Abstract
Rotator cuff tendon injuries often lead to shoulder pain and dysfunction. Traditional treatments such as surgery and physical therapy can provide temporary relief, but it is difficult to achieve complete healing of the tendon, mainly because of the limited repair capacity of the tendon cells. Therefore, it is particularly urgent to explore new treatment methods. In vitro experiments were performed to explore the mechanism of differentiation of umbilical cord mesenchymal stem cells (UCMSCs) to tendon cells and to evaluate their potential in promoting rotator cuff injury repair. Growth factors such as CTGF, GDF-6, and GDF-7 were used to induce the differentiation of UCMSCs, and gene expression changes during the differentiation process were analyzed by single-cell sequencing. Hes1 overexpression and animal models were constructed to study its role in UCMSCs differentiation and rotator cuff injury repair. CTGF was the optimal factor for inducing the differentiation of UCMSCs into tendon cells. With increasing induction time, UCMSCs exhibited obvious tendon cell characteristics, such as changes in cell morphology and increased expression of tendon-specific proteins (MKX, SCX, and TNC). Single-cell sequencing analysis revealed key cellular subpopulations and signaling pathways during differentiation. Furthermore, overexpression of the Hes1 gene significantly promoted the differentiation of UCMSCs to tendon cells and showed its therapeutic effect in rotator cuff injury repair in an animal model. This study confirmed the potential of UCMSCs in tendon injury repair, especially the critical role of Hes1 in promoting UCMSCs differentiation and rotator cuff tendon-bone healing, which provides a theoretical basis and experimental rationale for the development of new cellular therapeutic strategies.