A BMP-2-triggered in vivo osteo-organoid for cell therapy

Cell therapies and regenerative medicine interventions require an adequate source of therapeutic cells. Here, we demonstrate that constructing in vivo osteoorganoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells including hematopoietic stem/progenitor cells (HSPCs), mesenchymal stem cells (MSCs), lymphocytes, and myeloid cells. Profiling of the in vivo osteo-organoid maturation process delineated three stages-fibroproliferation, osteochondral differentiation, and marrow generation-each of which entailed obvious changes in the organoid structure and cell type distribution. The MSCs harvested from the osteochondral differentiation stage mitigated carbon tetrachloride (CCl4)-induced chronic liver fibrosis in mice, while HSPCs and immune cells harvested during the marrow generation stage rapidly and effectively reconstituted the impaired peripheral and solid immune organs of irradiated mice. These findings demonstrate the therapeu-tic potentials of in vivo osteo-organoid-derived cells in cell therapies.

Automated summary

Constructing in vivo osteo-organoids by implanting bone morphogenetic protein-2-loaded scaffolds into the internal muscle pocket near the femur of mice supports the growth and subsequent harvest of therapeutically useful cells, and these cells demonstrate therapeutic potentials in cell therapies such as mitigating chronic liver fibrosis and reconstituting impaired immune organs.