ABSTRACT
Human placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesenchymal stem cell (MSC) maintenance medium. The homogenous layer of adherent cells exhibited a typical fibroblast-like morphology, a large expansive potential, and cell cycle characteristics including a subset of quiescent cells. In vitro differentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic and chondrogenic lineages. Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was a homogeneous cell population devoid of hematopoietic cells, which uniformly expressed CD29, CD44, CD73, CD105, CD166, laminin, fibronectin and vimentin while being negative for expression of CD31, CD34, CD45 and α-smooth muscle actin. Most importantly, immuno-phenotypic analyses demonstrated that these cells expressed class I major histocompatibility complex (MHC-I), but they did not express MHC-II molecules. Additionally these cells could suppress umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli. This strongly implies that they may have potential application in allograft transplantation. Since placenta and UCB are homogeneous, the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells (HSC) from UCB to reduce the potential graft-versus-host disease (GVHD) in recipients.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Friedenstein AJ, Gorskaja JF, Kulagina NN . Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp Hematol 1976; 4:267–74.
Caplan A . Mesenchymal stem cells. J Ortho Res 1991; 9:641–50.
Williams JT, Southerland SS, Souza J, et al. Cells isolated from adult human skeletal muscle capable of differentiating into multiple mesodermal phenotypes. Am Surg 1999; 65:22–6.
Warejcka DJ, Harvey R, Taylor BJ, et al. A population of cells isolated from rat heart capable of differentiating into several mesodermal phenotypes. J Surg Res 1996; 62:233–42.
Gronthos S, Zannettino AC, Graves SE, et al. Differential cell surface expression of the STROP-1 and alkaline phosphatase antigens on discrete development stages in primary cultures of human bone cells. J Bone Miner Res 1999; 14:47–56.
Grigoriadis AE, Heersche JN, Aubin JE . Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone derived clonal cell population: effect of dexamethason. J Cell Biol 1998; 106:2139–51.
Loncar D . Ultrastructural analysis of differentiation of rat endoderm in vitro: Adipose vascular-stromal cells induce endoderm differentiation, which in turn induces differentiation of vascular-stromal cells into chondrocytes. J Submicrose Cytol Pathol 1992; 24:509–19.
Romanov YA, Svintsitskaya VA, Smirnov VN . Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-Like cells from umbilical cord. Stem cells 2003; 21:105–10.
Campagnoli C, Roberts IA, Kumar S, et al. Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood 2001; 98:2396–402.
Erices A, Conget P, Minguell JJ . Mesenchymal progenitor cells in human umbilical cord blood. Br J Haematol 2000; 109:235–42.
Mareschi K, Biasin E, Piacibello W, et al. Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood. Haematologica 2001; 86:1099–100.
Pittinger M, Mackay A, Beck S, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284:143–7.
Haynesworth SE, Baber MA, Caplan AI . Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dexamethasone and IL-1alpha. J Cell Physiol 1996; 166:585–92.
Majumdar MK, Thiede MA, Mosca JD, et al. Phenotypic and functional comparison of cultures of marrow-derived mesenchymal stem cells (MSC) and stromal cells. J Cell Physiol 1998; 176:57–66.
Blanc KL, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 2003; 31:890–6.
Le Blanc K . Immunomodulatory effects of fetal and adult mesenchymal stem cells. Cytotherapy 2003; 5:485–9.
Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lympgocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30:42–8.
Di Nicola M, Carlo-Stella C, Magni M, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99:3838–43.
He J, Zhang Y, Jiang XX, et al. Isolation and characterization of human placenta derived adherent cells and their hematopoietic growth factor expression, Zhonghua Xue Ye Xue Za Zhi 2003; 24:652–4.
Zhang Y, Li CD, Jiang X, et al. Human placenta-derived mesenchymal progenitor cells support culture expansion of long-term culture-initiating cells from cord blood CD34+ cells. Exp Hematol. 2004; 32:657–64.
Bruder SP, Jaiswal N, Haynesworth SE . Growth kinetics, selfrenewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell biochem 1997; 64:278–94.
Conget PA, Minguell JJ . Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 1999; 181:67–73.
Barry F, Boynton R, Murphy M, et al. The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells. Biochem Biophys Res Commun 2001 30; 289:519–24.
Barry FP, Boynton RE, Haynesworth S, et al. The monoclonal antibody SH-2, raised against human mesenchymal stem cells, recognizes an epitope on endoglin (CD105). Biochem Biophys Res Commun 1999; 265:134–9.
Zhang Y, Li CD, Jiang XX, et al. Comparison of mesenchymal stem cells from human placenta and bone marrow. Chin Med J (Engl). 2004; 117:882–7.
Sun SK, Guo ZK, Xiao XR, et al. Isolation of mouse marrow mesenhymal progenitors by a novel and reliable method. Stem Cells. 2003; 21:527–35.
Krampera M, Glennie S, Dyson J, et al. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide. Blood 2003; 101:3722–9. Epub 2002 Dec 27.
Maccario R, Podesta M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haema tologica 2005; 90:516–25.
Lazarus HM, Haynesworth SE, Gerson SL, et al. Ex vivo expansion and subsequent infusion of human bone marrowderived stromal progenitor cells (mesenchymal progenitor cells): implications for therapeutic use. Bone Marrow Transplant 1995; 16:557–64.
Chung NG, Jeong DC, Park SJ, et al. Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation. Int J Hematol 2004; 80:370–6.
Acknowledgements
This study was supported by a grant from National Natural Science Foundation of China (No.30271245), Hi-Tech Research and Development Program of China (863 Program) (No. 2003AA205170), National Basic Research Program of China (973 Program) (No.G1999054302), and a grant from Beijing Gynecology and Obstetrics Hospital Affiliate of Capital University of Medical Sciences.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
LI, C., ZHANG, W., LI, H. et al. Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation. Cell Res 15, 539–547 (2005). https://doi.org/10.1038/sj.cr.7290323
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1038/sj.cr.7290323
Keywords
This article is cited by
-
Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases
Journal of Nanobiotechnology (2023)
-
Hyperthermia increases HSP production in human PDMCs by stimulating ROS formation, p38 MAPK and Akt signaling, and increasing HSF1 activity
Stem Cell Research & Therapy (2022)
-
Infusion of haploidentical HSCs combined with allogenic MSCs for the treatment of ALL patients
Bone Marrow Transplantation (2022)
-
Mechanistic Insights into Factor VIII Immune Tolerance Induction via Prenatal Cell Therapy in Hemophilia A
Current Stem Cell Reports (2019)
-
Comprehensive characterization of chorionic villi-derived mesenchymal stromal cells from human placenta
Stem Cell Research & Therapy (2018)
