Combining Immune Modification And Tissue Engineering Approaches For More Effective Stem Cell-based Therapy
Mesenchymal stromal cells, also referred to as (mesenchymal stem cells; MSCs), are ideal candidates for regenerative medicine and cellular therapeutics due to several qualities they possess. Nowadays, MSCs are the subject of extensive research to explore their best applicable potential, and pinpoint the keys these cells hold that can open doors in the area of regenerative medicine and inflammatory disease amelioration. Cellular therapy approaches utilizing MSCs face the hindrances of MSC- heterogeneity, immunogenicity due to donor variability, their different routes of delivery and migratory capacity, and the mechanisms governing their immunomodulatory properties. This research project aims at addressing the regenerative and tissue repair potential of locally administered MSCs by implementing a new technology to generate a homogeneous, safe, and “under control” MSCs from PSCs for therapeutic applications that require differentiated MSCs to persist at the site of injury. On the other hand, this research project simultaneously addresses the apoptotic MSCs metabolite release that confers therapeutic efficacy of intravenously administered MSCs despite their quick clearance after administration. Building on previous findings we aim to identify metabolites released by apoptotic MSCs that are of relevance to their therapeutic outcomes, investigate how genetic deletion of PANX-1 channel in MSCs would affect their therapeutic effects in a lung disease model (PANX1 deletion will block the metabolites released from that channel during MSC apoptosis), and in relevance we aim to investigate how the therapeutic efficacy of MSC-apoptotic bodies compare to that of intravenously administered MSCs.