Cell and Tissue Research

, Volume 362, Issue 2, pp 367–377 | Cite as

Comparative analysis of neural differentiation potential in human mesenchymal stem cells derived from chorion and adult bone marrow

  • Reihane Ziadlou
  • Maryam ShahhoseiniEmail author
  • Fatemeh Safari
  • Forugh-Azam Sayahpour
  • Shiva Nemati
  • Mohamadreza Baghaban EslaminejadEmail author
Regular Article


The finding of a reliable and abundant source of stem cells for the replacement of missing neurons in nervous system diseases requires extensive characterization of neural-differentiation-associated markers in stem cells from various sources. Chorion-derived stem cells from the human placenta have recently been described as an abundant, ethically acceptable, and easily accessible source of cells that are not limited in the same way as bone marrow (BM) mesenchymal stem cells (MSCs). We have isolated and cultured chorion MSCs (C-MSCs) and compared their proliferative capacity, multipotency, and neural differentiation ability with BM-MSCs. C-MSCs showed a higher proliferative capacity compared with BM-MSCs. The expression and histone modification of Nestin, as a marker for neural stem/progenitor cells, was evaluated quantitatively between the two groups. The Nestin expression level in C-MSCs was significantly higher than that in BM-MSCs. Notably, modifications of lys9, lys4, and lys27 of histone H3 agreed with the remarkable higher expression of Nestin in C-MSCs than in BM-MSCs. Furthermore, after neural differentiation of MSCs upon retinoic acid induction, both immunocytochemical and flow cytometry analyses demonstrated that the expression of neural marker genes was significantly higher in neural-induced C-MSCs compared with BM-MSCs. Mature neuron marker genes were also expressed at a significantly higher level in C-MSCs than in BM-MSCs. Thus, C-MSCs have a greater potential than BM-MSCs for differentiation to neural cell lineages and can be regarded as a promising source of stem cells for the cell therapy of neurological disorders.


Chorion Bone marrow Mesenchymal stem cells Neural differentiation Human 



We thank Raha Favaedi for her kind technical support of the project.

Supplementary material

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Fig. S1

(GIF 50 kb)

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High resolution image (TIFF 483 kb)


