Transcriptomic and functional comparison of adipose-and bone marrow-derived mesenchymal stem cells for tendon...

Tendons are specialized connective tissues with limited intrinsic healing properties due to hypovascularity and low metabolic activity. Mesenchymal stem cells (MSCs) possess regenerative potential for tendon injuries. Among the diverse sources of MSCs, those derived from the bone marrow (BM-MSCs) and adipose tissue (AD-MSCs) are the leading candidates. However, their relative efficacy remains underexplored, particularly in terms of biological characteristics and tenogenic differentiation. In addition, the signaling pathways driving tenogenic differentiation processes remain poorly understood. This study aimed to comprehensively investigate the regenerative potential of AD-MSCs and BM-MSCs for tendon repair.

AD- and BM-MSCs were isolated from rats and evaluated for stemness based on morphology, viability, immunophenotyping, and tri-lineage differentiation. RNA sequencing was performed to obtain a baseline molecular profile of each MSC type prior to tenogenic differentiation. We evaluated the potential of AD- and BM-MSCs to differentiate into tendon-like cells in vitro using gene expression and immunofluorescence. A rat model of Achilles tendon injury was created to evaluate the regenerative efficacy following each MSC-type injection. After 6 weeks, tendon regeneration was assessed using histological and immunohistochemical analyses.

Both MSCs displayed similarities in morphology, immunophenotyping, and tri-lineage differentiation capacity. AD-MSCs exhibited a superior proliferation rate and tenogenic differentiation compared with BM-MSCs in vitro. Transcriptomic profiling revealed that AD-MSCs significantly upregulated genes related to extracellular matrix remodeling (COL1, TN-C), immunoregulation (IL-33), and tenogenic signaling (FGF18, TGF-β1). AD-MSCs were also enriched in the PI3K-Akt signaling, MAPK signaling, and focal adhesion pathways, indicating enhanced regenerative and tenogenic potential compared to BM-MSCs. Moreover, our data show that AD-MSCs were more effective than BM-MSCs in improving collagen organization and COL1 expression in an animal model of tendon injury.

Our findings not only highlight the superior regenerative potential of AD-MSCs for tendon repair but also provide a basis for future mechanistic and therapeutic advancements in regenerative medicine.