Skip to main content

Advertisement

SpringerLink
Log in

Multipotent properties of myofibroblast cells derived from human placenta

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

Abstract

Human uterine fibroblasts (HuF) isolated from the maternal part (decidua parietalis) of a term placenta provide a useful model of in vitro cell differentiation into decidual cells (decidualization, a critical process for successful pregnancy). After isolation, the cells adhere to plastic and have either a small round or spindle-shaped morphology that later changes into a flattened pattern in culture. HuF robustly proliferate in culture until passage 20 and form colonies when plated at low densities. The cells express the mesenchymal cell markers fibronectin, integrin-β1, ICAM-1 (CD54), and collagen I. Flow cytometry of HuF has detected the presence of CD34, a marker of the hematopoietic stem cell lineage, and an absence of CD10, CD11b/Mac, CD14, CD45, and HLA type II. Furthermore, they also express the pluripotency markers SSEA-1, SSEA-4, Oct-4, Stro-1, and TRA-1–81 as detected by confocal microscopy. Treatment for 14–21 days with differentiation-inducing media leads to the differentiation of HuF into osteoblasts, adipocytes, and chondrocytes. The presence of α-smooth muscle actin, calponin, and myosin light-chain kinase in cultured HuF implies their similarity to myofibroblasts. Treatment of the HuF with dimethyl sufoxide causes reversion to the spindle-shaped morphology and a loss of myofibroblast characteristics, suggesting a switch into a less differentiated phenotype. The unique abilities of HuF to exhibit multipotency, even with myofibroblast characteristics, and their ready availability and low maintenance requirements make them an interesting cell model for further exploration as a possible tool for regenerative medicine.

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

Access this article

Log in via an institution

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
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Battula VL, Bareiss PM, Treml S, Conrad S, Albert I, Hojak S, Abele H, Schewe B, Just L, Skutella T, Bühring HJ (2007) Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF-containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation. Differentiation 75:279–291

    Article  PubMed  CAS  Google Scholar 

  • Brar AK, Handwerger S, Kessler CA, Aronow BJ (2001) Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization. Physiol Genomics 7:135–148

    PubMed  CAS  Google Scholar 

  • Colter DC, Class R, DiGirolamo CM, Prockop DJ (2000) Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proc Natl Acad Sci USA 97:3213–3218

    Article  PubMed  CAS  Google Scholar 

  • Colter DC, Sekiya I, Prockop DJ (2001) Identification of a subpopulation of rapidly self-renewing and multipotential adult stem cells in colonies of human marrow stromal cells. Proc Natl Acad Sci USA 98:7841–7845

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • De Lanerolle P, Adelstein RS, Feramisco JR, Burridge K (1981) Characterization of antibodies to smooth muscle myosin kinase and their use in localizing myosin kinase in nonmuscle cells. Proc Natl Acad Sci USA 78:4738–4742

    Article  PubMed  Google Scholar 

  • Delo DM, De Coppi P, Bartsch G, Atala A (2006) Amniotic fluid and placental stem cells. Methods Enzymol 419:426–438

    Article  PubMed  CAS  Google Scholar 

  • Eyal O, Jomain JB, Kessler C, Goffin V, Handwerger S (2007) Autocrine prolactin inhibits human uterine decidualization: a novel role for prolactin. Biol Reprod 76:777–783

    Article  PubMed  CAS  Google Scholar 

  • Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503

    Article  PubMed  CAS  Google Scholar 

  • García-Pacheco JM, Oliver C, Kimatrai M, Blanco FJ, Olivares EG (2001) Human decidual stromal cells express CD34 and STRO-1 and are related to bone marrow stromal precursors. Mol Hum Reprod 7:1151–1157

    Article  PubMed  Google Scholar 

  • Hegner B, Weber M, Dragun D, Schulze-Lohoff E (2005) Differential regulation of smooth muscle markers in human bone marrow-derived mesenchymal stem cells. J Hypertens 23:1191–1202

    Article  PubMed  CAS  Google Scholar 

  • Hinz B, Dugina V, Ballestrem C, Wehrle-Haller B, Chaponnier C (2003) Alpha-smooth muscle actin is crucial for focal adhesion maturation in myofibroblasts. Mol Biol Cell 14:2508–2519

    Article  PubMed  CAS  Google Scholar 

  • Ihnatovych I, Hu W, Martin JL, Fazleabas AT, De Lanerolle P, Strakova Z (2007) Increased phosphorylation of myosin light chain prevents in vitro decidualization. Endocrinology 148:3176–3184

    Article  PubMed  CAS  Google Scholar 

  • In’t Anker PS, Scherjon SA, Kleijburg-van der Keur C, Groot-Swings GM de, Claas FH, Fibbe WE, Kanhai HH (2004) Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. Stem Cells 22:1338–1345

    Article  Google Scholar 

  • Kessler CA, Schroeder JK, Brar AK, Handwerger S (2006) Transcription factor ETS1 is critical for human uterine decidualization. Mol Hum Reprod 12:71–76

    Article  PubMed  CAS  Google Scholar 

  • Khaitlina SY (2001) Functional specificity of actin isoforms. Int Rev Cytol 202:35–98

    Article  PubMed  CAS  Google Scholar 

  • Kim JJ, Jaffe RC, Fazleabas AT (1998) Comparative studies on the in vitro decidualization process in the baboon (Papio anubis) and human. Biol Reprod 59:160–168

    Article  PubMed  CAS  Google Scholar 

  • Kim J, Lee Y, Kim H, Hwang KJ, Kwon HC, Kim SK, Cho DJ, Kang SG, You J (2007) Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells. Cell Prolif 40:75–90

