SCAFFOLD-FREE SUSPENSION OF UNDIFFERENTIATED MESENCHYMAL STROMAL CELLS (MSCS) ARE ABLE TO REPAIR NOT FULL-THICKNESS DAMAGED TENDON IN RACE HORSES

Abstract

In view of possible clinical applications of mesenchymal stromal cells (MSCs), interesting results in repairing the Achilles tendon have been achieved in rabbit models since 1997. Histological and immunochemical studies have demonstrated the quality of repair. A basic problem in tissue repair is the way to administer stem cells. Several questions remain:

1. have the cells to be differentiated or not?

2. Could cells be administered without using scaffolds?

Attempting to cure, as a clinical model, horses with a pathological core lesion in the superficial digital flexor tendon (SDFT), MSCs were recovered from autologous bone marrow, expanded ex vivo, suspended in autologous serum and re-injected directly into the core lesion.

All 11 horses implanted with autologous MSCs exhibited no adverse reaction due to the implantation of the cells, either locally or systemically. After rehabilitation therapy nine MSC-treated animals recovered from their clinical conditions, had an excellent ultrasound image of tendons after a period ranging from 3 to 6 months, and returned to racing with good or even optimal results in the previous category of competition in 9 to 12 months without any re-injuring event. All of them are still active more than 2 years from diagnosis. One of the 2 remaining horses received less than 1×106 of MSCs, and its tendon did not heal relapsing after rehabilitation, the other was lost to follow-up. In contrast, most of horses from the control group showed tendon ultrasound images that revealed fibrosis during the healing process, and all of them were re-injured after a median time of 7 months.

The ability of tissue microenvironments to induce cell differentiation could render unnecessary a partial or total ex vivo differentiation and direct infusion of undifferentiated MSCs could represent a safe therapeutic approach to tendon repair.