Skip to main content

Advertisement

Log in

Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Stem cells of fetal origin lie between embryonic and adult stem cells in terms of potentiality. Because of the ethical controversy surrounding embryonic stem cells and the relatively inferior quality of adult stem cells, the use of fetal stem cells would be an attractive option in future therapeutic applications. Here, we have investigated primitive characteristics of human umbilical-cord-derived fetal mesenchymal stem cells (UC fMSCs) during extensive expansion. We have successfully isolated and cultured UC fMSCs from all UC samples, but with two early fungal contaminations. UC fMSCs proliferated without significant evidence of morphological changes, and the average cumulative population-doubling level was over 25 for about 3 months. UC fMSCs showed the positive expression of several CD markers, known to be related to MSCs, including CD73 (SH-3, 4), CD90 (Thy-1), CD105 (SH-2), CD117 (c-kit), and CD166 (ALCAM). They demonstrated primitive properties throughout the expansion period: multilineage differentiation potentials examined by functional assays, a variety of pluripotent stem cell markers including Nanog, Oct-4, Sox-2, Rex-1, SSEA-3, SSEA-4, Tra-1–60, and Tra-1–81, minimal evidence of senescence as shown by β-galactosidase staining, and the consistent expression of telomerase activity. These results suggest that UC fMSCs have more primitive properties than adult MSCs, which might make them a useful source of MSCs for clinical applications.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Alison M, Sarraf C (1998) Hepatic stem cells. J Hepatol 29:676–682

    Article  CAS  PubMed  Google Scholar 

  • Baxter MA, Wynn RF, Jowitt SN, Wraith JE, Fairbairn LJ, Bellantuono I (2004) Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion. Stem Cells 22:675–682

    Article  CAS  PubMed  Google Scholar 

  • Bieback K, Kern S, Kluter H, Eichler H (2004) Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood. Stem Cells 22:625–634

    Article  PubMed  Google Scholar 

  • Bonab MM, Alimoghaddam K, Talebian F, Ghaffari SH, Ghavamzadeh A, Nikbin B (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7:14–20

    Article  PubMed  CAS  Google Scholar 

  • Boyer LA, Lee IT, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, Gifford DK, Melton DA, Jaenisch R, Young RA (2005) Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 122:947–956

    Article  CAS  PubMed  Google Scholar 

  • 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 4:8–20

    Article  PubMed  CAS  Google Scholar 

  • Deasy BM, Jankowski RJ, Huard J (2001) Muscle-derived stem cells: characterization and potential for cell-mediated therapy. Blood Cell Mol Dis 27:924–933

    Article  CAS  Google Scholar 

  • D’ippolito G, Schiller P, Ricordi C, Roos BA, Howard GA (1999) Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 14:1115–1122

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monlayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3:393–403

    CAS  PubMed  Google Scholar 

  • Fong CY, Richards M, Mansi N, Biswas A, Bonqso A (2007) Comparative growth behavior and characterization of stem cells from human Wharton’s jelly. Reprod Biomed Online 15:708–718

    Article  CAS  PubMed  Google Scholar 

  • Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsoninsm. Stem Cells 24:115–124

    Article  PubMed  Google Scholar 

  • Guillot PV, O’Donoghue K, Kurata H, Fisk NM (2006) Fetal stem cells: betwixt and between. Semin Reprod Med 24:340–347

    Article  CAS  PubMed  Google Scholar 

  • Guillot PV, Gotherstrom C, Kurata H, Chan J, Fisk NM (2007) Human first-trimester fetal MSC express pluripotency markers and grow faster and have longer telomeres than adult MSC. Stem Cells 25:646–652

    Article  CAS  PubMed  Google Scholar 

  • Hoynowski SM, Fry MM, Gardner BM, Leming MT, Tucker JR, Black L, Sand T, Mitchell KE (2007) Characterization and differentiation of equine umbilical cord-derived matrix cells. Biochem Biophys Res Commun 362:347–353

    Article  CAS  PubMed  Google Scholar 

  • Izadpanah R, Trygg C, Patel B, Kriedt C, Dufour J, Gimble JM, Bunnell BA (2006) Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 99:1285–1297

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 64:295–312

    Article  CAS  PubMed  Google Scholar 

  • Jo H, Park JS, Kim EM, Jung MY, Lee SH, Seong SC, Park SC, Kim HJ, Lee MC (2003) The in vitro effects of dehydroepiandrosterone on human osteoarthritic chondrocytes. Osteoarthritis Cartilage 11:585–594

    Article  CAS  PubMed  Google Scholar 

  • Jo CH, Ahn HJ, Kim HJ, Seong SC, Lee MC (2007) Surface characterization and chondrogenic differentiation of mesenchymal stromal cells derived from synovium. Cytotherapy 9:316–327

