Examining the Effects of in Vitro Co-Culture of Equine Adipose-Derived Mesenchymal Stem Cells with Tendon Proper and Peritenon Cells

Tendinopathies remain the leading contributor to career-ending injuries in horses because of the complexity of tendon repair. As such, cell-based therapies like injections of adipose-derived mesenchymal stem cells (ADMSCs, or MSCs) into injured tendons are becoming increasingly popular though their long-term efficacy on a molecular and wholistic level remains contentious. Thus, we co-cultured equine MSCs with intrinsic (tendon proper) and extrinsic (peritenon) tendon cell populations to examine interactions between these cells. Gene expression for common tenogenic, perivascular, and differentiation markers was quantified at 48 and 120 hours. Additionally, cellular metabolism of proliferation was examined every 24 hours for peritenon and tendon proper cells co-cultured with MSCs. MSCs co-cultured with tendon proper or peritenon cells had altered expression profiles demonstrating trend toward tenogenic phenotype with the exception of decreases in type I collagen (COL1A1). Peritenon cells co-cultured with MSCs had a trending and significant decrease in biglycan (BGN) and CSPG4 at 48 hours and 120 hours but overall significant increases in lysyl oxidase (LOX), mohawk (MKX), and scleraxis (SCX) within 48 hours. Tendon proper cells co-cultured with MSCs also exhibited increases in LOX and SCX at 48 hours. Furthermore, cell proliferation improved overall for tendon proper cells co-cultured with MSCs. The co-culture study results suggest that adipose-derived MSCs contribute beneficially to tenogenic stimulation of peritenon or tendon proper cells.