Hypoxia‐inducible factor 1 α (HIF1α), a regulator of metabolic change, is required for the survival and differentiation potential of mesenchymal stem/stromal cells (MSC). Its role in MSC immunoregulatory activity, however, has not been completely elucidated. In the present study, we evaluate the role of HIF1α on MSC immunosuppressive potential. We show that HIF1α silencing in MSC decreases their inhibitory potential on Th1 and Th17 cell generation and limits their capacity to generate regulatory T cells. This reduced immunosuppressive potential of MSC is associated with a metabolic switch from glycolysis to OXPHOS and a reduced capacity to express or produce some immunosuppressive mediators including Intercellular Adhesion Molecule (ICAM), IL‐6, and nitric oxide (NO). Moreover, using the Delayed‐Type Hypersensitivity murine model (DTH), we confirm, in vivo, the critical role of HIF1α on MSC immunosuppressive effect. Indeed, we show that HIF1α silencing impairs MSC capacity to reduce inflammation and inhibit the generation of pro‐inflammatory T cells. This study reveals the pivotal role of HIF1α on MSC immunosuppressive activity through the regulation of their metabolic status and identifies HIF1α as a novel mediator of MSC immunotherapeutic potential.
MARDONES, R; MARTÍNEZ, R.; PAREDES, M. J. & ZALAQUETT, E. Chondrogenic differentiation of bone marrow mesenchymal stem cells. First successful Latin-American report. Int. J. Morphol., 28(3):749-754, 2010.
SUMMARY:Osteoarthritis is the more frequent cause of disability in adult people and it is associated to cartilage degeneration of affected joints. This cartilage has a limited ability to repair. Several treatments have been tested including the use of Mesenchymal Stem Cells. These cells are an attractive source for cartilage repair because of their availability to chodrogenic differentiation by progressing sequentially through the expression of cartilage specific extracelullar matrix molecules, as in the embryologic human development. The aim is to obtain, culture and differentiate rabbit Bone Marrow derived Mesenchymal Stem Cells in vitro to chondral lineage. By differential centrifugation the mononuclear cell level was obtained from rabbit bone marrow samples. This level was cultured until 70% confluence. Chondrogenic differentiation was performed in an aggregate culture system with TGF-b1. Sample quantity, culture efficiency, confluence time of cultures and differentiation quality were all evaluated. An average sample of 14.5 ml per side was obtained, culture efficiency was 80%, and average confluence time (70%) was 18 days. Differentiation culture had an 80% efficiency and optimal differentiation quality. Rabbit Bone Marrow derived Mesenchymal Stem Cells culture is a reproducible technique and by the use of an adequate methodology chondrogenic cells can be obtained in vitro. This model permits the study of chondral differentiation process and could have direct clinical application. This is the first successful Latin-American report in Mesenchymal Stem Cells culture and chondrogenic differentiation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.