1012 – BONE MARROW ADIPOSITY IN REGENERATIVE HEMATOPOIESIS

Abstract

In 1882 E. Neumann first noted the inverse relationship between adipogenesis and hematopoiesis within the human bone marrow. Specifically, he documented the predominance of yellow adipocytic marrow in distal bones in homeostatic conditions, and the infiltration of distal sites by red hematopoietic marrow in disorders of hematopoiesis. During the 1970's, M. Tavassoli and collaborators first presented the notion of labile and stable marrow adipocytes based on differences in fatty acid saturation as revealed by performic acid Schiff (PFAS) staining, and revealed their plasticity through seminal studies on ectopically transplanted marrow. This concept was further developed by Scheller et al. in 2016 as "regulated" and "constitutive" bone marrow adipose tissue (cBMAT and rBMAT). We are interested in studying the effect of bone marrow adipogenesis in hematopoiesis. It is now well known that red-to-yellow marrow transitions occur in all scenarios of hematopoietic insult. In fact, the inverse relationship between bone marrow adipogenesis and hematopoiesis is so predictable that human pathologists determine hematopoietic activity or "cellularity" as the ratio of hematopoietic cells to adipocytes within the bone marrow, with aplasia usually defined as a cellularity lower than 10%. Back in 2009 we concluded a net negative effect of bone marrow adipocytes in hematopoiesis both in homeostasis (mostly reflecting the effect of cBMAT) and upon stress hematopoiesis following irradiation-mediated aplasia (mostly reflecting the effect of rBMAT). Others have since validated the effect of PPARg inhibitors in accelerating hematopoietic recovery. To further dissect this phenomenon, we have developed an <i>in vitro</i> system to model the red-to-yellow-to-red marrow transition, and an image-recognition tool that allows for unbiased quantification of BM adipocytes <i>in vivo</i> (MarrowQuant Plug-In). Data compatible with the hypothesis that preadipocytes support hematopoiesis while fully mature adipocytes inhibit rapid HSC proliferation will be presented, compatible with the emerging view of adipoCARs.