Combined effect of ligament stem cells and umbilical-cord-blood-derived CD34+ cells on ligament healing

Transplantation of ligament-tissue-derived stem cells has become a promising approach in the repair of injured ligament. Neovascularization plays an important role in ligament healing and remodeling. Recently, human umbilical-cord-blood-derived CD34+ cells have been reported to contribute to neoangiogenesis. Therefore, we performed a series of experiments to test our hypothesis that the combination of medial collateral ligament stem cells (MCL-SCs) and umbilical-cord-blood-derived CD34+ cells has synergistic effects on tendon healing. MCL-SCs and umbilical-cord-blood-derived CD34+ cells were isolated and cultured. Rat MCL injury was treated by MCL-SCs and/or CD34+ cells. Response to the cell therapy was assessed by gross observation, histological evaluation and biomechanical testing at 2 and 4 weeks after each treatment. Although each cell therapy group induced macroscopic and morphological recovery in healing MCLs, the combined use of MCL-SCs/CD34+ cells led to further improvement in healing quality. Capillary density was significantly higher in the CD34+ cell transplantation groups than in the other groups at week 2. Biomechanical testing demonstrated that the failure load of the healing ligament was greatest in the combination therapy group. The combination of MCL-SCs and CD34+ cells as a cell therapeutic thus enhances healing and restores biomechanical function toward normal after MCL injury. The findings obtained in our study suggest that the combination of MCL-SCs and CD34+ cells transplantation represents a promising strategy for ligament injury.