur M, Boissel L, Tuncer H, Cetrulo C, Klingemann H (2007) Umbilical cord mesenchymal stem cells: adjuvants for human cell transplantation. Biol Blood Marrow Transplant 13(12):1477–1486PubMedCrossRefGoogle Scholar
  47. Fritsch MK, Singer DB (2008) Embryonic stem cell biology. Adv Pediatr 55:43–77PubMedCrossRefGoogle Scholar
  48. Fuks A, Banjo C, Shuster J, Freedman SO, Gold P (1975) Carcinoembryonic antigen (CEA): molecular biology and clinical significance. Biochim Biophys Acta 417(2):123–152PubMedGoogle Scholar
  49. Gärtner A, Pereira T, Armada-da-Silva P, Amado S, Veloso A, Amorim I, Ribeiro J, Santos J, Bárcia R, Cruz P (2014) Effects of umbilical cord tissue mesenchymal stem cells (UCX®) on rat sciatic nerve regeneration after neurotmesis injuries. J Stem Cells Regen Med 10(1):14PubMedPubMedCentralGoogle Scholar
  50. Geranmayeh MH, Baghbanzadeh A, Barin A, Salar-Amoli J, Dehghan MM, Rahbarghazi R, Azari H (2015) Paracrine neuroprotective effects of neural stem cells on glutamate-induced cortical neuronal cell excitotoxicity. Adv Pharm Bull 5(4):515–521PubMedPubMedCentralCrossRefGoogle Scholar
  51. Gluckman E, Broxmeyer HA, Auerbach AD, Friedman HS, Douglas GW, Devergie A (1989) Hematopoietic reconstitution in a patient with Fanconi’s anemia by means of umbilical cord blood from a HLA matched sibling. N Engl J Med 321:1174–1178PubMedCrossRefGoogle Scholar
  52. Gonzalez R, Griparic L, Umana M, Burgee K, Vargas V, Nasrallah R, Silva F, Patel A (2010) An efficient approach to isolation and characterization of pre- and postnatal umbilical cord lining stem cells for clinical applications. Cell Transplant 19(11):1439–1449PubMedCrossRefGoogle Scholar
  53. Gonzalez-Sanchez MB, Lopez-Valeiras E, Morente MM, Fernández Lago O (2013) Cost model for biobanks. Biopreserv Biobanking 11(5):272–277CrossRefGoogle Scholar
  54. Gotherstrom C, Ringden O, Westgren M, Tammik C, Le Blanc K (2003) Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant 32(3):265–272PubMedCrossRefGoogle Scholar
  55. Greider CW (1998) Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci U S A 95(1):90–92PubMedPubMedCentralCrossRefGoogle Scholar
  56. Guan J, Zhu Z, Zhao RC, Xiao Z, Wu C, Han Q, Chen L, Tong W, Zhang J, Han Q (2013) Transplantation of human mesenchymal stem cells loaded on collagen scaffolds for the treatment of traumatic brain injury in rats. Biomaterials 34(24):5937–5946PubMedCrossRefGoogle Scholar
  57. Guenther MG, Frampton GM, Soldner F, Hockemeyer D, Mitalipova M, Jaenisch R, Young RA (2010) Chromatin structure and gene expression programs of human embryonic and induced pluripotent stem cells. Cell Stem Cell 7(2):249–257PubMedPubMedCentralCrossRefGoogle Scholar
  58. Gupta PK, Das AK, Chullikana A, Majumdar AS (2012) Mesenchymal stem cells for cartilage repair in osteoarthritis. Stem Cell Res Ther 3(4):25PubMedPubMedCentralCrossRefGoogle Scholar
  59. Ha C-W, Park Y-B, Chung J-Y, Park Y-G (2015) Cartilage repair using composites of human umbilical cord blood-derived mesenchymal stem cells and hyaluronic acid hydrogel in a minipig model. Stem Cells Transl Med 4(9):1044–1051. doi: 10.5966/sctm.2014-0264 PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hamad A, Majda KY, Mohamed AF, Kazem B, Ashraf AM (2015) Multi-lineage differentiation of human umbilical cord Wharton’s jelly mesenchymal stromal cells mediates changes in the expression profile of stemness markers. PLoS One 10(4):e0122465CrossRefGoogle Scholar
  61. Han I, Yun M, Kim E-O, Kim B, Jung M-H, Kim S-H (2014) Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling. Stem Cell Res Ther 5(2):54PubMedPubMedCentralCrossRefGoogle Scholar
