Advertisement

Umbilical Cord Tissue and Wharton’s Jelly Mesenchymal Stem Cells Properties and Therapeutic Potentials

  • Erdal Karaöz
  • Çiğdem İnci
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

Umbilical cord (UC) tissue, which provides the fetus with nutrient-rich, oxygenated blood is one of the most promising sources of stem cells with several advantages. Mesenchymal stem cells (MSCs) isolate from different regions of UC such as Wharton’s jelly (WJ), amnion, perivascular area, arteries, and vein. WJ-derived MSCs have some advantages over other regions of UC. Larger numbers of MSCs could be harvested from WJ with a reduced amount of non-MSC contaminants and they retain their differentiation and proliferation abilities for long periods of time in culture conditions.

In this chapter, we give a brief review about, in vitro and preclinical studies and the potential therapeutic effects of WJ-MSCs for clinic applications through their homing, chemoattraction, survival, multilineage differentiation potential, immunomodulation, antiapoptotic, and anti-inflammatory abilities.

Keywords

Immunomodulation Mesenchymal stromal cells Umbilical Cord Wharton jelly 

Notes

Acknowledgements

The authors would like to thank AyberkAkat, M.Sc. for his contributions in the writing of the manuscript.

References

  1. Agah E, Parivar K, Joghataei M (2013) Therapeutic effect of transplanted human Wharton’s Jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis. Mol Neurobiol 49:625–632CrossRefGoogle Scholar
  2. Amorin B, Alegretti A, Valim V et al (2014) Mesenchymal stem cell therapy and acute graft-versus-host disease: a review. Hum Cell 27(4):137–150PubMedPubMedCentralCrossRefGoogle Scholar
  3. Antoninus A, Widowati W, Wijaya L et al (2015) Human platelet lysate enhances the proliferation of Wharton’s jelly-derived mesenchymal stem cells. Biomark Genom Med 7:87–97CrossRefGoogle Scholar
  4. Arufe M, Fuente A, Mateos J et al (2011) Analysis of the chondrogenic potential and secretome of mesenchymal stem cells derived from human umbilical cord stroma. Stem Cells Dev 20:1199–1212PubMedCrossRefGoogle Scholar
  5. Ayuzawa R, Doi C, Rachakatla R et al (2009) Naïve human umbilical cord matrix derived stem cells significantly attenuate growth of human breast cancer cells in vitro and in vivo. Cancer Lett 280:31–37PubMedPubMedCentralCrossRefGoogle Scholar
  6. Bailey M, Wang L, Bode C et al (2007) A comparison of human umbilical cord matrix stem cells and temporomandibular joint condylar chondrocytes for tissue engineering temporomandibular joint condylar cartilage. Tissue Eng 13:2003–2010PubMedCrossRefGoogle Scholar
  7. Baksh D, Yao R, Tuan R (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
  8. Balow J (2005) Clinical presentation and monitoring of lupus nephritis. Lupus 14:25–30PubMedCrossRefGoogle Scholar
  9. 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 40:143–151PubMedPubMedCentralGoogle Scholar
  10. Broxmeyer H, Douglas G, Hangoc G et al (1989) Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc Natl Acad Sci 86:3828–3832PubMedPubMedCentralCrossRefGoogle Scholar
  11. Bruno S, Grange C, Collino F et al (2012) Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury. PLoS One 7(3):e33115PubMedPubMedCentralCrossRefGoogle Scholar
  12. 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
  13. Carlin R, Davis D, Weiss M et al (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
  14. Chen H, Zhang Y, Yang Z et al (2013) Human umbilical cord Wharton’s jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration. Neural Regen Res 8(10):890–899PubMedPubMedCentralGoogle Scholar
