Effect of partial hepatectomy on in vivo engraftment after intravenous administration of human adipose tissue stromal cells in mouse.

Abstract

Their multidifferentiation potential makes human mesenchymal stem cells (hMSCs) candidates for cell-based therapeutic strategies for tissue injuries and for hematopoietic disorders by both local and systemic application. Despite their potential clinical utility in cellular and gene therapy, the fate of adipose stromal cells (ATSCs) after systemic administration is mostly unknown. In this study, we investigated the distribution of ATSCs injected intravenously and the effect of partial hepatectomy on their distribution. Adipose tissue stromal cells (hATSCs) were obtained from adipose tissues of adult human donors. Under appropriate culture conditions, hATSCs were induced to differentiate into osteocytes and adipocyte lineages. The hATSCs were marked by infection with the lacZ-adeno virus, and the distribution of injected cells was examined by X-Gal staining. Immunosuppression was achieved by the administration of cyclosporin into mice. The hATSCs were engrafted onto various tissues, including brain, thymus, heart, liver, and lung, after intravenous administration. Liver regeneration induced by partial hepatectomy enhanced the integration of hATCSCs into the liver. These results demonstrate that hATSCs have the ability to proliferate extensively in culture, and that they maintain their multilineage differentiation potential in vitro, establishing their progenitor cell nature. These cells are promising candidates for developing novel cell-based therapeutic approaches to postnatal tissue repair.