  62. Henningson CT Jr, Stanislaus MA, Gewirtz AM (2003) Embryonic and adult stem cell therapy. J Allergy Clin Immunol 111(2):S745–S753PubMedCrossRefGoogle Scholar
  63. Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD (2011) Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain 134(Pt 6):1790–1807. doi: 10.1093/brain/awr063 PubMedPubMedCentralCrossRefGoogle Scholar
  64. Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, Dahlke MH (2010) The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapy. Int Immunopharmacol 10(12):1496–1500PubMedCrossRefGoogle Scholar
  65. Hoynowski SM, Fry MM, Gardner BM, Leming MT, Tucker JR, Black L, Sand T, Mitchell KE (2007) Charaterization and differentiation of equine umbilical cord derived matrix cells. Biochem Biophys Res Commun 362:347–353PubMedCrossRefGoogle Scholar
  66. Hsieh JY, Fu YS, Chang SJ, Tsuang YH, Wang HW (2010) Functional module analysis reveals differential osteogenic and stemness potentials in human mesenchymal stem cells from bone marrow and Wharton’s jelly of umbilical cord. Stem Cells Dev 19:1895–1910PubMedCrossRefGoogle Scholar
  67. Ishige I, Nagamura-Inoue T, Honda MJ, Harnprasopwat R, Kido M, Sugimoto M, Nakauchi H, Tojo A (2009) Comparison of mesenchymal stem cells derived from arterial, venous, and Wharton’s jelly explants of human umbilical cord. Int J Hematol 90(2):261–269PubMedCrossRefGoogle Scholar
  68. Jiang J, Au M, Lu K, Eshpeter A, Korbutt G, Fisk G, Majumdar AS (2007) Generation of insulin‐producing islet‐like clusters from human embryonic stem cells. Stem Cells 25(8):1940–1953PubMedCrossRefGoogle Scholar
  69. Jing W, Chen Y, Lu L, Hu X, Shao C, Zhang Y, Zhou X, Zhou Y, Wu L, Liu R, Fan K, Jin G (2014) Human umbilical cord blood-derived mesenchymal stem cells producing IL15 eradicate established pancreatic tumor in syngeneic mice. Mol Cancer Ther 13(8):2127–2137. doi: 10.1158/1535-7163.mct-14-0175 PubMedCrossRefGoogle Scholar
  70. Jo CH, Kim OS, Park EY, Kim BJ, Lee JH, Kang SB, Lee JH, Han HS, Rhee SH, Yoon KS (2008) Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion. Cell Tissue Res 334(3):423–433PubMedCrossRefGoogle Scholar
  71. Kadam SS, Tiwari S, Bhonde RR (2009) Simultaneous isolation of vascular endothelial cells and mesenchymal stem cells from the human umbilical cord. In Vitro Cell Dev Biol Anim 45(1-2):23–27PubMedCrossRefGoogle Scholar
  72. Kalaszczynska I, Ferdyn K (2015) Wharton’s jelly derived mesenchymal stem cells: future of regenerative medicine? Recent findings and clinical significance. Biomed Res Int 2015:430847PubMedPubMedCentralCrossRefGoogle Scholar
  73. Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A (2007) Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells 25:319–331PubMedCrossRefGoogle Scholar
  74. Kim DW, Staples M, Shinozuka K, Pantcheva P, Kang S, Borlongan CV (2013) Wharton’s jelly-derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications. Int J Mol Sci 14:11692–11712PubMedPubMedCentralCrossRefGoogle Scholar
  75. Kim HJ, Seo SW, Chang JW, Lee JI, Kim CH, Chin J, Choi SJ, Kwon H, Yun HJ, Lee JM (2015) Stereotactic brain injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer’s disease dementia: a phase 1 clinical trial. Alzheimer’s Dement Transl Res Clin Interv 1(2):95–102CrossRefGoogle Scholar
  76. Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG (2010) Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells Dev 19(4):491–502PubMedCrossRefGoogle Scholar
  77. Koh SH, Kim KS, Choi MR, Jung KH, Park KS, Chai YG, Roh W, Hwang SJ, Ko HJ, Huh YM, Kim HT, Kim SH (2008) Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats. Brain Res 1229:233–248PubMedCrossRefGoogle Scholar
