Skip to main content
Log in

Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells

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

Abstract

Evidence has emerged that mesenchymal stem cells (MSCs) represent a promising cell population for supporting new clinical cellular therapies. Currently, bone marrow represents the main source of MSCs, but their differentiation capacity declines with age. We have identified possible novel multilineage mesenchymal cells from human placenta. In addition to their multilineage differentiation, they have a direct immunosuppressive effect on proliferation of T lymphocytes from human adult peripheral blood (PB) and umbilical cord blood (UCB) in vitro. This immunoregulatory feature strongly implies that they have a potential application in allograft transplantation. Since placenta and UCB can be obtained from the same donor, placenta is an attractive source of MSCs for co-transplantation in conjunction with UCB-derived hematopoietic stem cells to reduce the potential of graft-versus-host disease in recipients. However, the way that they modulate the immune system is unclear. In this investigation, we have addressed the effects of human placental MSCs on various subtypes of UCB-derived and PB-derived T lymphocytes.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Aggarwal S, Pittenger M (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    Article  PubMed  CAS  Google Scholar 

  • Augello A, Tasso R, Negrini S, Amateis A, Indiveri F, Cancedda R, Pennesi G (2005) Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur J Immunol 35:1482–1490

    Article  PubMed  CAS  Google Scholar 

  • Bancroft JD, Cook HC (1984) Manual of histological techniques. Churchill Livingstone, Edinburgh

    Google Scholar 

  • Barry F, Boynton R, Haynesworth S, Murphy J, Zaia J (1999) The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105). Biochem Biophys Res Commun 265:134–139

    Article  PubMed  CAS  Google Scholar 

  • Barry F, Boynton R, Murphy M, Haynesworth S, Zaia J (2001) The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells. Biochem Biophys Res Commun 289:519–524

    Article  PubMed  CAS  Google Scholar 

  • Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R (2002) Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 30:42–48

    Article  PubMed  Google Scholar 

  • Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J (2005) Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105:2214–2219

    Article  PubMed  CAS  Google Scholar 

  • Bruijn M de, Speck N, Peeters M, Dzierzak E (2000) Definitive hematopoietic stem cells first develop within the major arterial regions of the mouse embryo. EMBO J 19:2465–2474

    Article  PubMed  Google Scholar 

  • 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  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Deans R, Moseley A (2000) Mesenchymal stem cells: biology and potential clinical use. Exp Hematol 28:875–884

    Article  PubMed  CAS  Google Scholar 

  • Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM (2002) Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 99:3838–3843

    Article  PubMed  Google Scholar 

  • Klyushnenlova E, Mosca J, McIntosh K (1998) Human mesenchymal stem cells suppress allogeneic T cell responses in vitro: implications for allogeneic transplantation. Blood 92:642a

    Google Scholar 

  • Krampera M, Glennie S, Dyson J, Scott D, Laylor R, Simpson E, Dazzi F (2003) Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 101:3722–3729

    Article  PubMed  CAS  Google Scholar 

  • Lazarus H, Curtin P, Devine S (2000) Role of mesenchymal stem cells (MSC) in allogeneic transplantation: early phase I clinical results. Blood 392:1691

    Google Scholar 

  • Lee R, Kim B, Choi I, Kim H, Choi H, Suh K, Bae Y, Jung J (2004) Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem 14:311–324

    Article  PubMed  CAS  Google Scholar 

  • Li CD, Zhang WY, Li HL, Jiang XX (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 

  • Liechty K, MacKenzie T, Shaaban A, Radu A, Moseley A, Deans R, Marshak D, Flake A (2000) Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 6:1282–1286

    Article  PubMed  CAS  Google Scholar 

  • Macatonia S, Hosken N, Litton M, Vieira P, Hsieh C, Culpepper J, Wysocka M, Trinchieri G, Murphy K, O’Garra A (1995) Dendritic cells produce IL-12 and direct the development of Th1 cells from naive CD4+ T cells. J Immunol 154:5071–5079

    PubMed  CAS  Google Scholar 

  • Mitchell K, Weiss M, Mitchell IB (2003) Matrix cells from Wharton’s jelly form neurons and glia. Stem Cells 21:50–60

    PubMed  CAS  Google Scholar 

  • Pittenger M, Mackay A, Beck S, Jaiswal R, Douglas R, Mosca J, Moorman M, Simonetti D, Craig S, Marshak D (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Ralf H (2000) Isolation of primary and immortalized CD34− hematopoietic and mesenchymal stem cells from various sources. Stem Cells 18:1–9

    Article  Google Scholar 

  • Rao M, Mattson M (2001) Stem cells and aging: expanding the possibilities. Mech Aging Dev 122:713–734

    Article  PubMed  CAS  Google Scholar 

  • Resnik D (2002) The commercialization of human stem cells: ethical and policy issues. Health Care Anal 10:127–154

    Article  PubMed  Google Scholar 

  • Steinborn A, Gall C von, Hildenbrand R, Stutte H, Kaufmann M (1998) Identification of placental cytokine-producing cells in term and preterm labor. Obstet Gynecol 91:329–335

    Article  PubMed  CAS  Google Scholar 

  • Toma C, Pittenger M, Cahill K, Byrne B, Kessler P (2002) Human mesenchymal stem cells differentiate to a cardiomyocyte phenotype in the adult murine heart. Circulation 105:93–98

    Article  PubMed  Google Scholar 

  • Zhang Y, Li CD, Jiang XX, Li HL, Tang PH, Mao N (2004) Comparison of mesenchymal stem cells from human placenta and bone marrow. Chin Med J (Engl) 117:882–887

    CAS  Google Scholar 

  • Zhao L, Duan W, Reyes M, Keene C, Verfaillie C, Low W (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Weiyuan Zhang.

Additional information

This study was supported by a grant from the National Natural Science Foundation (no. 30571949), by the Beijing Nova Star program, by the Beijing Elitist Fund (20051D0301029), and by the Beijing Obstetrics and Gynecology Hospital.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, C., Zhang, W., Jiang, X. et al. Human-placenta-derived mesenchymal stem cells inhibit proliferation and function of allogeneic immune cells. Cell Tissue Res 330, 437–446 (2007). https://doi.org/10.1007/s00441-007-0504-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-007-0504-5

Keywords

Navigation