  15. Conconi MT, Liddo LD, Tommasini M et al (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
  16. Corotchi M, Popa M, Remes A et al (2013) Isolation method and xeno-free culture conditions influence multipotent differentiation capacity of human Wharton’s jelly-derived mesenchymal stem cells. Stem Cell Res Amp Ther 4:81CrossRefGoogle Scholar
  17. Crewe N, Krause JS (2002) Spinal cord injuries. In: Brodwin MG, Tellez FA, Brodwin SK (eds) Medical, psychosocial, and vocational aspects of disability, 2nd edn. Athens, Elliott & Fitzpatrick, pp 279–291Google Scholar
  18. Dahlin R, Kinard L, Lam J et al (2014) Articular chondrocytes and mesenchymal stem cells seeded on biodegradable scaffolds for the repair of cartilage in a rat osteochondral defect model. Biomaterials 35:7460–7469PubMedPubMedCentralCrossRefGoogle Scholar
  19. Ding DC, Chou HL, Chang YH et al (2015) Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma derived stem cells. Cell Transplant 25:217–228PubMedCrossRefGoogle Scholar
  20. Doi C, Maurya DK, Pyle MM et al (2010) Cytotherapy with naive rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases survival in syngeneic mice. Cytotherapy 12(3):408–417PubMedPubMedCentralCrossRefGoogle Scholar
  21. Doitsidou M, Reichman-Fried M, Stebler J et al (2002) Guidance of primordial germ cell migration by the chemokine SDF-1. Cell 111:647–659PubMedCrossRefGoogle Scholar
  22. Dominici M, Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317PubMedCrossRefGoogle Scholar
  23. Dongmei H, Jing L, Mei X et al (2011) Clinical analysis of the treatment of spinocerebellar ataxia and multiple system atrophy-cerebellar type with umbilical cord mesenchymal stromal cells. Cytotherapy 13:913–917PubMedCrossRefGoogle Scholar
  24. Falah M, Nierenberg G, Soudry M et al (2010) Treatment of articular cartilage lesions of the knee. Int Orthop 34:621–630PubMedPubMedCentralCrossRefGoogle Scholar
  25. Fong C, Richards M, Manasi N et al (2007) Comparative growth behaviour and characterization of stem cells from human Wharton’s jelly. Reprod Biomed Online 15:708–718PubMedCrossRefGoogle Scholar
  26. Fong C-Y, Chak L-L, Biswas A et al (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 7:1–16PubMedCrossRefGoogle Scholar
  27. Gauthaman K, Yee F, Cheyyatraivendran S et al (2012) Human umbilical cord wharton’s jelly stem cell (hWJSC) extracts inhibit cancer cell growth in vitro. J Cell Biochem 113:2027–2039PubMedCrossRefGoogle Scholar
  28. Ghodke-Puranik Y, Niewold T (2015) Immunogenetics of systemic lupus erythematosus: a comprehensive review. J Autoimmun 64:125–136PubMedPubMedCentralCrossRefGoogle Scholar
  29. Gluckman E, Rocha V (2005) History of the clinical use of umbilical cord blood hematopoietic cells. Cytotherapy 7:219–227PubMedCrossRefGoogle Scholar
  30. Han Y, Chai J, Sun T et al (2011) Differentiation of human umbilical cord mesenchymal stem cells into dermal fibroblasts in vitro. Biochem Bioph Res Co 413:561–565CrossRefGoogle Scholar
  31. He H, Nagamura-Inoue T, Takahashi A et al (2015) Immunosuppressive properties of Wharton’s jelly-derived mesenchymal stromal cells in vitro. Int J Hematol 102(3):368–378PubMedCrossRefGoogle Scholar
  32. Hentze H, Soong P, Wang S et al (2009) Teratoma formation by human embryonic stem cells: evaluation of essential parameters for future safety studies. Stem Cell Res 2:198–210PubMedCrossRefGoogle Scholar
