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

Papalamprou, Angela; Yu, Victoria; Chen, Angel; Stefanovic, Tina; Kaneda, Giselle; Salehi, Khosrowdad; Castaneda, Chloe M.; Gertych, Arkadiusz; Glaeser, Juliane D.; Sheyn, Dmitriy

Affiliations

¹Orthopaedic Stem Cell Research Laboratory, Cedars‐Sinai Medical Center, Los Angeles, California, USA

²Board of Governors Regenerative Medicine Institute, Cedars‐Sinai Medical Center, Los Angeles, California, USA

³Department of Biomedical Sciences, Cedars‐Sinai Medical Center, Los Angeles, California, USA

⁴Department of Surgery, Cedars‐Sinai Medical Center, Los Angeles, California, USA

⁵Department of Pathology and Laboratory Medicine, Cedars‐Sinai Medical Center, Los Angeles, California, USA

⁶Department of Orthopedics, Cedars‐Sinai Medical Center, Los Angeles, California, USA

Abstract and keywords

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.

Keywords: stem cells; tendon; tissue engineering

Links

DOI: 10.1002/jor.25459

PubMed: 36203346

WoS: 000871981800001

History

Received: 2022-03-21

Revised: 2022-09-08

Accepted: 2022-09-22

Cited Works (2)

Year	Entry
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