Development of effective biomaterial-based systems for the efficient and safe delivery of iPSC-derived macrophages into the skeletal muscle to treat limb ischemia

Abstract

The main objective of the current thematic project of FAPESP is to study the relationship between the colony- stimulating factors (CSFs) and the type of monocytes/macrophages recruited under normoxia and hypoxia, and to elaborate procedures of gene and cell therapy of ischemic diseases by recruiting more proresolutive macrophages or by implanting proresolutive macrophages genetically engineered from iPSC in the ischemic muscles. In general, these cells or vectors are injected directly into the skeletal muscle for therapy; however, the transfer rate of these cells and vectors is low because of leakage and loss of biological activity due to the high initial local concentration. In addition, the leakage of vectors and cells can also contaminate other tissues, which is a very worrying biosafety issue.Our proposal is to develop biomaterial-based vector and cell delivery systems consisting of hydrogels and biocompatible microspheres, such as fibrin or poly (µ-caprolactone). This collaborative project was elaborated based on the long experience of Dr. Willerth's group in the synthesis of biomaterials and the study of their interaction with proteins and cells, and many years of experience of gene therapy for ischemic diseases by Dr. Han's group. During the exchange missions, visits to research laboratories in cognate areas and a short course on biomaterials are scheduled. (AU)