Hematopoietic Function Restoration by Transplanting Bone Marrow Niches In Vivo Engineered Using Carbonate Apatite Honeycomb Bioreactors

Abstract

Hematopoietic stem cell (HSC) transplantation is used to treat blood and immunodeficient diseases. HSC expansion techniques must be developed to prevent complications and ensure reliable therapeutic efficacy. Hence, several studies have attempted in vitro expansion of HSCs using scaffolds but failed to mimic the diverse and complex nature of HSC environments. Herein, an artificial HSC microenvironment, bone marrow (BM) niches is created, through in vivo engineering using carbonate apatite honeycomb scaffolds and the potential of these scaffolds in restoring lost hematopoietic function and immunity is investigated. BM niches are generated in every honeycomb channel, wherein HSCs are gradually aggregated. Compared to the actual BM, the scaffolds exhibit a 9.9- and 78-fold increase in the number of stored CD45⁻ CD34⁺ side scatter^low cells that are mainly considered HSCs at 8 and 12 weeks, respectively. The transplantation of the honeycomb scaffold containing HSCs and BM niches into immunocompromised mice increases peripheral blood chimerism and restores hematopoietic function and the number of immunocytes (monocytes and lymphocytes) to normal levels. This study contributes to the development of efficient HSC transplantation techniques. Additionally, in vivo-engineered integrated tissues using honeycomb scaffolds can be used to elucidate the interplay between the BM niches and resident cells.