Macrophages ameliorate bone marrow inflammatory injury and promote hematopoiesis in mice following hematopoietic stem cell transplantation

Abstract

Bone marrow macrophages have been demonstrated to serve a critical role in promoting maintenance and retention of hematopoietic stem cells (HSCs). Our previous study indicated increased macrophages infiltration in bone marrow after HSC transplantation (HSCT). However, it is not well understood whether macrophages affect hematopoietic reconstitution after HSCT. The present study aimed to investigate the role of macrophages in hematopoietic reconstitution after HSCT. BALB/c mice were divided into HSCT, HSCT+Clodronate Liposomes, HSCT+PBS Liposomes, HSCT+RS102895 and HSCT+Vehicle groups and sacrificed on day 7, 14, 21, 28 and 35 after HSCT. Analysis was performed to detect the changes of bone marrow pathology by H&E staining and the number of macrophages was assessed by immunohistochemical staining and western blot analysis. The number of c-kit+ sca-1+ and c-kit+ was measured by flow cytometry. Mice with a depletion of bone marrow macrophages displayed significantly reduced overall survival, delayed hematopoietic recovery, a reduced number of hematopoietic stem/progenitor cells and bone marrow cells as well as exaggerated bone marrow injury. However, compared with the HSCT+Vehicle group, mice with an increased number of bone marrow macrophages exhibited no difference of overall survival, had accelerated hematopoietic reconstitution, a higher number of hematopoietic stem/progenitor cells and bone marrow cells and ameliorated bone marrow injury. In conclusion, the present study indicated that bone marrow macrophages serve a protective role in bone marrow injury and may promote hematopoiesis in mice after HSCT, suggesting manipulation of macrophages may be a novel strategy for improving the efficacy of HSCT.