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.

The Role of Osteomacs in Regulating Stem Cell Function and the Hematopoietic Niche

“…On the other hand, BM Mφ are found in the bone marrow cavity among other hematopoietic cells; and are similarly characterized as CD45+F4/80+ cells. Some subsets of macrophages have also been implicated in promoting erythropoiesis, HSC mobilization and HSC engraftment (Winkler, Sims et al 2010, Chow, Lucas et al 2011, Hoggatt and Pelus 2011, Ludin, Itkin et al 2012, Chow, Huggins et al 2013, Chang, Sengupta et al 2014, Heazlewood, Oteiza et al 2014, Jacobsen, Forristal et al 2014, Dutta, Hoyer et al 2015, Jacobsen, Perkins et al 2015, McCabe, Zhang et al 2015, Hur, Choi et al 2016, Qiao, Liu et al 2018…”

Role of ex vivo Expanded Mesenchymal Stromal Cells in Determining Hematopoietic Stem Cell Transplantation Outcome

“…Experimental depletion of monocytes and macrophages led to a decrease in BM CXCL12 and a selective inhibition of HSC maintenance genes, which caused HSC egression into the peripheral circulation (Chow et al, 2011). In the context of HSCT, macrophages are believed to perform a significant supportive role to guarantee reconstitution, although the mechanisms involved are still unclear (Qiao et al, 2018). Activation of BM macrophages following allogenic HSCT has been observed to impair correct recovery, increase mortality and lower overall survival, suggesting macrophages' critical impact (Takagi et al, 2009).…”

Revisión literaria sobre el trasplante de células madre hematopoyéticas, opciones para mejorar la asimilación y su impacto en la supervivencia de los pacientes

“…Al hacer el estudio para el trasplante es muy importante tener en cuenta que el antígeno leucocitario humano (HLA) de donadores hermanos idénticos están disponibles para el 25% de los pacientes por lo que conlleva a dificultades para realizar el procedimiento, por eso se han venido desarrollando diferentes alternativas ya mencionadas anteriormente para ampliar la posibilidad de realizar trasplante a toda persona que lo necesite [18]. Entonces para poder realizar el injerto de células madre hematopoyéticas se depende en gran medida del ambiente de la médula ósea debido a que ésta es altamente especializada, luego al in-teractuar con los receptores correspondientes en las células madre hematopoyéticas, todos los factores expresados en las células de soporte de éstas, ayudan a regular la proliferación, autorregulación y diferenciación de las células madre hematopoyéticas; dentro de los factores de soporte se encuentran los lipocitos, células endoteliales, reticulocitos y osteoblastos [24].…”