Establishment and tenogenic characterization of canine tendon-derived stem cells compared with adipose-derived stem cells

Abstract

Abstract Background Tendon-derived stem cells (TDSCs) possess inherent lineage specificity for tendon regeneration. However, their characteristics in dogs remain poorly defined. Establishing a canine tendon-derived stem cell (cTDSC) population and verifying its tenogenic properties is essential for developing species-appropriate regenerative strategies. Results cTDSCs were isolated from adult canine tendons collected after completion of an unrelated IACUC-approved experiment. The cells expanded stably until passage eight while maintaining a fibroblast-like morphology. They demonstrated adipogenic, chondrogenic, and osteogenic differentiation and expressed mesenchymal markers including SRY-box transcription factor 2 (SOX2), ecto-5′-nucleotidase (CD73), and Thy-1 cell surface antigen (CD90), together with tendon-associated genes such as scleraxis ( SCX ), mohawk homeobox ( MKX ), tenascin-C ( TNC ), and tenomodulin ( TNMD ) at baseline. During tenogenic induction, cTDSCs exhibited early upregulation of SCX and MKX , followed by progressive increases in TNC , TNMD , and collagen type I ( COL1A1 ), accompanied by a decline in collagen type III ( COL3A1 ). These temporal patterns mirror the established phases of tendon maturation. Compared with canine adipose-derived stem cells (cADSCs), cTDSCs showed significantly higher expression of tendon-associated genes and proteins during induction, indicating a more pronounced tenogenic differentiation response. Collectively, these findings demonstrate that cTDSCs retain the intrinsic tendon-specific priming derived from their native microenvironment, underscoring their value as a biologically relevant progenitor cell source. Conclusions This study established cTDSCs as a tendon-specific mesenchymal stem cell population with superior tenogenic responsiveness to cADSCs. These findings provide foundational, species-specific data for future translational research on canine tendon repair and regenerative therapies.