  1. Arber S, Han B, Mendelsohn M, Smith M, Jessell TM, Sockanathan S (1999) Requirement for the homeobox gene hb9 in the consolidation of motor neuron identity. Neuron 23:659–674CrossRefPubMedGoogle Scholar
  2. Arnhold S, Klein H, Semkova I, Addicks K, Schraermeyer U (2004) Neurally selected embryonic stem cells induce tumor formation after long-term survival following engraftment into the subretinal space. Invest Ophthalmol Vis Sci 45:4251–4255CrossRefPubMedGoogle Scholar
  3. Atala A (2006) Recent developments in tissue engineering and regenerative medicine. Curr Opin Pediatr 18:167–171CrossRefPubMedGoogle Scholar
  4. Bannister AJ, Kouzarides T (2011) Regulation of chromatin by histone modifications. Cell Res 21:381–395PubMedCentralCrossRefPubMedGoogle Scholar
  5. Barker RA, Widner H (2004) Immune problems in central nervous system cell therapy. NeuroRx 1:472–481PubMedCentralCrossRefPubMedGoogle Scholar
  6. Barker RA, Jain M, Armstrong RJE, Caldwell MA (2003) Stem cells and neurological disease. J Neurol Neurosurg Psychiatry 74:553–557PubMedCentralCrossRefPubMedGoogle Scholar
  7. Bradley JA, Bolton EM, Pedersen RA (2002) Stem cell medicine encounters the immune system. Nat Rev Immunol 2:859–871CrossRefPubMedGoogle Scholar
  8. Capitelli CS, Lopes CS, Alves AC, Barbiero J, Oliveira LF, da Silva VJ, Vital MA (2014) Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson’s disease: a comparison study of mononuclear and mesenchymal stem cells. Int J Med Sci 11:1049–1064PubMedCentralCrossRefPubMedGoogle Scholar
  9. Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, Lu M, Rosenblum M (2000) Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 11:3001–3005CrossRefPubMedGoogle Scholar
  10. Collas P, Noer A, Sørensen AL (2008)Epigenetic basis for the differentiation potential of mesenchymal and embryonic stem cells. Transfus Med Hemother 35:205–215PubMedCentralCrossRefPubMedGoogle Scholar
  11. Da Silva ML, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119:2204–2213CrossRefGoogle Scholar
  12. Deng W, Obrocka M, Fischer I, Prockop DJ (2001) In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 282:148–152CrossRefPubMedGoogle Scholar
  13. Divya MS, Roshin GE, Divya TS, Rasheed VA, Santhoshkumar TR, Elizabeth KE, James J, Pillari 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 3:57PubMedCentralCrossRefPubMedGoogle Scholar
  14. Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A 94:4080–4085PubMedCentralCrossRefPubMedGoogle Scholar
  15. El-Badri NS, Hakki A, Saporta S, Liang X, Madhusodanan S, Willing AE, Sanberg CD, Sanberg PR (2006) Cord blood mesenchymal stem cells: potential use in neurological disorders. Stem Cells Dev 15:497–506CrossRefPubMedGoogle Scholar
  16. Favaedi R, Shahhoseini M, Akhoond MR (2012) Comparative epigenetic analysis of Oct4 regulatory region in RA-induced differentiated NT2 cells under adherent and non-adherent culture conditions. Mol Cell Biochem 363:129–134CrossRefPubMedGoogle Scholar
  17. Hess DC, Borlongan CV (2008) Stem cells and neuro-logical diseases. Cell Prolif 41:94–114CrossRefPubMedGoogle Scholar
  18. Ilancheran S, Moodley Y, Manuelpillai U (2009) Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta 30:2–10CrossRefPubMedGoogle Scholar
  19. Ishii T, Ohsugi K, Nakamura S, Sato K, Hashimoto M, Mikoshiba K, Sakuragawa N (1999) Gene expression of oligodendrocyte markers in human amniotic epithelial cells using neural cell-type-specific expression system. Neurosci Lett 268:131–134CrossRefPubMedGoogle Scholar
  20. Juengst E, Fossel M (2000) The ethics of embryonic stem cells—now and forever, cells without end. JAMA 284:3180–3184CrossRefPubMedGoogle Scholar
  21. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA (2010) Mesenchymal stem cells for the treatment of neurodegenerative disease. Regen Med 5:933–946PubMedCentralCrossRefPubMedGoogle Scholar
  22. Kang SK, Lee DH, Bae YC, Kim HK, Baik SY, Jung JS (2003) Improvement of neurological deficits by intracerebral transplantation of human adipose tissue derived stromal cells after cerebral ischemia in rats. Exp Neurol 183:355–366CrossRefPubMedGoogle Scholar
  23. Kern S, Eichler H, Stoeve J, Kluter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301CrossRefPubMedGoogle Scholar
  24. Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A 96:10711–10716PubMedCentralCrossRefPubMedGoogle Scholar
  25. Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705CrossRefPubMedGoogle Scholar
  26. Lee H, Kang JE, Lee JK, Bae JS, Jin HK (2013) Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann–Pick type C mouse neural stem cells by upregulation and secretion of CCL2. Hum Gene Ther 24:655–669PubMedCentralCrossRefPubMedGoogle Scholar
  27. Li C, Zhang W, Jiang X, Mao N (2007) Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 330:437–446CrossRefPubMedGoogle Scholar
  28. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408CrossRefPubMedGoogle Scholar
  29. Lunyak VV, Rosenfeld MG (2008) Epigenetic regulation of stem cell fate. Hum Mol Genet 17:R28–R36CrossRefPubMedGoogle Scholar