  33. Hoeben A, Landuyt B, Highley MS et al (2004) Vascular endothelial growth factor and angiogenesis. Pharmacol Rev 56(4):549–580PubMedCrossRefGoogle Scholar
  34. Hoerstrup SP, Kadner A, Breymann C et al (2002) Living, autologous pulmonary artery conduits tissue engineered from umbilical cord cells. Ann Thorac Surg 74(1):46–52PubMedCrossRefGoogle Scholar
  35. Hollweck T, Hartmann I, Eblenkamp M (2011) Cardiac differentiation of Human Wharton`s jelly stem cells—experimental comparison of protocols. Open Tissue Eng Regen Med J 4:95–102CrossRefGoogle Scholar
  36. Horuk R, Peiper S (1996) Chemokines: molecular double agents. Curr Biol 6:1581–1582PubMedCrossRefGoogle Scholar
  37. Hu J, Yu X, Wang Z et al (2013) 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 60(3):347–357PubMedCrossRefGoogle Scholar
  38. Jacobs SA, Roobrouck VD, Verfaillie CM et al (2013) Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells. Immunol Cell Biol 91(1):32–39PubMedPubMedCentralCrossRefGoogle Scholar
  39. Jieanu CF, Ungureanu BS, Săndulescu DL et al (2015) Quantification of liver fibrosis in chronic hepatitis B virus infection. J Med Life 8(3):285–290PubMedPubMedCentralGoogle Scholar
  40. Jin JL, Liu Z, Lu ZJ et al (2013) Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 10(1):11–20PubMedCrossRefGoogle Scholar
  41. Jonsdottir-Buch S, Lieder R, Sigurjonsson O (2013) Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells. PLoS One 8(7):e68984PubMedPubMedCentralCrossRefGoogle Scholar
  42. 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
  43. Kanehira M, Xin H, Hoshino K et al (2007) Targeted delivery of NK4 to multiple lung tumors by bone marrow-derived mesenchymal stem cells. Cancer Gene Ther 14:894–903PubMedCrossRefGoogle Scholar
  44. Kao SY, Shyu JF, Wang HS et al (2015) Comparisons of differentiation potential in human mesenchymal stem cells from Wharton’s jelly, bone marrow, and pancreatic tissues. Stem Cells Int 2015:306158PubMedPubMedCentralCrossRefGoogle Scholar
  45. Kaveh M, Mehdi A, Farid A et al (2013) Restoration of heart function using transplantation of human umbilical cord matrix-derived cardiomyocytes and vascular endothelial growth factor. Open Tissue Eng Regen Med J 6:26–36CrossRefGoogle Scholar
  46. Khakoo A, Pati S, Anderson S et al (2006) Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi’s sarcoma. J Exp Med 203:1235–1247PubMedPubMedCentralCrossRefGoogle Scholar
  47. Kholodenko IV, Konieva AA, Kholodenko RV et al (2013) Molecular mechanisms of migration and homing of intravenously transplanted mesenchymal stem cells. J Regen Med 2:4Google Scholar
  48. Killat J, Reimers K, Choi C et al (2013) Cultivation of keratinocytes and fibroblasts in a three-dimensional bovine collagen-elastin matrix (Matriderm®) and application for full thickness wound coverage in vivo. Int J Mol Sci 14(7):14460–14474PubMedPubMedCentralCrossRefGoogle Scholar
  49. Kim H-S, Choi D-Y, Yun S et al (2012) Proteomic analysis of microvesicles derived from human mesenchymal stem cells. J Proteome Res 11:839–849PubMedCrossRefGoogle Scholar
  50. Klyushnenkova E, Mosca J, Zernetkina V et al (2005) T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci 12:47–57PubMedCrossRefGoogle Scholar
  51. Knudtzon S (1974) In vitro growth of granulocytic colonies from circulating cells in human cord blood. Blood 43(3):357–361PubMedGoogle Scholar
  52. Kohanim S, Palioura S, Saeed HN (2016) Stevens-Johnson syndrome/toxic epidermal necrolysis - a comprehensive review and guide to therapy. I. Systemic Disease. Ocul Surf 14(1):2–19PubMedCrossRefGoogle Scholar