  78. La RG, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasà L, Cappello F, Zummo G, Farina F (2009) Isolation and characterization of Oct-4+/HLA-G+ mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochem Cell Biol 131(2):267–282CrossRefGoogle Scholar
  79. Le BK (2003) Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 5(6):485–489CrossRefGoogle Scholar
  80. Le Blanc K, Rasmusson I, Sundberg B, Götherström C, Hassan M, Uzunel M, Ringdén O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. The Lancet 363(9419):1439–1441CrossRefGoogle Scholar
  81. Lee OK, Kuo TK, Chen W-M, Lee K-D, Hsieh S-L, Chen T-H (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103(5):1669–1675PubMedCrossRefGoogle Scholar
  82. Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY (2010) A long‐term follow‐up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells 28(6):1099–1106PubMedCrossRefGoogle Scholar
  83. Li T, Yan Y, Wang B, Qian H, Zhang X, Shen L, Wang M, Zhou Y, Zhu W, Li W (2012) Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis. Stem Cells Dev 22(6):845–854PubMedPubMedCentralCrossRefGoogle Scholar
  84. Li X-Y, Zheng Z-H, Li X-Y, Guo J, Zhang Y, Li H, Wang Y-W, Ren J, Wu Z-B (2013) Treatment of foot disease in patients with type 2 diabetes mellitus using human umbilical cord blood mesenchymal stem cells: response and correction of immunological anomalies. Curr Pharm Des 19(27):4893–4899PubMedCrossRefGoogle Scholar
  85. Liang L, Yingfei G, Hongxia Z, Yaxin Y, Jinjin Z, Haiwei C, Lei W, Na L, Runmei L, Yunfeng X (2014) Aging increases the susceptivity of MSCs to reactive oxygen species and impairs their therapeutic potency for myocardial infarction. PLoS One 9(11):111850CrossRefGoogle Scholar
  86. Lim SY, Kim YS, Ahn Y, Jeong MH, Hong MH, Joo SY, Nam KI, Cho JG, Kang PM, Park JC (2006) The effects of mesenchymal stem cells transduced with Akt in a porcine myocardial infarction model. Cardiovasc Res 70(3):530–542. doi: 10.1016/j.cardiores.2006.02.016 PubMedCrossRefGoogle Scholar
  87. Lin Y-C, Ko T-L, Shih Y-H, Lin M-YA, Fu T-W, Hsiao H-S, Hsu J-YC, Fu Y-S (2011) Human umbilical mesenchymal stem cells promote recovery after ischemic stroke. Stroke 42(7):2045–2053PubMedCrossRefGoogle Scholar
  88. Liu J, Han D, Wang Z, Xue M, Zhu L, Yan H, Zheng X, Guo Z, Wang H (2013) Clinical analysis of the treatment of spinal cord injury with umbilical cord mesenchymal stem cells. Cytotherapy 15(2):185–191PubMedCrossRefGoogle Scholar
  89. Lu Z, Zhao H, Xu J, Zhang Z, Zhang X (2013) Human umbilical cord mesenchymal stem cells in the treatment of secondary progressive multiple sclerosis. J Stem Cell Res Ther 6:2Google Scholar
  90. Ma F, Chen D, Chen F, Chi Y, Han Z, Feng X, Li X (2015) Human umbilical cord mesenchymal stem cells promote breast cancer metastasis by interleukin-8 and interleukin-6 dependent induction of CD44 (+)/CD24 (-) cells. Cell Transplant 24(12):2585–2599PubMedCrossRefGoogle Scholar
  91. Maitra B, Szekely E, Gjini K, Laughlin MJ, Dennis J, Haynesworth SE, Koc ON (2004) Human mesenchymal stem cells support unrelated donor hematopoietic stem cells and suppress T-cell activation. Bone Marrow Transplant 33(6):597–604PubMedCrossRefGoogle Scholar
  92. Majore I, Moretti P, Stahl F, Hass R, Kasper C (2011) Growth and differentiation properties of mesenchymal stromal cell populations derived from whole human umbilical cord. Stem Cell Rev 7(1):17–31PubMedCrossRefGoogle Scholar
  93. Marcus AJ, Woodbury D (2008) Fetal stem cells from extra-embryonic tissues: do not discard. J Cell Mol Med 12(3):730–742PubMedPubMedCentralCrossRefGoogle Scholar
  94. Martin-Rendon E, Sweeney D, Lu F, Girdlestone J, Navarrete C, Watt SM (2008a) 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang 95(2):137–148PubMedCrossRefGoogle Scholar