    Article  PubMed  CAS  Google Scholar 

  • Kimatrai M, Oliver C, Abadía-Molina AC, García-Pacheco JM, Olivares EG (2003) Contractile activity of human decidual stromal cells. J Clin Endocrinol Metab 88:844–849

    Article  PubMed  CAS  Google Scholar 

  • Larson BL, Vuoristo JT, Cui JG, Prockop DJ (2004) Adipogenic differentiation of human adult stem cells from bone marrow stroma (MSCs). J Bone Miner Res 19:256–264

    Article  PubMed  CAS  Google Scholar 

  • Li CD, Zhang WY, Li HL, Jiang XX, Zhang Y, Tang PH, Mao N (2005) Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation. Cell Res 15:539–547

    Article  PubMed  CAS  Google Scholar 

  • Markoff E, Zeitler P, Peleg S, Handwerger S (1983) Characterization of the synthesis and release of prolactin by an enriched fraction of human decidual cells. J Clin Endocrinol Metab 56:962–968

    Article  PubMed  CAS  Google Scholar 

  • Moldwin RM, Evans RJ, Stanford EJ, Rosenberg MT (2007) Rational approaches to the treatment of patients with interstitial cystitis. Urology 69:73–81

    Article  PubMed  Google Scholar 

  • Montes MJ, Alemán P, García-Tortosa C, Borja C, Ruiz C, García-Olivares E (1996) Cultured human decidual stromal cells express antigens associated with hematopoietic cells. J Reprod Immunol 30:53–66

    Article  PubMed  CAS  Google Scholar 

  • Oliver C, Montes MJ, Galindo JA, Ruiz C, Olivares EG (1999) Human decidual stromal cells express alpha-smooth muscle actin and show ultrastructural similarities with myofibroblasts. Hum Reprod 14:1599–1605

    Article  PubMed  CAS  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

  • Portmann-Lanz CB, Schoeberlein A, Huber A, Sager R, Malek A, Holzgreve W, Surbek DV (2006) Placental mesenchymal stem cells as potential autologous graft for pre- and perinatal neuroregeneration. Am J Obstet Gynecol 194:664–673

    Article  PubMed  CAS  Google Scholar 

  • Prockop DJ, Sekiya I, Colter DC (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3:393–396

    Article  PubMed  CAS  Google Scholar 

  • Richards RG, Brar AK, Frank GR, Hartman SM, Jikihara H (1995) Fibroblast cells from term human decidua closely resemble endometrial stromal cells: induction of prolactin and insulin-like growth factor binding protein-1 expression. Biol Reprod 52:609–615

    Article  PubMed  CAS  Google Scholar 

  • Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65:1035–1041

    Article  PubMed  CAS  Google Scholar 

  • Seshi B, Kumar S, Sellers D (2000) Human bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages. Blood Cells Mol Dis 26:234–246

    Article  PubMed  CAS  Google Scholar 

  • Silva WA, Covas DT, Panepucci RA, Proto-Siqueira R, Siufi JL, Zanette DL, Santos AR, Zago MA (2003) The profile of gene expression of human marrow mesenchymal stem cells. Stem Cells 21:661–669

    Article  PubMed  CAS  Google Scholar 

  • Strakova Z, Srisuparp S, Fazleabas AT (2000) Interleukin-1b induces the expression of insulin-like growth factor binding protein-1 during decidualization in the primate. Endocrinology 141:4664–4670

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Zohar R, McCulloch CA (2006) Multiple roles of alpha-smooth muscle actin in mechanotransduction. Exp Cell Res 312:205–214

    Article  PubMed  CAS  Google Scholar 

  • Yen BL, Huang HI, Chien CC, Jui HY, Ko BS, Yao M, Shun CT, Yen ML, Lee MC, Chen YC (2005) Isolation of multipotent cells from human term placenta. Stem Cells 23:3–9

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Li C, Jiang X, Zhang S, Wu Y, Liu B, Tang P, Mao N (2004) Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp Hematol 32:657–664

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank S. Ferguson-Gottschall for obtaining placenta and cell preparations, P. Mavrogianis for expert technical assistance with histology, and Dr. K. Narayanan for helpful technical advice.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of Illinois at Chicago, 820 South Wood Street, M/C 808, Chicago, IL 60612-7313, USA

    Zuzana Strakova, Mark Livak, Monika Krezalek & Ivanna Ihnatovych

Authors
  1. Zuzana Strakova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Livak
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monika Krezalek
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ivanna Ihnatovych
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zuzana Strakova.

Additional information

This work was supported by National Institutes of Health Grant HD-44713 (to Z.S.).

Electronic supplementary material

Below is the link to the electronic supplementary material.

Fig. S1

Live and dead cells estimated by Trypan Blue cell viability assay in 6-well plates (d1-d8 day 1 to day 8). *P<0.05 in comparison with control (ppt 124 kb)

Fig. S2

Cell viability estimated by the CellTiter 96 AQueous One Solution Cell Proliferation Assay (Promega, Madison, Wis.). Cells were plated in 96-well plates (five wells for each treatment), and DMSO (D; 0.1%, 0.5%, 1.25%, 2.5%) was addedto confluent cells for the indicated times (d1-d8 day 1 to day 8). The viability of cells was estimated by absorbance (490 nm) values at 1 hafter addition of CellTiter 96 Aqueous One Solution reagent and subtraction of background values (no cells). *P<0.05 in comparison with control (ppt 93.5 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Strakova, Z., Livak, M., Krezalek, M. et al. Multipotent properties of myofibroblast cells derived from human placenta. Cell Tissue Res 332, 479–488 (2008). https://doi.org/10.1007/s00441-008-0604-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-008-0604-x

Keywords

Search

Navigation