  53. Kurtzberg J, Prockop S, Teira P et al (2014) Allogeneic human mesenchymal stem cell therapy (Remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients. Biol Blood Marrow Transplant 20:229–235PubMedCrossRefGoogle Scholar
  54. Lai R, Chen T, Lim S (2011) Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med 6:481–492PubMedCrossRefGoogle Scholar
  55. Latifpour M, Nematollahi-Mahani SN, Deilamy M et al (2011) Improvement in cardiac function following transplantation of human umbilical cord matrix-derived mesenchymal cells. Cardiology 120:9–18PubMedGoogle Scholar
  56. Le Blanc K, Rasmusson I, Sundberg B et al (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419):1439–1441PubMedCrossRefGoogle Scholar
  57. Lee U, Friedman S (2011) Mechanisms of hepatic fibrogenesis. Best Pract Res Clin Gastroenterol 25:195–206PubMedPubMedCentralCrossRefGoogle Scholar
  58. Lee H, Lee J, Lee H et al (2010) The therapeutic potential of human umbilical cord blood-derived mesenchymal stem cells in Alzheimer’s disease. Neurosci Lett 481:30–35PubMedCrossRefGoogle Scholar
  59. Leite C, Silva NT, Mendes S et al (2014) Differentiation of human umbilical cord matrix mesenchymal stem cells into neural-like progenitor cells and maturation into an oligodendroglial-like lineage. PLoS One 9(10):e111059PubMedPubMedCentralCrossRefGoogle Scholar
  60. Leng X, Zhang Q, Zhai X, Chen Z (2012) Local transplant of human umbilical cord matrix stem cells improves skin flap survival in a mouse model. Tohoku J Exp Med 227:191–197PubMedCrossRefGoogle Scholar
  61. Li Z, He C, Xiao J, Chen Z (2013a) Treating end-stage liver diseases with mesenchymal stem cells: an oak is not felled at one stroke. Oa Tissue Eng 1(1):3CrossRefGoogle Scholar
  62. Li X, Wang D, Lu Z et al (2013b) Umbilical cord mesenchymal stem cell transplantation in drug-induced Stevens—Johnson syndrome. J Eur Acad Dermatol Venereol 27:659–661PubMedCrossRefGoogle Scholar
  63. Li T, Yan Y, Wang B et al (2013c) Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Alleviate Liver Fibrosis. Stem Cells Dev 22:845–854PubMedCrossRefGoogle Scholar
  64. Liang J, Gu F, Wang H et al (2010) Mesenchymal stem cell transplantation for diffuse alveolar hemorrhage in SLE. Nat Rev Rheumatol 6:486–489PubMedCrossRefGoogle Scholar
  65. Lila N, Carpentier A, Amrein C et al (2000) Implication of HLA-G molecule in heart-graft acceptance. Lancet Lond Engl 355:2138CrossRefGoogle Scholar
  66. Lin S-Z, Chang Y-J, Liu J-W et al (2010) Transplantation of human Wharton’s jelly-derived stem cells alleviates chemically induced liver fibrosis in rats. Cell Transplant 19:1451–1463PubMedCrossRefGoogle Scholar
  67. Liu S, Hou K, Yuan M et al (2014a) Characteristics of mesenchymal stem cells derived from Wharton’s jelly of human umbilical cord and for fabrication of non-scaffold tissue-engineered cartilage. J Biosci Bioeng 117:229–235PubMedCrossRefGoogle Scholar
  68. Liu X, Zheng P, Wang X et al (2014b) A preliminary evaluation of efficacy and safety of Wharton’s jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus. Stem Cell Res Ther 5:57PubMedPubMedCentralCrossRefGoogle Scholar
  69. Lv Y-T, Zhang Y, Liu M et al (2013) Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J Transl Med 11:196PubMedPubMedCentralCrossRefGoogle Scholar
  70. Magenau J, Reddy P (2014) Next generation treatment of acute graft-versus-host disease. Leukemia 28:2283–2291PubMedCrossRefGoogle Scholar
  71. Matsuzuka T, Rachakatla R, Doi C et al (2010) Human umbilical cord matrix-derived stem cells expressing interferon-β gene significantly attenuate bronchioloalveolar carcinoma xenografts in SCID mice. Lung Cancer 70:28–36PubMedPubMedCentralCrossRefGoogle Scholar
