Abstract
BACKGROUND: Taking advantage of homogeneously marked cells from green fluorescent protein (GFP) transgenic mice, we have previously demonstrated that adipose-derived stromal cells (ASCs) and bone marrow-derived stromal cells (BSCs) differentiate into a variety of cell lineages both in vitro and in vivo. In the present study, we extended this approach to regenerate bone marrow.
METHODS: ASCs isolated from the inguinal fat pads of GFP mice were cultured in vitro for five passages and seeded onto hydroxyapatites with small pores. The hydroxyapatites including ASCs were subsequently implanted into immunocompetent mice subcutaneously. Two months later, the hydroxyapatites were extirpated for histological and immunohistochemical analyses.
RESULTS: The specimens were covered with adipose tissues including extensively developed microvessels and GFP+ cells. Histological examination showed that the pores were filled with typical bone marrow composed of adipocytes, hematopoietic cells, vasculatures, and matrix. Immunohistochemical analysis confirmed that the GFP+ ASCs had differentiated into osteoblasts and vascular endothelial cells, but not hematopoietic cells.
CONCLUSION: We demonstrated for the first time that bone marrow can be regenerated from ASCs. Bone marrow regeneration from non-bone-marrow-derived cells will have a great impact on the treatment of various bone marrow-related disorders, in particular idiopathic myelofibrosis and osteopetrosis, in which there is no place for hematopoietic stem cells to survive. Furthermore, in combination with gene transfer, bone marrow regeneration may be applied to the development of novel therapeutic approaches for various kinds of hematopoietic diseases.
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