CD146/MCAM defines functionality of human bone marrow stromal stem cell populations

Area of Science:

• Stem cell biology
• Regenerative medicine
• Biomaterials science

Background:

• Identifying functionally homogenous human mesenchymal stem cell (hMSC) populations is vital for effective cell therapies.
• The surface marker CD146 was investigated for its potential to subtype heterogeneous hMSCs.

Purpose of the Study:

• To evaluate the utility of CD146 as a marker for isolating distinct hMSC subpopulations.
• To compare the in vitro and in vivo characteristics of CD146-positive and CD146-negative hMSCs.

Main Methods:

• Flow cytometry and cell sorting were used to isolate hMSC-CD146(+) and hMSC-CD146(-) populations.
• High-content analysis assessed cell morphology; in vitro differentiation and in vivo bone formation assays were performed.
• In vivo and in vitro migration capabilities were investigated using transwell assays and bioluminescence imaging.

Main Results:

• Both hMSC populations demonstrated similar in vitro osteogenic and adipogenic differentiation.
• In vivo, both subtypes formed bone and bone marrow; CD146(-) cells were enriched in bone, while CD146(+) cells were enriched in bone marrow elements.
• hMSC-CD146(+) cells showed enhanced chemotaxis, wider tissue distribution, and increased migration following femoral fracture.

Conclusions:

• CD146 effectively distinguishes hMSC subpopulations with distinct functional properties.
• The CD146(+) hMSC subset exhibits superior in vivo migration and tissue distribution capabilities.
• CD146-defined hMSCs hold significant promise for clinical applications in bone tissue regeneration.