Sulfated Polysaccharide Regulates the Homing of HSPCs in a BMP-2-Triggered In Vivo Osteo-Organoid

Abstract

Hematopoietic stem cell transplantation (HSCT) is a well-established method for a variety of acquired and congenital diseases. However, the limited number and sources of therapeutic hematopoietic stem/progenitor cells (HSPCs) hinder the further application of HSCT. A BMP-2 triggered in vivo osteo-organoid that is previously reported, serves as a kind of stem cell biogenerator, for obtaining therapeutic HSPCs via activating the residual regenerative capacity of mammals using bioactive biomaterials. Here, it is demonstrated that targeting the homing signaling of HSPCs elevates the proportions and biological functions of HSPCs in the in vivo osteo-organoid. Notably, it is identified that sulfonated chito-oligosaccharide, a degradation product of sulfonated chitosan, specifically elevates the expression of endothelial protein C receptor on HSPCs and vascular cell adhesion molecule-1 on macrophages in the in vivo osteo-organoid, ultimately leading to the production of adequate therapeutic HSPCs. This in vivo osteo-organoid approach has the potential to provide an alternative HSPCs source for HSCT and benefits more patients.