Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pre-Clinical Studies

Effects of human placental serum on proliferation and morphology of human adipose tissue-derived stem cells

Abstract

Media used for tissue culture may have significant effects on the growth and morphology of the adipose tissue-derived stem cells (ADSCs). As fetal bovine serum (FBS) may induce an immunological reaction and health risks, this study was designed to evaluate and compare the effects of human placental serum (HPS) on the proliferation and morphology of hADSCs. We cultured hADSCs for at least three passages in four different culture media containing either FBS, HPS, autologous serum (AS) or human allogeneic serum (HAS). Morphological and immunophenotypic characteristics, as well as proliferation rates of the hADSCs were determined. The rates of proliferation of hADSCs seemed as follows: ASHPS>HAS>>FBS. Morphologically, hADSCs isolated and expanded in medium containing HPS were similar to those grown in medium containing AS, whereas the morphology of cells cultured in human sera was different in comparison with FBS-ADSCs cultures. The immunophenotypic markers of hADSCs grown up in medium containing placental serum such as CD44+, CD90+ and CD105+, were similar to hADSCs grown up in media containing other sera. These results indicate that medium enriched with HPS provided a better microenvironment for hADSCs in comparison with medium enriched with commercially available FBS, and other human sera.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

  2. Barry FP, Murphy JM . Mesenchymal stem cells: clinical applications and biological characterization. Int J Biochem Cell Biol 2004; 136: 568–584.

    Article  Google Scholar 

  3. Awad HA, Wickham MQ, Leddy HAG, Gimble JM, Guilak F . Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 2004; 25: 3211–3222.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. De Angelis L, Berghella L, Coletta M, Lattanzi L, Zanchi M, De Angelis MG et al. Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration. J Cell Biol 1999; 147: 869–878.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Miura M, Gronthos S, Zhao M, Lu B, Fisher LW, Robey PG et al. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci USA 2003; 100: 5807–5812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sottile V, Halleux C, Bassilana F, Keller H, Seuwen K . Stem cell characteristics of human trabecular bone-derived cells. Bone 2002; 30: 699–704.

    Article  CAS  PubMed  Google Scholar 

  8. Banfi A, Bianchi G, Galotto M, Cancedda R, Quarto R . Bone marrow stromal damage after chemo/radiotherapy: occurrence, consequences and possibilities of treatment. Leuk Lymphoma 2001; 42: 863–870.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  10. Muschler GF, Nitto H, Boehm CA, Easley KA . Age- and gender related changes in the cellularity of human bone marrow and the prevalence of osteoblastic progenitors. J Orthop Res 2001; 19: 117–125.

    Article  CAS  PubMed  Google Scholar 

  11. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI et al. 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 2000; 18: 307–316.

    Article  CAS  PubMed  Google Scholar 

  12. Siniscalco D, Sullo N, Maione S, Rossi F, D’Agostino B . Stem cell therapy: the great promise in lung disease. Ther Adv Respir Dis 2008; 2: 173–177.

    Article  PubMed  Google Scholar 

  13. Cheon SJ, Kim J, Lee JS . Effects of growth factors and kinase inhibitors on the properties of human adipose-stromal cells in different culture conditions. Cell Biol Int 2008; 32: 784–791.

    Article  CAS  PubMed  Google Scholar 

  14. Prockop DJ . Marrow stromal cells as stem cells for continual renewal of nonhematopoietic tissues and as potential vectors for gene therapy. J Cell Biochem Suppl 1998; 30-31: 284–285.

    Article  CAS  PubMed  Google Scholar 

  15. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY et al. Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA 2002; 99: 8932–8937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M et al. Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 1999; 5: 309–313.

    Article  CAS  PubMed  Google Scholar 

  17. Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W . Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 2002; 30: 215–222.

    Article  CAS  PubMed  Google Scholar 

  18. Bai L, Caplan A, Lennon D, Miller RH . Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate. Neurochem Res 2007; 32: 353–362.

    Article  CAS  PubMed  Google Scholar 

  19. Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF . FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 2005; 203: 398–409.

    Article  CAS  PubMed  Google Scholar 

  20. Phinney DG, Prockop DJ . State of Transdifferentiation and Modes of Tissue Repair. Stem Cells 2007; 25: 2896–2902.

    Article  PubMed  Google Scholar 

  21. Lange C, Cakirolu F, Spiess AN, Cappallo-Obermann H, Dierlamm J, Zander AR . Accelerated and Safe Expansion of Human Mesenchymal Stromal Cells in Animal Serum-Free Medium for Transplantation and Regenerative Medicine. J Cell Physiol 2007; 213: 18–26.

    Article  CAS  PubMed  Google Scholar 

  22. Prockop DJ . Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71–74.

    Article  CAS  PubMed  Google Scholar 

  23. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143–147.

    Article  CAS  PubMed  Google Scholar 

  24. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000; 6: 1282–1286.

    Article  CAS  PubMed  Google Scholar 

  25. Toma JG, Akhavan M, Fernandes KJ, Barnabe-Heider F, Sadikot A, Kaplan DR . Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature Cell Biol 2001; 3: 778–784.

    Article  CAS  PubMed  Google Scholar 

  26. Kim SJ, Cho HH, Kim YJ, Seo SY, Kim HN, Lee JB et al. Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice. Biochem Biophys Res Commun 2005; 329: 25–31.

    Article  CAS  PubMed  Google Scholar 

  27. Mackensen A, Drager R, Schlesier M, Mertelsmann R, Lindemann A . Presence of IgE antibodies to bovine serum albumin in a patient developing anaphylaxis after vaccination with human peptide-pulsed dendritic cells. Cancer Immunol Immunother 2000; 49: 152–156.

