Use of MSC to optimize transplantation outcome of gene edited-HSC

Mesenchymal Stromal Cells (MSC) are a fundamental component of the hematopoietic stem cells (HSC) niche where they support haematopoiesis. Moreover, MSC have been employed to promote engraftment of HSC and to stimulate their ex vivo expansion in 2D culture systems. Given the importance of HSC dose for successful engraftment of transplanted cells, the identification of strategies to optimize either the engraftment in vivo or the expansion ex-vivo of gene edited HSC is of paramount importance in view of the clinical application of gene editing. In the present project, we propose to employ different strategies which take advantage of the HSC-supportive properties of MSC to facilitate the clinical application of targeted genome editing: the co-infusion in vivo of MSC to prevent graft failure and facilitate engraftment of gene edited HSC and the ex-vivo maintenance/expansion of gene edited HSC to increase the number of edited cells available for GT. The results of these studies may turn out to be crucial for the successful clinical introduction of autologous HSC transplantation with gene edited HSC.