  95. Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM (2008b) Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J 29(15):1807–1818PubMedCrossRefGoogle Scholar
  96. Mehrabi M, Mansouri K, Hosseinkhani S, Yarani R, Yari K, Bakhtiari M, Mostafaie A (2015) Differentiation of human skin-derived precursor cells into functional islet-like insulin-producing cell clusters. In Vitro Cell Dev Biol Anim 51:1–9CrossRefGoogle Scholar
  97. Mobarakeh ZT, Ai J, Yazdani F, Sorkhabadi SMR, Ghanbari Z, Javidan AN, Mortazavi‐Tabatabaei SAR, Massumi M, Barough SE (2012) Human endometrial stem cells as a new source for programming to neural cells. Cell Biol Int Rep 19(1):7–14CrossRefGoogle Scholar
  98. Mohammadi E, Nassiri SM, Rahbarghazi R, Siavashi V, Araghi A (2015) Endothelial juxtaposition of distinct adult stem cells activates angiogenesis signaling molecules in endothelial cells. Cell Tissue Res 362:1–13CrossRefGoogle Scholar
  99. Murry CE, Field LJ, Menasché P (2005) Cell-based cardiac repair: reflections at the 10-year point. Circulation 112(20):3174–3183. doi: 10.1161/circulationaha.105.546218 PubMedCrossRefGoogle Scholar
  100. Nekanti U, Rao VB, Bahirvani AG, Jan M, Totey S, Ta M (2010a) Longterm expansion and pluripotent marker array analysis of Wharton’s jelly-derived mesenchymal stem cells. Stem Cells Dev 19:117–130PubMedCrossRefGoogle Scholar
  101. Nekanti U, Mohanty L, Venugopal P, Balasubramanian S, Totey S, Ta M (2010b) Optimization and scale-up of Wharton’s jelly derived mesenchymal stem cells for clinical applications. Stem Cell Res 5(3):244–254PubMedCrossRefGoogle Scholar
  102. Newman AM, Cooper JB (2010) Lab-specific gene expression signatures in pluripotent stem cells. Cell Stem Cell 7(2):258–262PubMedCrossRefGoogle Scholar
  103. Niknamasl A, Ostad SN, Soleimani M, Azami M, Salmani MK, Lotfibakhshaiesh N, Ebrahimi-Barough S, Karimi R, Roozafzoon R, Ai J (2014) A new approach for pancreatic tissue engineering: human endometrial stem cells encapsulated in fibrin gel can differentiate to pancreatic islet beta-cell. Cell Biol Int 38(10):1174–1182PubMedCrossRefGoogle Scholar
  104. Okita K, Nagata N, Yamanaka S (2011) Immunogenicity of induced pluripotent stem cells. Circ Res 109(7):720–721. doi: 10.1161/RES.0b013e318232e187 PubMedCrossRefGoogle Scholar
  105. Panepucci RA, Siufi JL, Silva WA Jr, Proto-Siquiera R, Neder L, Orellana M, Rocha V, Covas DT, Zago MA (2004) Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 22(7):1263–1278PubMedCrossRefGoogle Scholar
  106. Pappa KI, Anagnou NP (2009) Novel sources of fetal stem cells: where do they fit on the developmental continuum? Regen Med 4:423–433PubMedCrossRefGoogle Scholar
  107. Perdikogianni C, Dimitriou H, Stiakaki E, Martimianaki G, Kalmanti M (2008) Could cord blood be a source of mesenchymal stromal cells for clinical use? Cytotherapy 10(5):452–459PubMedCrossRefGoogle Scholar
  108. Phadnis SM, Ghaskadbi SM, Hardikar AA, Bhonde RR (2009) Mesenchymal stem cells derived from bone marrow of diabetic patients portrait unique markers influenced by the diabetic microenvironment. Rev Diabet Stud 6(4):260–270PubMedCrossRefGoogle Scholar
  109. Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11(10):1255–1265PubMedCrossRefGoogle Scholar
  110. Pijnappels DA, Schalij MJ, Ramkisoensing AA, van Tuyn J, de Vries AAF, van der Laarse A, Ypey DL, Atsma DE (2008) Forced alignment of mesenchymal stem cells undergoing cardiomyogenic differentiation affects functional integration with cardiomyocyte cultures. Circ Res 103(2):167–176. doi: 10.1161/circresaha.108.176131 PubMedCrossRefGoogle Scholar