    Article  CAS  PubMed  Google Scholar 

  28. Selvaggi TA, Walker RE, Fleisher TA . Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood 1997; 89: 776–779.

    CAS  PubMed  Google Scholar 

  29. Tuschong L, Soenen SL, Blaese RM, Candotti F, Muul LM . Immune response to fetal calf serum by two adenosine deaminase-deficient patients after T cell gene therapy. Hum Gene Ther 2002; 13: 1605–1610.

    Article  CAS  PubMed  Google Scholar 

  30. Spees JL, Gregory CA, Singh H, Tucker HA, Peister A, Lynch PJ et al. Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells forcell and gene therapy. Mol Ther 2004; 9: 747–756.

    Article  CAS  PubMed  Google Scholar 

  31. Shetty P, Bharucha K, Tanavde V . Human umbilical cord blood serum can replace fetal bovine serum in the culture of mesenchymal stem cells. Cell Biol Int 2007; 31: 293–298.

    Article  CAS  PubMed  Google Scholar 

  32. Mannello F, Tonti GA . Concise review: No breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold!. Stem Cells 2007; 25: 1603–1609.

    Article  CAS  PubMed  Google Scholar 

  33. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P et al. Multilineage cells from human adipose tissue: Implications for cell-based therapies. Tissue Eng 2001; 7: 211–218.

    Article  CAS  PubMed  Google Scholar 

  34. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ . Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 2002; 20: 530–541.

    Article  PubMed  Google Scholar 

  35. Neuhuber B, Swanger SA, Howard L, Mackay A, Fischer I . Effects of plating density and culture time on bone marrow stromal cell characteristics. Exp Hematol 2008; 36: 1176–1185.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Choi SC, Kim SJ, Choi JH, Park CY, Shim WJ, Lim DS . Fibroblast growth factor-2 and -4 promote the proliferation of bone marrow mesenchymal stem cells by the activation of the PI3K-Akt and ERK1/2 signaling pathways. Stem Cells Dev 2008; 17: 725–736.

    Article  CAS  PubMed  Google Scholar 

  37. Majore N, Moretti P, Hass R, Kasper C . Identification of subpopulations in mesenchymal stem cell-like cultures from human umbilical cord. Cell Commun Signal 2009; 7: 6.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Colter DC, Sekiya I, Prockop DJ . Identification of a subpopulation of rapidly selfrenewing and multipotential adult stem cells in colonies of human marrow stromal cells. PNAS 2001; 98: 7841–7845.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Bianco P, Gehron Robey P . Marrow stromal stem cells. J Clin Invest 2000; 105: 1663–1668.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Javazon EJ, Colter DC, Schwarz EJ, Prockop DJ . Rat marrow stromal cells are more sensitive to plating density and expand more rapidly from single-cell-derived colonies than human marrow stromal cells. Stem Cells 2001; 19: 219–225.

    Article  CAS  PubMed  Google Scholar 

  41. Shahdadfar A, Fronsdal K, Haug T, Reinholt FP, Brinchmann JE . In vitro expansion of human mesenchymal stem cells: Choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem Cells 2005; 23: 1357–1366.

    Article  CAS  PubMed  Google Scholar 

  42. Baghaban Eslaminejad M, Rouhi L, Arabnajafi M, Baharvand H . Rat marrow-derived mesenchymal stem cells developed in a medium supplemented with the autologous versus bovine serum. Cell Biol Int 2009; 20: 1–10.

    Google Scholar 

  43. Ikada Y . Tissue Engineering: Fundamentals and Applications, 1st edn. Academic Press: Suzuka, 2006.

    Google Scholar 

  44. Engler AJ, Sen S, Sweeney HL, Discher DE . Matrix elasticity directs stem cell lineage specification. Cell 2006; 126: 677–689.

    Article  CAS  PubMed  Google Scholar 

  45. Lindroos B, Boucher S, Chase L, Kuokkanen H, Huhtala H, Haataja R et al. Serum-free, xeno-free culture media maintain the proliferation rate and multipotentiality of adipose stem cells in vitro. Cytotherapy 2009; 11: 958–972.

    Article  CAS  PubMed  Google Scholar 

  46. Mannello F, Tonti GA . Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold!. Stem Cells 2007; 25: 1603–1609.

    Article  CAS  PubMed  Google Scholar 

  47. Hill DJ, Tevaarwerk GJ, Arany E, Kilkenny D, Gregory M, Langford KS et al. Fibroblast growth factor-2 (FGF-2) is present in maternal and cord serum, and in the mother is associated with a binding protein immunologically related to the FGF receptor-1. J Clin Endocrinol Metab 1995; 80: 1822–1831.

    CAS  PubMed  Google Scholar 

  48. Arany E, Hill DJ . Fibroblast growth factor-2 and fibroblast growth factor receptor-1 mRNA expression and peptide localization in placentae from normal and diabetic pregnancies. Placenta 1998; 19: 133–142.

    Article  CAS  PubMed  Google Scholar 

  49. Nimura A, Muneta T, Koga H, Mochizuki T, Suzuki K, Makino H et al. Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum 2008; 58: 501–510.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grant of the Isfahan University of Medical Sciences (Grant no. 288194). We wish to thank Dr Simon Nevin and Petra Sedlak from the University of Queensland, Australia for helpful comments on the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to A Esmaeili or E Esfandiari.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shafaei, H., Esmaeili, A., Mardani, M. et al. Effects of human placental serum on proliferation and morphology of human adipose tissue-derived stem cells. Bone Marrow Transplant 46, 1464–1471 (2011). https://doi.org/10.1038/bmt.2010.313

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.313

Keywords

This article is cited by

Search

Quick links