Skip to main content

Advertisement

Log in

Mesenchymal progenitor cells in the human umbilical cord

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Mesenchymal progenitor or stem cells (MPCs) isolated from fetal blood, liver, and bone marrow are a population of multipotential cells that can proliferate and differentiate into multiple mesodermal tissues including bone, cartilage, muscle, ligament, tendon, fat, and stroma. The objective of this study was to isolate and characterize MPCs in the human umbilical cord. The suspensions of endothelial and subendothelial cells in cord vein were collected and cultured in M199 supplemented with 10% fetal bovine serum (FBS). Of 50 umbilical cord samples, 3 had numerous fibroblastoid cells morphologically distinguishable from endothelial cells. Fibroblastic cells displayed lack of expression of vWF, Flk-1, and PECAM-1, indicating the endothelial cell-specific marker. To investigate the differentiation potentials, the cells were cultured in adipogenic or osteogenic medium for 2 weeks. Fibroblast-like cells treated with adipogenic supplementation showed Oil red O-positive staining and expressed adipsin, FABP4, LPL, and PPARγ2 genes by reverse transcriptase polymerase chain reaction (RT-PCR). In osteogenic differentiation, alkaline phosphatase activity and calcium accumulation were detected. RT-PCR studies determined that Cx43, osteopontin, and Runx2 genes were expressed in the osteogenic cultures. Among three cell lines cultured continuously for passage 10, two had normal karyotypes; however, one retained a karyotype of mos 46,XY[19]/47,XY,+mar[3]. These observations suggest that MPCs are present in human umbilical cord and possess several typical traits of MPCs.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Donovan PJ, Gearhart J (2001) The end of the beginning for pluripotent stem cells. Nature 414:92–97

    Article  Google Scholar 

  2. 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 284:143–147

    Article  CAS  PubMed  Google Scholar 

  3. Negishi Y, Kudo A, Obinata A, Kawashima K, Hirano H, Yanai N, Obinata M, Endo H (2000) Multipotency of a bone marrow stromal cell line, TBR31-2, established from ts-SV40 T antigen gene transgenic mice. Biochem Biophys Res Commun 268:450–455

    Article  Google Scholar 

  4. 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 164:247–256

    Article  Google Scholar 

  5. Conget PA, Minguell JJ (1999) Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181:67–73

    Article  Google Scholar 

  6. Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19:180–192

    Article  Google Scholar 

  7. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE, Brenner MK (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313

    Article  Google Scholar 

  8. 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 96:10711–10716

    Article  Google Scholar 

  9. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS (2000) Liver from bone marrow in humans. Hepatology 32:11–16

    Article  Google Scholar 

  10. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705

    Article  Google Scholar 

  11. Pereboeva L, Komarova S, Mikheeva G, Krasnykh V, Curiel DT (2003) Approaches to utilize mesenchymal progenitor cells as cellular vehicles. Stem Cells 21:389–404

    Article  Google Scholar 

  12. De Bari C, Dell’Accio F, Vandenabeele F, Vermeesch JR, Raymackers JM, Luyten FP (2003) Skeletal muscle repair by adult human mesenchymal stem cells from synovial membrane. J Cell Biol 160:909–918

    Article  Google Scholar 

  13. Noort WA, Kruisselbrink AB, in’t Anker PS, Kruger M, van Bezooijen RL, de Paus RA, Heemskerk MH, Lowik CW, Falkenburg JH, Willemze R, Fibbe WE (2002) Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol 30:870–878

    Article  Google Scholar 

  14. Erickson GR, Gimble JM, Franklin DM, Rice HE, Awad H, Guilak F (2002) Chondrogenic potential of adipose tissue-derived stromal cells in vitro and in vivo. Biochem Biophys Res Commun 290:763–769

    Article  Google Scholar 

  15. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, Maini RN (2000) Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2:477–488

    Article  Google Scholar 

  16. Kuznetsov SA, Mankani MH, Gronthos S, Satomura K, Bianco P, Robey PG (2001) Circulating skeletal stem cells. J Cell Biol 153:1133–1140

    Article  Google Scholar 

  17. Erices A, Conget P, Minguell JJ (2000) Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 109:235–242

    Article  Google Scholar 

  18. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675

    Article  Google Scholar 

  19. Campagnoli C, Roberts IA, Kumar S, Bennett PR, Bellantuono I, Fisk NM (2001) Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 98:2396–2402

    Article  Google Scholar 

  20. Romanov YA, Svintsitskaya VA, Smirnov 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  Google Scholar 

  21. Lazarus HM, Haynesworth SE, Gerson SL, Caplan AI (1997) Human bone marrow-derived mesenchymal (stromal) progenitor cells (MPCs) cannot be recovered from peripheral blood progenitor cell collections. J Hematother 6:447–455

    CAS  PubMed  Google Scholar 

  22. 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 121:368–374

    PubMed  Google Scholar 

  23. Mareschi K, Biasin E, Piacibello W, Aglietta M, Madon E, Fagioli F (2001) Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood. Haematologica 86:1099–1100

    CAS  PubMed  Google Scholar 

  24. Marin V, Kaplanski G, Gres S, Farnarier C, Bongrand P (2001) Endothelial cell culture: protocol to obtain and cultivate human umbilical endothelial cells. J Immunol Methods 254:183–190

    Article  Google Scholar 

  25. Ailhaud G, Grimaldi P, Negrel R (1992) Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr 12:207–233

    Article  Google Scholar 

  26. Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL (1999) Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630–1638

    Article  Google Scholar 

  27. Mandrup S, Lane MD (1997) Regulating adipogenesis. J Biol Chem 272:5367–5370

    Article  Google Scholar 

  28. Schirrmacher K, Schmitz I, Winterhager E, Traub O, Brummer F, Jones D, Bingmann D (1992) Characterization of gap junctions between osteoblast-like cells in culture. Calcif Tissue Int 51:285–290

    CAS  PubMed  Google Scholar 

  29. Denhardt DT, Guo X (1993) Osteopontin: a protein with diverse functions. FASEB J 7:1475–1482

    CAS  PubMed  Google Scholar 

  30. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764

    Article  CAS  Google Scholar 

  31. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18:307–316

    CAS  PubMed  Google Scholar 

  32. Fuchs JR, Hannouche D, Terada S, Vacanti JP, Fauza DO (2003) Fetal tracheal augmentation with cartilage engineered from bone marrow-derived mesenchymal progenitor cells. J Pediatr Surg 38:984–987

    Article  Google Scholar 

  33. Johnson TE, Umbenhauer DR, Hill R, Bradt C, Mueller SN, Levine EM, Nichols WW (1992) Karyotypic and phenotypic changes during in vitro aging of human endothelial cells. J Cell Physiol 150:17–27

    CAS  PubMed  Google Scholar 

  34. Zhang L, Aviv H, Gardner JP, Okuda K, Patel S, Kimura M, Bardeguez A, Aviv A (2000) Loss of chromosome 13 in cultured human vascular endothelial cells. Exp Cell Res 260:357–364

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by a Grant No. C-A3-210-1 from the Samsung Biomedical Research Institute, Korea.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to H. M. Ryu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, J.W., Kim, S.Y., Park, S.Y. et al. Mesenchymal progenitor cells in the human umbilical cord. Ann Hematol 83, 733–738 (2004). https://doi.org/10.1007/s00277-004-0918-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-004-0918-z

Keywords

Navigation