  72. McElreavey KD, Irvine AI, Ennis KT et al (1991) Isolation, culture and characterisation of fibroblast-like cells derived from the Wharton's jelly portion of human umbilical cord. Biochem Soc Trans 19(1):29SPubMedCrossRefGoogle Scholar
  73. Mennan C, Wright K, Bhattacharjee A et al (2013) Isolation and characterisation of mesenchymal stem cells from different regions of the human umbilical cord. Biomed Res Int 2013:916136PubMedPubMedCentralCrossRefGoogle Scholar
  74. Mohamadnejad M, Alimoghaddam K, Mohyeddin-Bonab M et al (2007) Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 10:459–466PubMedGoogle Scholar
  75. Mortezaee K, Minaii B, Sabbaghziarani F et al (2015) Retinoic acid as the stimulating factor for differentiation of Wharton’s jelly-mesenchymal stem cells into hepatocyte-like cells. Avicenna J Med Biotechnol 7:106–112PubMedPubMedCentralGoogle Scholar
  76. Myers SM, Johnson CP (2007) Management of children with autism spectrum disorders. Pediatrics 120(5):1162–1182PubMedCrossRefGoogle Scholar
  77. Nagamura-Inoue T, He H (2014) Umbilical cord-derived mesenchymal stem cells: their advantages and potential clinical utility. World J Stem Cells 6:195PubMedPubMedCentralCrossRefGoogle Scholar
  78. Nakamizo A, Marini F, Amano T et al (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Cancer Res 65:3307–3318PubMedGoogle Scholar
  79. Nasef A, Mathieu N, Chapel A et al (2007) Immunosuppressive effects of mesenchymal stem cells: involvement of HLA-G. Transplantation 84:231–237PubMedCrossRefGoogle Scholar
  80. Nekanti U, Rao V, Bahirvani A et al (2010) Long-term expansion and pluripotent marker array analysis of Wharton’s jelly-derived mesenchymal stem cells. Stem Cells Dev 19:117–130PubMedCrossRefGoogle Scholar
  81. Nicola M, Carlo-Stella C, Magni M et al (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843PubMedCrossRefGoogle Scholar
  82. Parry EW (1970) Some electron microscope observations on the mesenchymal structures of full-term umbilical cord. J Anat 107(Pt 3):505–518PubMedPubMedCentralGoogle Scholar
  83. Patel S, Meyer J, Greco S et al (2010) Mesenchymal stem cells protect breast cancer cells through regulatory T cells: role of mesenchymal stem cell-derived TGF-β. J Immunol 184:5885–5894PubMedCrossRefGoogle Scholar
  84. Prasad V, Lucas K, Kleiner G et al (2011) Efficacy and safety of ex vivo cultured adult human mesenchymal stem cells (Prochymal™) in pediatric patients with severe refractory acute graft-versus-host disease in a compassionate use study. Biol Blood Marrow Transplant 17:534–541PubMedCrossRefGoogle Scholar
  85. Qian L, Wu Z, Shen J (2013) Advances in the treatment of acute graft‐versus‐host disease. J Cell Mol Med 17:966–975PubMedPubMedCentralCrossRefGoogle Scholar
  86. Qiao L, Xu Z, Zhao T et al (2008) Suppression of tumorigenesis by human mesenchymal stem cells in a hepatoma model. Cell Res 18:500–507PubMedCrossRefGoogle Scholar
  87. Rachakatla R, Marini F, Weiss M et al (2007) Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther 14:828–835PubMedCrossRefGoogle Scholar
  88. Ramasamy R, Lam E, Soeiro I et al (2006) Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia 21:304–310PubMedCrossRefGoogle Scholar
  89. Ren C, Kumar S, Chanda D et al (2008) Therapeutic potential of mesenchymal stem cells producing interferon-alpha in a mouse melanoma lung metastasis model. Stem Cells 26(9):2332–2338PubMedPubMedCentralCrossRefGoogle Scholar
