Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments

Area of Science:

• Orthopedics
• Regenerative Medicine
• Cell Biology

Background:

• Atrophic long bone non-union mechanisms are unclear.
• Multipotential mesenchymal stromal cells (MSCs) are crucial for bone and blood vessel formation.
• This study investigates MSCs' role in non-union tissue formation.

Purpose of the Study:

• To examine the role of multipotential mesenchymal stromal cells (MSCs) in tissue formation at atrophic long bone non-union sites.
• To compare MSCs from non-union sites with those from induced periosteum and bone marrow.
• To assess MSC differentiation potential and angiogenic influence in vitro.

Main Methods:

• Collected tissue and MSCs from non-union sites (n=20), induced periosteal (IP) membranes (n=15), and bone marrow (n=8).
• Evaluated MSC content, differentiation, and angiogenesis in vitro using flow cytometry, histology, and quantitative PCR (qPCR).

Main Results:

• Non-union MSCs exhibited comparable differentiation to bone marrow MSCs.
• Non-union tissue had more pericytes and endothelial cells, with increased, smaller blood vessels compared to IP.
• Non-union MSCs showed distinct angiogenic gene expression, unlike IP-derived MSCs which inhibited in vitro angiogenesis.

Conclusions:

• Non-union derived MSCs possess normal differentiation capacity but altered angiogenic mediation.
• Local MSCs are implicated in the immature vascular network formation at non-union sites.
• Consider MSC angiogenic support profiles for effective regenerative therapies.