https://orcid.org/0000-0002-2649-661X
Key Points
BMP-2 can generate an ectopic bone marrow (BMP-eBM) microenvironment capable of housing and maintaining a functional BM niche.
In situ adipose tissue-derived CD51highCxcl12-GFP- cells are the major cell source giving origin to CAR cells in the BMP-eBM.
Ectopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of bone marrow (BM). Although bone morphogenetic protein (BMP)-2 has been reported to induce eBM formation, it remains unproven whether BMP-2 induced eBM (BMP-eBM) can provide a functional BM niche that is comparable to native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate for the first time that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM. BMP-eBM establishes an optimized microenvironment capable of supporting hematopoietic stem cells (HSCs) and CXC-chemokine-ligand-12 (CXCL12)-abundant reticular (CAR) cells, which are critical components of the BM niche. Significantly, BMP-eBM was able to restore survival in irradiated mice. Through parabiosis and cell transplantation experiments, we identified that in situ adipose tissue-derived CD51highCxcl12-GFP- cells are the principal source of CAR cells within BMP-eBM. Furthermore, BMP-eBM can be isolated and, after preconditioning, re-transplanted as an independent, functional hematopoietic organ. In conclusion, our study confirms that BMP-eBM functions effectively as a hematopoietic organ, capable of supporting and maintaining a functional BM niche. These findings underscore BMP-2 as a crucial molecule for eBM generation and suggest its potential for addressing BM-related diseases and for use as a platform for in vitro and ex vivo biomedical applications.
