Induction of in Vivo Ectopic Hematopoiesis by a Three-Dimensional Structured Extracellular Matrix Derived from Decellularized Cancellous Bone

An in vitro blood production system could be an alternative to blood donation. We constructed a hematopoietic microenvironment using decellularized cancellous bones (DCBs) as scaffolds to sustain hematopoietic stem cells and supporting cells. The subcutaneous implantation of DCBs into mice with or without human mesenchymal stem cells (hMSCs) revealed that regardless of the presence of hMSCs DCBs were recellularized by some host cells and induced hematopoiesis. The ability of DCB to promote hematopoiesis was investigated by focusing on the components and the structure of cancellous bone, specifically reticular and adipose tissues and trabecular bone. Two decellularization methods were used to prepare DCBs. The DCBs differed concerning reticular tissue and adipose tissue. DCBs with these tissues could be recellularized at the original cellular location. An implantation experiment with DCBs revealed that they were very favorable for the persistent homing of hematopoietic stem cells. In addition, DCBs promoted ectopic hematopoiesis. The findings indicate that reticular tissues are important in directing hematopoiesis of DCBs.