期刊
BLOOD
卷 118, 期 12, 页码 3254-3262出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-325324
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类别
资金
- Association Nouvelles Recherches Biomedicales (ANRB)
- DIM STEM POLE
- Region Ile de France
- Universite Paris
- Institut Francilien de Recherche en Nephrologie et Transplantation (IFRNT)
- Association pour la Recherche sur le Cancer (ARC) [3272]
- Ligue contre le Cancer
- Institut National du Cancer (INCA)
- ARC/INCA
- Agence Nationale de la Recherche
A major issue in immunosuppressive biotherapy is the use of mesenchymal stem cells (MSCs) that harbor regulatory capacity. However, currently used bone marrow-derived MSCs (BM-MSCs) are short-lived and cannot assure long lasting immunoregulatory function both in vitro and in vivo. Consequently, we have generated MSCs from human induced pluripotent stem (IPS-MSCs) cells that share similar properties with embryonic stem cells (ES-MSCs). Herein, we compared the immunoregulatory properties of ES/IPS-MSCs with those of BM-MSCs and showed, for the first time, that IPS-derived MSCs display remarkable inhibition of NK-cell proliferation and cytolytic function in a similar way to ES-MSCs. Both MSCs disrupt NK-cell cytolytic machinery in the same fashion that BM-MSCs, by down-regulating the expression of different activation markers and ERK1/2 signaling, leading to an impairment to form immunologic synapses with target cells and, therefore, secretion of cytotoxic granules. In addition, they are more resistant than adult BM-MSCs to preactivated NK cells. IPS-MSCs could represent an attractive alternative source of immunoregulatory cells, and their capacity to impair NK-cell cytotoxicity constitutes a complex mechanism to prevent allograft rejection. (Blood. 2011;118(12):3254-3262)
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