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.
Similar content being viewed by others
References
Alison M, Sarraf C (1998) Hepatic stem cells. J Hepatol 29:676–682
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
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
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
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
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
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
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
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
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
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
Guillot PV, O’Donoghue K, Kurata H, Fisk NM (2006) Fetal stem cells: betwixt and between. Semin Reprod Med 24:340–347
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
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
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
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
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
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
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
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
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
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
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
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
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
Rao MS, Matton MP (2001) Stem cells and aging: expanding the possibilities. Mech Ageing Dev 122:12–34
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
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
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
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
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
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
Stolzing A, Scutt A (2006) Age-related impairment of mesenchymal progenitor cell function. Aging Cell 5:213–244
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by the Seoul R&BD Program (10548).
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-008-0696-3