  30. Marcus AJ, Coyne TM, Black IB, Woodbury D (2008) Fate of amnion-derived stem cells transplanted to the fetal rat brain: migration, survival and differentiation. J Cell Mol Med 12:1256–1264PubMedCentralCrossRefPubMedGoogle Scholar
  31. Martin C, Zhang Y (2005) The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6:838–849CrossRefPubMedGoogle Scholar
  32. McLaren (2001) Ethical and social considerations of stem cell research. Nature 414:129–131CrossRefPubMedGoogle Scholar
  33. Miao Z, Jin J, Chen L, Zhu J, Huang W, Zhao J, Qian H, Zhang X (2006) Isolation of mesenchymal stem cells from human placenta: comparison with human bone marrow mesenchymal stem cells. Cell Biol Int 30:681–687CrossRefPubMedGoogle Scholar
  34. Michalczyk K, Ziman M (2005) Nestin structure and predicted function in cellular cytoskeletal organization. Histol Histopathol 20:665–671PubMedGoogle Scholar
  35. Mohamed Ariff I, Mitra A, Basu A (2012) Epigenetic regulation of self-renewal and fate determination in neural stem cells. J Neurosci Res 90:529–539CrossRefPubMedGoogle Scholar
  36. Momin EN, Mohyeldin A, Zaidi HA, Vela G, Quinones-Hinojosa A (2010) Mesenchymal stem cells: new approaches for the treatment of neurological diseases. Curr Stem Cell Res Ther 5:326–344CrossRefPubMedGoogle Scholar
  37. Park DH, Lee JH, Borlongan CV, Sanberg PR, Chung YG, Cho TH (2011) Transplantation of umbilical cord blood stem cells for treating spinal cord injury. Stem Cell Rev Rep 7:181–194CrossRefGoogle Scholar
  38. Pittinger 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 284:143–147CrossRefGoogle Scholar
  39. Portmann-Lanz CB, Baumann MU, Mueller M, Wagner AM, Weiss S, Haller O, Sager R, Reinhart U, Surbek DV (2010) Neurogenic characteristics of placental stem cells in preeclampsia. Am J Obstet Gynecol 203:399.e1-e7CrossRefGoogle Scholar
  40. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256CrossRefPubMedGoogle Scholar
  41. Shahhoseini M, Favaedi R, Baharvand H, Sharma V, Stunnenberg HG (2010a) Evidence for a dynamic role of the linker histone variant H1x during retinoic acid-induced differentiation of NT2 cells. FEBS Lett 584:4661–4664CrossRefPubMedGoogle Scholar
  42. Shahhoseini M, Taei A, Mehrjardi NZ, Salekdeh GH, Baharvand H (2010b) Epigenetic analysis of human embryonic carcinoma cells during retinoic acid-induced neural differentiation. Biochem Cell Biol 88:527–538CrossRefPubMedGoogle Scholar
  43. Shahhoseini M, Taghizadeh Z, Hatami M, Baharvand H (2013) Retinoic acid dependent histone 3 demethylation of the clustered HOX genes during neural differentiation of human embryonic stem cells. Biochem Cell Biol 91:116–122CrossRefPubMedGoogle Scholar
  44. Soncini M, Vertua E, Gibelli L, Zorzi F, Denegri M, Albertini A, Wengler GS, Parolini O (2007) Isolation and characterization of mesenchymal cells from human fetal membranes. J Tissue Eng Regen Med 1:296–305CrossRefPubMedGoogle Scholar
  45. Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926CrossRefPubMedGoogle Scholar
  46. Tropel P, Noel D, Platet N, Platet N, Legrand P, Benabid AL, Berger F (2004) Isolation and characterization of mesenchymal stem cells from adult mouse bone marrow. Exp Cell Res 295:395–406CrossRefPubMedGoogle Scholar
  47. Wislet-Gendebien S, Leprince P, Moonen G, Rogister B (2003) Regulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells. J Cell Sci 116:3295–3302CrossRefPubMedGoogle Scholar
  48. Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61:364–370CrossRefPubMedGoogle Scholar
  49. Zhang X, Soda Y, Takahashi K, Bai Y, Mitsuru A, Igura K, Satoh H, Yamaguchi S, Tani K, Tojo A, Takahashi TA (2006) Successful immortalization of mesenchymal progenitor cells derived from human placenta and the differentiation abilities of immortalized cells. Biochem Biophys Res Commun 351:853–859CrossRefPubMedGoogle Scholar
  50. Zheng YB, Gao ZL, Xie C, Zhu HP, Peng L, Chen JH, Chong YT (2008) Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study. Cell Biol Int 32:1439–1448CrossRefPubMedGoogle Scholar
  51. Zimmerman L, Parr B, Lendahl U, Cunningham M, McKay R, Gavin B, Mann J, Vassileva G, McMahon A (1994) Independent regulatory elements in the nestin gene direct trans gene expression to neural stem cells or muscle precursors. Neuron 12:11–24CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Reihane Ziadlou
    • 1
    • 2
    • 3
  • Maryam Shahhoseini
    • 1
    Email author
  • Fatemeh Safari
    • 2
  • Forugh-Azam Sayahpour
    • 2
  • Shiva Nemati
    • 2
  • Mohamadreza Baghaban Eslaminejad
    • 2
    Email author
  1. 1.Department of Genetics at Reproductive Biomedicine Research CenterRoyan Institute for Reproductive Biomedicine, ACECRTehranIran
  2. 2.Department of Stem Cells and Developmental Biology at Cell Science Research CenterRoyan Institute for Stem Cell Biology and Technology, ACECRTehranIran
  3. 3.Department of Molecular and Cellular Biology, Faculty of Basic Sciences and Advanced Technologies in BiologyUniversity of Science and CultureTehranIran

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