  111. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  112. Pountos I, Giannoudis PV, Jones E, English A, Churchman S, Field S, Ponchel F, Bird H, Emery P, McGonagle D (2011) NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man. J Cell Mol Med 15(3):525–534PubMedCrossRefGoogle Scholar
  113. Prasanna SJ, Jahnavi VS (2011) Wharton’s jelly mesenchymal stem cells as off-the-shelf cellular therapeutics: a closer look into their regenerative and immunomodulatory properties. Open Tissue Eng Regen Med J 4:28–38CrossRefGoogle Scholar
  114. Rachakatla RS, Marini F, Weiss ML, Tamura M, Troyer D (2007) Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther 14(10):828–835PubMedCrossRefGoogle Scholar
  115. Rahbarghazi R, Nassiri SM, Khazraiinia P, Kajbafzadeh A-M, Ahmadi SH, Mohammadi E, Molazem M, Zamani-Ahmadmahmudi M (2012) Juxtacrine and paracrine interactions of rat marrow-derived mesenchymal stem cells, muscle-derived satellite cells, and neonatal cardiomyocytes with endothelial cells in angiogenesis dynamics. Stem Cells Dev 22(6):855–865PubMedPubMedCentralCrossRefGoogle Scholar
  116. Rahbarghazi R, Nassiri SM, Ahmadi SH, Mohammadi E, Rabbani S, Araghi A, Hosseinkhani H (2014) Dynamic induction of pro-angiogenic milieu after transplantation of marrow-derived mesenchymal stem cells in experimental myocardial infarction. Int J Cardiol 173(3):453–466PubMedCrossRefGoogle Scholar
  117. Rahman MJ, Regn D, Bashratyan R, Dai YD (2014) Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice. Diabetes 63(3):1008–1020PubMedPubMedCentralCrossRefGoogle Scholar
  118. Ratanatharathorn V, Ayash L, Lazarus H, Fu J, Uberti J (2001) Chronic graft-versus-host disease: clinical manifestation and therapy. Bone Marrow Transplant 28(2):121–129PubMedCrossRefGoogle Scholar
  119. Rennert RC, Sorkin M, Januszyk M, Duscher D, Kosaraju R, Chung MT, Lennon J, Radiya-Dixit A, Raghvendra S, Maan ZN, Hu MS, Rajadas J, Rodrigues M, Gurtner GC (2014) Diabetes impairs the angiogenic potential of adipose-derived stem cells by selectively depleting cellular subpopulations. Stem Cell Res Ther 5(3):79PubMedPubMedCentralCrossRefGoogle Scholar
  120. Reza HM, Ng BY, Phan TT, Tan DT, Beuerman RW, Ang LP (2011) Characterization of a novel umbilical cord lining cell with CD227 positivity and unique pattern of P63 expression and function. Stem Cell Rev 7(3):624–638PubMedCrossRefGoogle Scholar
  121. Ringdén O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lönnies H, Marschall H-U, Dlugosz A, Szakos A, Hassan Z (2006) Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81(10):1390–1397PubMedCrossRefGoogle Scholar
  122. Riteau B, Moreau P, Menier C, Khalil-Daher I, Khosrotehrani K, Bras-Goncalves R, Paul P, Dausset J, Rouas-Freiss N, Carosella ED (2001) Characterization of HLA-G1, -G2, -G3, and -G4 isoforms transfected in a human melanoma cell line. Transplant Proc 33:2360–2364PubMedCrossRefGoogle Scholar
  123. Roobrouck VD, Ulloa-Montoya F, Verfaillie CM (2008) Self-renewal and differentiation capacity of young and aged stem cells. Exp Cell Res 314(9):1937–1944PubMedCrossRefGoogle Scholar
  124. Rosa T, BacklyRania E (2015) Transplanted umbilical cord mesenchymal stem cells modify the in vivo microenvironment enhancing angiogenesis and leading to bone regeneration. Stem Cells Dev 24(13):1570–1581CrossRefGoogle Scholar
  125. Roura S, Bagó JR, Soler-Botija C, Pujal JM, Gálvez-Montón C, Prat-Vidal C, Llucià-Valldeperas A, Blanco J, Bayes-Genis A (2012) Human umbilical cord blood-derived mesenchymal stem cells promote vascular growth in vivo. PLoS One 7(11):e49447PubMedPubMedCentralCrossRefGoogle Scholar
  126. Salehinejad P, Alitheen NB, Ali AM, Omar AR, Mohit M, Janzamin E, Samani FS, Torshizi Z, Nematollahi-Mahani SN (2012) Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton’s jelly. In Vitro Cell Dev Biol Anim 48(2):75–83PubMedCrossRefGoogle Scholar
