Adult Stem Cells for Musculoskeletal Tissue Regeneration

Abstract

Adult mesenchymal stem cells (MSC) have been cited to have immunoregulatory effects in addition to their regenerative and multipotency capabilities, meaning they contribute to a regenerative environment that can help repair injuries in vivo and secrete bioactive macromolecules that regulate the immune response after injury. MSCs’ abilities include regulating inflammation, apoptosis, and angiogenesis by affecting immune cell lineages.

A subset of MSCs of perivascular niche origin are characterized by the presence of the CD146 surface antigen. These CD146+ MSCs possess greater differential capabilities and immunoregulatory potential. This research compares the effectiveness of bone marrow (BM) MSCs and fat pad (FP) MSCs in responding to an inflammatory environment as well as pericytic MSCs compared to other MSCs.

For each subset of stem cells tested, the inflammatory and growth factor profile was quantified in basal, non-inflammatory, conditions and after exposure to an inflammatory environment induced by human inflammatory cytokines TNFα and IFNγ. RT-PCR for the GAPDH, CD146, IL-6, IL-8, and IDO genes and ELISA human growth factor and inflammation antibody arrays were used to quantify changes in response to inflammation.

Qualitative comparison of quantitative results suggests that CD146+ FP MSCs are the most effective subset of MSCs at responding to inflammation in vitro. As a result, CD146+ FP MSCs are the best stem cell subset to use for the millions of musculoskeletal injury treatments each year in order to regenerate injured tissue to shorten the healing process as well as prevent prolonged inflammation, scarring, and chronic tissue damage at injury sites.