  90. Rockey D, Friedman SL (2006) Hepatic fibrosis and cirrhosis. In: Section I: Pathophysiology of the liver. Elsevier, Amsterdam, pp 87–109Google Scholar
  91. Salehinejad P, Alitheen N, Ali A et al (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 48:75–83PubMedCrossRefGoogle Scholar
  92. Sariboyaci AE, Demircan PC, Gacar G et al (2014) Immunomodulatory properties of pancreatic islet-derived stem cells co-cultured with T cells: does it contribute to the pathogenesis of type 1 diabetes? Exp Clin Endocrinol Diabetes 122(3):179–189PubMedCrossRefGoogle Scholar
  93. Scheers I, Lombard C, Paganelli M et al (2013) Human umbilical cord matrix stem cells maintain multilineage differentiation abilities and do not transform during long-term culture. PLoS One 8(8):e71374PubMedPubMedCentralCrossRefGoogle Scholar
  94. Schmidt D, Mol A, Breymann C et al (2006a) Living autologous heart valves engineered from human prenatally harvested progenitors. Circulation 114:I125–I131PubMedCrossRefGoogle Scholar
  95. Schmidt D, Asmis L, Odermatt B et al (2006b) Engineered living blood vessels: functional endothelia generated from human TM umbilical cord-derived progenitors. Ann Thorac Surg 82:1465–1471; discussion 1471PubMedCrossRefGoogle Scholar
  96. Shrestha C, Zhao L, Chen K, et al (2013) Enhanced healing of diabetic wounds by subcutaneous administration of human umbilical cord derived stem cells and their conditioned media. Int J Endocrinol 2013, Article ID 592454, 10 pagesGoogle Scholar
  97. Sohni A, Verfaillie C (2013) Mesenchymal stem cells migration homing and tracking. Stem Cells Int 2013, Article ID 130763, 8 pagesGoogle Scholar
  98. Song C, Li G (2011) CXCR4 and matrix metalloproteinase-2 are involved in mesenchymal stromal cell homing and engraftment to tumors. Cytotherapy 13:549–561PubMedCrossRefGoogle Scholar
  99. Stevens A, Johnson F (1922) A new eruptive fever associated with stomatitis and ophthalmia: report of two cases in children. Am J Dis Child 24:526–533CrossRefGoogle Scholar
  100. Strassburg S, Hodson N, Hill P et al (2012) Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells. PLoS One 7(3):e33739PubMedPubMedCentralCrossRefGoogle Scholar
  101. Subramanian A, Fong C-Y, 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
  102. Sun L, Wang D, Liang J et al (2010) Umbilical cord mesenchymal stem cell transplantation in severe and refractory systemic lupus erythematosus. Arthritis Rheum 62:2467–2475PubMedCrossRefGoogle Scholar
  103. Sung A, Chao N (2013) Acute graft-versus-host disease: are we close to bringing the bench to the bedside? Best Pract Res Clin Haematol 26:285–292PubMedCrossRefGoogle Scholar
  104. Terai S, Ishikawa T, Omori K et al (2006) Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells 24:2292–2298PubMedCrossRefGoogle Scholar
  105. Trépo C, Chan H, Lok A (2014) Hepatitis B virus infection. Lancet 384:2053–2063PubMedCrossRefGoogle Scholar
  106. Trivanović D, Kocić J, Mojsilović S et al (2013) Mesenchymal stem cells isolated from peripheral blood and umbilical cord Wharton’s jelly. Srp Ark Celok Lek 141:178–186CrossRefGoogle Scholar
  107. Tsai P, Fu T, Chen Y et al (2009) The therapeutic potential of human umbilical mesenchymal stem cells from Wharton’s jelly in the treatment of rat liver fibrosis. Liver Transpl 15:484–495PubMedCrossRefGoogle Scholar
  108. Underwood B, Rubinsztein D (2008) Spinocerebellar ataxias caused by polyglutamine expansions: a review of therapeutic strategies. Cerebellum 7:215–221PubMedCrossRefGoogle Scholar