  127. Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE (2005) Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 23(2):220–229PubMedCrossRefGoogle Scholar
  128. Sarugaser R, Hanoun L, Keating A, Stanford WL, Davies JE (2009) Human mesenchymal stem cells self-renew and differentiate according to a deterministic hierarchy. PLoS One 4(8):e6498PubMedPubMedCentralCrossRefGoogle Scholar
  129. Sarvandi SS, Joghataei MT, Parivar K, Khosravi M, Sarveazad A, Sanadgol N (2015) In vitro differentiation of rat mesenchymal stem cells to hepatocyte lineage. Iran J Basic Med Sci 18(1):89PubMedPubMedCentralGoogle Scholar
  130. Secco M, Moreira YB, Zucconi E, Vieira NM, Jazedje T, Muotri AR, Okamoto OK, Verjovski-Almeida S, Zatz M (2009) Gene expression profile of mesenchymal stem cells from paired umbilical cord units: cord is different from blood. Stem Cell Rev 5(4):387–401PubMedPubMedCentralCrossRefGoogle Scholar
  131. Seshareddy K, Troyer D, Weiss ML (2008) Method to isolate mesenchymal-like cells from Wharton’s Jelly of umbilical cord. Methods Cell Biol 86:101–119PubMedCrossRefGoogle Scholar
  132. Shapiro AJ, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV (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
  133. Shawki S, Gaafar T, Erfan H, Khateeb EE, Sheikhah AE, Hawary RE (2015) Immunomodulatory effect of umbilical cord derived mesenchymal stem cells. Microbiol Immunol 59(6):348–356PubMedCrossRefGoogle Scholar
  134. Si Y, Zhao Y, Hao H, Liu J, Guo Y, Mu Y, Shen J, Cheng Y, Fu X, Han W (2012) Infusion of mesenchymal stem cells ameliorates hyperglycemia in type 2 diabetic rats: identification of a novel role in improving insulin sensitivity. Diabetes 61(6):1616–1625. doi: 10.2337/db11-1141 PubMedPubMedCentralCrossRefGoogle Scholar
  135. Stefano F, Serena V, Lucia VF, Miriana JQ, Giampiero L, Alberto T, Erica V (2015) Wharton’s jelly derived mesenchymal stromal cells: biological properties, induction of neuronal phenotype and current applications in neurodegeneration research. Acta Histochem 117(4-5):329–338CrossRefGoogle Scholar
  136. Stolzing A, Jones E, McGonagle D, Scutt A (2008) Age-related changes in human bone marrow-derived mesenchymal stem cells: consequences for cell therapies. Mech Ageing Dev 129(3):163–173PubMedCrossRefGoogle Scholar
  137. Subramanian A, Fong CY, Biswas A, Bongso A (2015) Comparative characterization of cells from the various compartments of the human umbilical cord shows that the Wharton’s jelly compartment provides the best source of clinically utilizable mesenchymal stem cells. PLoS One 10(6):e0127992PubMedPubMedCentralCrossRefGoogle Scholar
  138. Sun L, Wang D, Liang J, Zhang H, Feng X, Wang H, Hua B, Liu B, Ye S, Hu X (2010) Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62(8):2467–2475PubMedCrossRefGoogle Scholar
  139. Sung M-A, Jung HJ, Lee J-W, Lee J-Y, Pang K-M, Yoo SB, Alrashdan MS, Kim S-M, Jahng JW, Lee J-H (2012) Human umbilical cord blood-derived mesenchymal stem cells promote regeneration of crush-injured rat sciatic nerves. Neural Regen Res 7(26):2018PubMedPubMedCentralGoogle Scholar
  140. Taghizadeh RR, Cetrulo KJ, Cetrulo CL (2011) Wharton’s jelly stem cells: future clinical applications. Placenta 32(4):311–315CrossRefGoogle Scholar
  141. Tehrani HJ, Parivar K, Ai J, Kajbafzadeh A, Rahbarghazi R, Hashemi M, Sadeghizadeh M (2014) Effect of dexamethasone, insulin and EGF on the myogenic potential on human endometrial stem cell. Iran J Pharm Res 13(2):659Google Scholar
