Mesenchymal stem cells induce expression of cD73 in human monocytes in vitro and in a swine model of myocardial infarction in vivo
The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti- inflammatory regulation by Ado. Mesenchymal stem c...
| Autores: | , , , , , |
|---|---|
| Formato: | artículo |
| Fecha de publicación: | 2017 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:196945 |
| Acesso em linha: | https://ddd.uab.cat/record/196945 https://dx.doi.org/urn:doi:10.3389/fimmu.2017.01577 |
| Access Level: | acceso abierto |
| Palavra-chave: | CD73 Adenosine Immunomodulation Mesenchymal stem cell Ectonucleotidase Myocardial infarction Purigernic signaling Regeneration |
| Resumo: | The ectoenzymes CD39 and CD73 regulate the purinergic signaling through the hydrolysis of adenosine triphosphate (ATP)/ADP to AMP and to adenosine (Ado), respectively. This shifts the pro-inflammatory milieu induced by extracellular ATP to the anti- inflammatory regulation by Ado. Mesenchymal stem cells (MSCs) have potent immunomodulatory capabilities, including monocyte modulation toward an anti-inflammatory phenotype aiding tissue repair. In vitro, we observed that human cardiac adipose tissue-derived MSCs (cATMSCs) and umbilical cord MSCs similarly polarize monocytes toward a regulatory M2 phenotype, which maintained the expression of CD39 and induced expression of CD73 in a cell contact dependent fashion, correlating with increased functional activity. In addition, the local treatment with porcine cATMSCs using an engineered bioactive graft promoted the in vivo CD73 expression on host monocytes in a swine model of myocardial infarction. Our results suggest the upregulation of ectonucleotidases on MSC-conditioned monocytes as an effective mechanism to amplify the long-lasting immunomodulatory and healing effects of MSCs delivery. |
|---|