Chemically-induced osteogenic cells for bone tissue engineering and disease modeling

Area of Science:

• Biotechnology
• Regenerative Medicine
• Cell Biology

Background:

• Cell reprogramming offers a method to generate specific cell types for regenerative medicine and disease modeling.
• Obtaining osteogenic cells for bone repair and studying bone diseases remains a challenge.

Purpose of the Study:

• To reprogram human fibroblasts into chemically-induced osteogenic cells (ciOG).
• To evaluate the potential of ciOG in bone repair and disease modeling.
• To investigate the influence of engineered substrates on ciOG osteogenic capacity.

Main Methods:

• Fibroblasts were treated with a chemical cocktail (RepSox, forskolin, phenamil) to induce osteogenesis via RUNX2 activation.
• Osteogenic differentiation was confirmed by mineralized nodule formation.
• Bulk and single-cell RNA sequencing characterized the ciOG population.
• In vivo studies involved ectopic bone formation in immunodeficient mice and calvarial defect repair.
• Engineered nanofiber substrates were used to assess their impact on ciOG performance.

Main Results:

• Successful reprogramming of fibroblasts into ciOG, which exhibited an osteoblast phenotype and produced mineralized nodules.
• ciOG formed mineralized tissue in vivo, unlike parental fibroblasts.
• Osteogenic reprogramming was enhanced on engineered nanofiber substrates, accelerating bone matrix formation in a calvarial defect model.
• The ciOG platform accurately recapitulated genetic bone diseases (Proteus syndrome, osteogenesis imperfecta) for drug screening.

Conclusions:

• Chemical reprogramming provides a viable method to generate osteogenic cells from fibroblasts.
• ciOG cells demonstrate potential for bone tissue engineering and in vivo bone repair.
• Engineered biomaterials can enhance the osteogenic capacity of ciOG.
• The ciOG platform serves as a valuable tool for modeling genetic bone diseases and facilitating drug discovery.