  142. Thomson JA, Itskovitz-Eldor J, Shapiro SS (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  143. Tolar J, Le Blanc K, Keating A, Blazar BR (2010) Concise review: hitting the right spot with mesenchymal stromal cells. Stem Cells 28(8):1446–1455PubMedPubMedCentralCrossRefGoogle Scholar
  144. Toma C, Pittenger MF, Cahill KS, Byrne BJ, Kessler PD (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105(1):93–98. doi: 10.1161/hc0102.101442 PubMedCrossRefGoogle Scholar
  145. Tong CK, Vellasamy S, Tan BC, Abdullah M, Vidyadaran S, Seow HF, Ramasamy R (2011) Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method. Cell Biol Int 35(3):221–226PubMedCrossRefGoogle Scholar
  146. Troyer DL, Weiss ML (2008) Concise review: Wharton’s jelly-derived cells are a primitive stromal cell population. Stem Cells 26:591–599PubMedCrossRefGoogle Scholar
  147. Tsagias N, Koliakos I, Karagiannis V, Eleftheriadou M, Koliakos GG (2011) Isolation of mesenchymal stem cells using the total length of umbilical cord for transplantation purposes. Transfus Med 21(4):253–261PubMedCrossRefGoogle Scholar
  148. Tsai PC, Fu TW, Chen YMA, Ko TL, Chen TH, Shih YH, Hung SC, Fu YS (2009) The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis. Liver Transpl 15(5):484–495PubMedCrossRefGoogle Scholar
  149. Vogelaar CF, Vrinten DH, Hoekman MF, Brakkee JH, Burbach JPH, Hamers FP (2004) Sciatic nerve regeneration in mice and rats: recovery of sensory innervation is followed by a slowly retreating neuropathic pain-like syndrome. Brain Res 1027(1):67–72PubMedCrossRefGoogle Scholar
  150. Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337PubMedCrossRefGoogle Scholar
  151. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J (2009) The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 126(2):220–232PubMedPubMedCentralCrossRefGoogle Scholar
  152. Wang S, Qu X, Zhao RC (2012) Clinical applications of mesenchymal stem cells. J Hematol Oncol 5(1):19PubMedPubMedCentralCrossRefGoogle Scholar
  153. Wang Y, Zhang Z, Chi Y, Zhang Q, Xu F, Yang Z, Meng L, Yang S, Yan S, Mao A, Zhang J, Yang Y, Wang S, Cui J, Liang L, Ji Y, Han ZB, Fang X, Han ZC (2013) Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation. Cell Death Dis 4:e950. doi: 10.1038/cddis.2013.480 PubMedPubMedCentralCrossRefGoogle Scholar
  154. Weiss ML, Troyer DL (2006) Stem cells in the umbilical cord. Stem Cell Rev 2(2):155–162PubMedPubMedCentralCrossRefGoogle Scholar
  155. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D (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
  156. Weiss M, Anderson C, Medicetty S, SeshareddyK B, Weiss RJ, Vanderwerff I, Troyer D, Mcintosh KR (2008) Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells 26:2865–2874PubMedCrossRefGoogle Scholar
  157. Weissman IL, Anderson DJ, Gage F (2001) Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol 17:387–403PubMedCrossRefGoogle Scholar
  158. Welte K, Foeken L, Gluckman E, Navarrete C, Cord Blood Working Group of the World Marrow Donor Association (2010) International exchange of cord blood units: the registry aspects. Bone Marrow Transplant 45:825–831PubMedCrossRefGoogle Scholar
  159. Wetzig A, Alaiya A, Al-Alwan M, Pradez CB, Pulicat MS, Al-Mazrou A, Shinwari Z, Sleiman GM, Ghebeh H, Al-Humaidan H, Gaafar A, Kanaan I, Adra C (2013) Differential marker expression by cultures rich in mesenchymal stem cells. BMC Cell Biol 14:54PubMedPubMedCentralCrossRefGoogle Scholar
  160. Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM (2003) Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol 121(2):368–374PubMedCrossRefGoogle Scholar
  161. Wu X-B, Tao R (2012) Hepatocyte differentiation of mesenchymal stem cells. Hepatobiliary Pancreat Dis Int 11(4):360–371PubMedCrossRefGoogle Scholar
