Directing iPSC differentiation into iTenocytes using combined scleraxis overexpression and cyclic loading.

Return to Grants

Publication Year:
2023
Authors:
Angela Papalamprou, Victoria Yu, Angel Chen, Tina Stefanovic, Giselle Kaneda, Khosrowdad Salehi, Chloe M Castaneda, Arkadiusz Gertych, Juliane D Glaeser, Dmitriy Sheyn
PubMed ID:
36203346
Funding Grants:
Public Summary:
Tendon injuries are hard to heal because there aren’t yet effective cell-based treatments that can fully repair tendon tissue. This study looked for a better way to create tendon cells for use in regenerative therapies. Researchers started with induced pluripotent stem cell (iPSC)-derived stromal cells—a type of lab-grown cell that can turn into many different tissues—and tried to make them become tendon cells (called tenocytes). To do this, they used two key strategies: - Forcing the cells to produce Scleraxis (Scx), a gene known to control tendon formation. - Applying mechanical stretching, mimicking the pulling forces tendons experience in the body. They found that these stem cell–derived cells responded much better than traditional bone marrow–derived stem cells. The combination of Scx and stretching caused the cells to show tendon-like structure, gene activity, and protein organization—indicating successful transformation into tendon cells.
Scientific Abstract:
Regenerative therapies for tendon are falling behind other tissues due to the lack of an appropriate and potent cell therapeutic candidate. This study aimed to induce tenogenesis using stable Scleraxis (Scx) overexpression in combination with uniaxial mechanical stretch of iPSC-derived mesenchymal stromal-like cells (iMSCs). Scx is the single direct molecular regulator of tendon differentiation known to date. Bone marrow-derived (BM-)MSCs were used as reference. Scx overexpression alone resulted in significantly higher upregulation of tenogenic markers in iMSCs compared to BM-MSCs. Mechanoregulation is known to be a central element guiding tendon development and healing. Mechanical stimulation combined with Scx overexpression resulted in morphometric and cytoskeleton-related changes, upregulation of early and late tendon markers, and increased extracellular matrix deposition and alignment, and tenomodulin perinuclear localization in iMSCs. Our findings suggest that these cells can be differentiated into tenocytes and might be a better candidate for tendon cell therapy applications than BM-MSCs.