  109. Walczak P, Zhang J, Gilad A et al (2008) Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem cells after transient ischemia. Stroke 39:1569–1574PubMedPubMedCentralCrossRefGoogle Scholar
  110. Wang H, Hung S, Peng S et al (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337PubMedCrossRefGoogle Scholar
  111. Wang L, Tran I, Seshareddy K et al (2009) A comparison of human bone marrow-derived mesenchymal stem cells and human umbilical cord-derived mesenchymal stromal cells for cartilage tissue engineering. Tissue Eng Part A 15:2259–2266PubMedCrossRefGoogle Scholar
  112. Wang L, Dormer N, Bonewald L, Detamore M (2010) Osteogenic differentiation of human umbilical cord mesenchymal stromal cells in polyglycolic acid scaffolds. Tissue Eng Part A 16:1937–1948PubMedCrossRefGoogle Scholar
  113. Wang Y, Fan H, Zhou B et al (2011) Fusion of human umbilical cord mesenchymal stem cells with esophageal carcinoma cells inhibits the tumorigenicity of esophageal carcinoma cells. Int J Oncol 40:370–377PubMedGoogle Scholar
  114. Weiss M, Medicetty S, Bledsoe A 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 24:781–792PubMedCrossRefGoogle Scholar
  115. Weiss M, Anderson C, Medicetty S et al (2008) Immune properties of human umbilical cord Wharton’s jelly-derived cells. Stem Cells 26:2865–2874PubMedCrossRefGoogle Scholar
  116. Wetzig A, Alaiya A, Al-Alwan M et al (2013) Differential marker expression by cultures rich in mesenchymal stem cells. BMC Cell Biol 14:54PubMedPubMedCentralCrossRefGoogle Scholar
  117. Wu Y, Chen L, Scott P, Tredget E (2007) Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 25:2648–2659PubMedCrossRefGoogle Scholar
  118. Wu K-H, Chan C-K, Tsai C et al (2011) Effective treatment of severe steroid-resistant acute graft-versus-host disease with umbilical cord-derived mesenchymal stem cells. Transplantation 91:1412PubMedCrossRefGoogle Scholar
  119. Xu G, Zhang L, Ren G et al (2007) Immunosuppressive properties of cloned bone marrow mesenchymal stem cells. Cell Res 17:240–248PubMedGoogle Scholar
  120. Yang C-C, Shih Y-H, Ko M-H et al (2008) Transplantation of human umbilical mesenchymal stem cells from Wharton’s jelly after complete transection of the rat spinal cord. PLoS One 3:e3336PubMedPubMedCentralCrossRefGoogle Scholar
  121. Yeo R, Chai R, Hian K, Kiang S (2013) Exosome: a novel and safer therapeutic refinement of mesenchymal stem cell. Exosomes Microvesicles 1:1–12CrossRefGoogle Scholar
  122. Yoo K, Jang I, Lee M et al (2009) Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunol 259:150–156PubMedCrossRefGoogle Scholar
  123. Yu B, Zhang X, Li X (2014) Exosomes derived from mesenchymal stem cells. Int J Mol Sci 15(3):4142–4157PubMedPubMedCentralCrossRefGoogle Scholar
  124. Zhang Z, Lin H, Shi M et al (2012) Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroen Hepatol 27:112–120CrossRefGoogle Scholar
  125. Zheng G, Liu Y, Jing Q, Zhang L (2015) Differentiation of human umbilical cord-derived mesenchymal stem cells into hepatocytes in vitro. Biomed Mater Eng 25(1 Suppl):145–157PubMedGoogle Scholar
  126. Zhou Y, Xu H, Xu W et al (2013) Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Amp Ther 4:34CrossRefGoogle Scholar
  127. Zhuang H, Zhang R, Zhang S et al (2015) Altered expression of microRNAs in the neuronal differentiation of human Wharton’s Jelly mesenchymal stem cells. Neurosci Lett 600:69–74PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Centre for Regenerative Medicine and Stem Cell ManufacturingLivMedCell, Liv HospitalİstanbulTurkey

Personalised recommendations