Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation
| Autor: | D. Stecher, Dries A. M. Feyen, Henk Rozemuller, Willy A. Noort, H. J. Bühring, Martinus I. F. J. Oerlemans, Sridevi Jaksani, B. Naaijkens, Joost P.G. Sluijter, Anton C.M. Martens, P. A. F. M. Doevendans |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cellular differentiation T-Lymphocytes Sus scrofa Bone Marrow Cells Cell Separation Mice SCID immunomodulation Mesenchymal Stem Cell Transplantation Immunophenotyping Cell therapy Mice Antigen Antigens CD Osteogenesis Adipocytes Animals Humans CD90 Cell Proliferation Adipogenesis Osteoblasts biology CD271+ cells Myocardium CD44 Mesenchymal stem cell Cell Differentiation Mesenchymal Stem Cells Cell Biology Original Articles cellular therapy Flow Cytometry Transplantation pMSC myocardial infarction Phenotype Immunology Heart Function Tests biology.protein Cancer research Molecular Medicine hMSC Chondrogenesis |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune-modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible. |
| Databáze: | OpenAIRE |
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