  162. Xu Z, Sheng L, Ouyang G (2014) [Umbilical cord blood-derived mesenchymal stem cells inhibit proliferation of peripheral blood lymphocytes]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30(9):968–971PubMedGoogle Scholar
  163. Yamashita A, Liu S, Woltjen K, Thomas B, Meng G, Hotta A, Takahashi K, Ellis J, Yamanaka S, Rancourt DE (2013) Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells. Sci Rep 3:1978PubMedPubMedCentralGoogle Scholar
  164. Yan Y, Xu W, Qian H, Si Y, Zhu W, Cao H, Zhou H, Mao F (2009) Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo. Liver Int 29(3):356–365PubMedCrossRefGoogle Scholar
  165. Yasuda K, Yashiro M, Sawada T, Ohira M, Hirakawa K (2007) ERas oncogene expression and epigenetic regulation by histone acetylation in human cancer cells. Anticancer Res 27(6B):4071–4075PubMedGoogle Scholar
  166. Yoon JH, Roh EY, Shin S, Jung NH, Song EY, Chang JY, Kim BJ, Jeon HW (2013) Comparison of explant-derived and enzymatic digestion-derived MSCs and the growth factors from Wharton’s jelly. Biomed Res Int 2013:428726PubMedPubMedCentralGoogle Scholar
  167. Yuan Y, Chen D, Chen X, Shao H, Huang S (2014) Human umbilical cord-derived mesenchymal stem cells inhibit proliferation but maintain survival of Jurkat leukemia cells in vitro by activating Notch signaling. Nan Fang Yi Ke Da Xue Xue Bao 34(4):441–447PubMedGoogle Scholar
  168. Zhang Z, Lin H, Shi M, Xu R, Fu J, Lv J, Chen L, Lv S, Li Y, Yu S (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 27(s2):112–120PubMedCrossRefGoogle Scholar
  169. Zhang L, Xiang J, Li G (2013) The uncertain role of unmodified mesenchymal stem cells in tumor progression: what master switch? Stem Cell Res Ther 4(2):22PubMedPubMedCentralCrossRefGoogle Scholar
  170. Zhao T, Zhang Z-N, Rong Z, Xu Y (2011) Immunogenicity of induced pluripotent stem cells. Nature 474(7350):212–215PubMedCrossRefGoogle Scholar
  171. Zhi-Gang Z, Wei-Ming L, Zhi-Chao C, Yong Y, Ping Z (2008) Immunosuppressive properties of mesenchymal stem cells derived from bone marrow of patient with hematological malignant diseases. Leuk Lymphoma 49(11):2187–2195PubMedCrossRefGoogle Scholar
  172. Zhou C, Yang B, Tian Y (2011) Immunomodulatory effect of human umbilical cord Wharton’s jelly-derived mesenchymal stem cells on lymphocytes. Cell Immunol 272(1):33–38PubMedPubMedCentralCrossRefGoogle Scholar
  173. Zhou R, Li Z, He C, Li R, Xia H, Li C, Xiao J, Chen Z-Y (2014) Human umbilical cord mesenchymal stem cells and derived hepatocyte-like cells exhibit similar therapeutic effects on an acute liver failure mouse model. PLoS One 9(8):e104392. doi: 10.1371/journal.pone.0104392 PubMedPubMedCentralCrossRefGoogle Scholar
  174. Hou Z-l, Liu Y, Mao X-H, Wei C-y, Meng M-y, Liu Y-h, Zhuyun Yang Z, Zhu H, Short M, Bernard C, Xiao Z-c (2013) Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis. Cell Adh Migr 7(5):404–407. doi: 10.4161/cam.26941 PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Somayeh Ebrahimi-Barough
    • 1
    Email author
  • Reza Rahbarghazi
    • 2
    • 3
  • Zohreh Bagher
    • 4
  • Jafar Ai
    • 1
  • Elham Hoveizi
    • 5
  1. 1.Department of Tissue Engineering and Applied Cell Sciences, Faculty of Advanced Technologies in MedicineTehran University of Medical SciencesTehranIran
  2. 2.Stem Cell Research Center, Tabriz University of Medical SciencesTabrizIran
  3. 3.Department of Applied Cell Sciences, Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran
  4. 4.ENT and Head & Neck Research Center and DepartmentHazrat Rasoul Akram Hospital, Iran University of Medical SciencesTehranIran
  5. 5.Department of Biology, Faculty of SciencesShahid Chamran University of AhvazAhvazIran

Personalised recommendations