    Article  CAS  PubMed  Google Scholar 

  • 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 25:319–331

    Article  CAS  PubMed  Google Scholar 

  • Lu LL, Liu YJ, Yang SG, Zhao OJ, Wang XG, Gong W, Han ZB, Xu ZS, Lu YX, Liu D, Chen ZZ, Han ZC (2006) Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica 91:1017–1026

    CAS  PubMed  Google Scholar 

  • Mareschi K, Ferrero I, Rustichelli D, Aschero S, Gammaitoni L, Aglietta M, Madon E, Fagioli F (2006) Expansion of mesenchymal stem cells isolated from pediatric and adult donor bone marrow. J Cell Biochem 97:744–754

    Article  CAS  PubMed  Google Scholar 

  • Mendes SC, Tibbe JM, Veenhof M, Bakker K, Both S, Platenburg PP, Oner FC, De Bruijn JD, Blitterswijk CAV (2002) Bone tissue-engineered implants using human bone marrow stromal cells: effect of culture conditions and donor age. Tissue Eng 8:911–920

    Article  CAS  PubMed  Google Scholar 

  • McGuckin CP, Forraz N, Baradez MO, Navran S, Zhao J, Urban R, Tilton R, Denner L (2005) Production of stem cells with embryonic characteristics from human umbilical cord blood. Cell Prolif 38:245–255

    Article  CAS  PubMed  Google Scholar 

  • Pittenger MD, 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 284:143–147

    Article  CAS  PubMed  Google Scholar 

  • Pojda Z, Machaj EK, Oldak T, Gajkowska A, Jastrzewsk M (2005) Nonhematopoietic stem cells of fetal origin—how much of today’s enthusiasm will pass the time test? Folia Histochem Cytobiol 43:209–212

    PubMed  Google Scholar 

  • Rao MS, Matton MP (2001) Stem cells and aging: expanding the possibilities. Mech Ageing Dev 122:12–34

    Article  Google Scholar 

  • Romanov YA, Svintsjtskaya VA, Sminov VN (2003) Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 21:105–110

    Article  PubMed  Google Scholar 

  • Roura S, Farre J, Soler-Botija C, Llach A, Hove-Madsen L, Cairo JJ, Godia F, Cinca J, Bayes-Genis A (2006) Effect of aging on the pluripotential capacity of human CD105+ mesenchymal stem cells. Eur J Heart Fail 8:555–563

    Article  CAS  PubMed  Google Scholar 

  • Rubio D, Garci-Castro J, Martin MC, Fuente R de la, Cigudosa JC, Lloyd AC, Bernad A (2005) Spontaneous human adult stem cell transformation. Cancer Res 5:3035–3039

    Google Scholar 

  • Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE (2005) Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 23:220–229

    Article  PubMed  Google Scholar 

  • Secco M, Zucconi E, Vieira NM, Fogaca LLQ, Cerqueira A, Carvalho MDF, Jazedje T, Okamoto OK, Muotri AR, Zatz M (2008) Multipotent stem cells from umbilical cord: cord is richer than blood. Stem Cells 26:146–150

    Article  CAS  PubMed  Google Scholar 

  • Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decrease maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33:919–926

    Article  PubMed  Google Scholar 

  • Stolzing A, Scutt A (2006) Age-related impairment of mesenchymal progenitor cell function. Aging Cell 5:213–244

    Article  CAS  PubMed  Google Scholar 

  • Vidal MA, Kilroy GE, Johnson JR, Lopez MJ, Moore RM, Gimble JM (2006) Cell growth characteristics and differentiation frequency of adherent equine bone marrow-derived mesenchymal stromal cells: adipogenic and osteogenic capacity. Vet Surg 35:601–610

    Article  PubMed  Google Scholar 

  • Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu Y, Lai M, Chen C (2004) Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 22:1330–1337

    Article  PubMed  Google Scholar 

  • Wang Y, Huso DL, Harrington J, Kellner J, Jeong DK, Turney J, McNiece IK (2005) Outgrowth of a transformed cell population derived from normal human BM mesenchymal stem cell culture. Cytotherapy 7:509–519

    Article  CAS  PubMed  Google Scholar 

  • Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao M, 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 24:781–792

    Article  CAS  PubMed  Google Scholar 

  • Wexler SA, Donaldson C, Denning-Kendal 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 121:368–374

    Article  PubMed  Google Scholar 

  • Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I (2007) Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res 327:449–462

    Article  CAS  PubMed  Google Scholar 

  • Zimmermann S, Voss M, Kaiser S, Kapp U, Waller CF, Martens UM (2004) Lack of telomerase activity in human mesenchymal stem cells. Leukemia 17:1146–1149

    Article  CAS  Google Scholar 

  • Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhain P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211–228

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kang-Sup Yoon.

Additional information

This work was supported by the Seoul R&BD Program (10548).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jo, C.H., Kim, OS., Park, EY. et al. Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion. Cell Tissue Res 334, 423–433 (2008). https://doi.org/10.1007/s00441-008-0696-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-008-0696-3

Keywords

Navigation