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

Abstract

Cell therapies and regenerative medicine interventions require an adequate source of therapeutic cells. Here, we demonstrate that 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 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 (CCl 4 )–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 therapeutic potentials of in vivo osteo-organoid–derived cells in cell therapies.

Organoid and organoid extracellular vesicles for osteoporotic fractures therapy: Current status and future perspectives

“…More and more bone repair composite materials, such as hydrogels, 7 targeted bone biomaterials, 8 nano‐engineered biofilms, 9 silk fibroin‐based biomaterials, 10 are becoming an important direction of bone repair. Liu et al 11 . designed BMP‐2‐initiated in vivo osteo‐organoid using active biomaterials.…”

“…More and more bone repair composite materials, such as hydrogels, 7 targeted bone biomaterials, 8 nanoengineered biofilms, 9 silk fibroin-based biomaterials, 10 are becoming an important direction of bone repair. Liu et al 11 designed BMP-2-initiated in vivo osteo-organoid using active biomaterials. The organoid is capable of forming bone marrow-like structures rich in hematopoietic stem and progenitor cells, MSCs, and a variety of immune cells.…”

A Review of Advanced Biomaterials and Cells for the Production of Bone Organoid

“…Reproduced with permission. [ 114 ] Copyright 2023, The Authors, published by American Association for the Advancement of Science.…”

“…Dai et al [ 114 ] explored the potential application of bone organoid containing BMP‐2 scaffolds for the treatment of bone defects at different developmental stages. This cell‐free strategy serves as an ecological environment for stem cells and immune cells to communicate and exchange, and can harvest abundant autologous cells for osteogenesis, fibrogenesis, and hematopoiesis (Figure 12C).…”

“…C) Implantation of gelatin sponge containing BMP-2 into the medial muscle pocket near the femur of mice to produce bone organoid. Reproduced with permission [114]. Copyright 2023, The Authors, published by American Association for the Advancement of Science.…”