Directing the Differentiation of Parthenogenetic Stem Cells into Tenocytes for Tissue‐Engineered Tendon Regeneration

: Uniparental parthenogenesis yields pluripotent stem cells without the political and ethical concerns surrounding the use of embryonic stem cells (ESCs) for biomedical applications. In the current study, we hypothesized that parthenogenetic stem cells (pSCs) could be directed to differentiate into tenocytes and applied for tissue-engineered tendon. We showed that pSCs displayed fundamental properties similar to those of ESCs, including pluripotency, clonogenicity, and self-renewal capacity. pSCs spontaneously differentiated into parthenogenetic mesenchymal stem cells (pMSCs), which were positive for mesenchymal stem cell surface markers and possessed osteogenic, chondrogenic, and adipogenic potential. Then, mechanical stretch was applied to improve the tenogenic differentiation of pMSCs, as indicated by the expression of tenogenic-specific markers and an increasing COL1A1:3A1 ratio. The pSC-derived tenocytes could proliferate and secrete extracellular matrix on the surface of poly(lactic-co-glycolic) acid scaffolds. Finally, engineered tendon-like tissue was successfully generated after in vivo heterotopic implantation of a tenocyte-scaffold composite. In conclusion, our experiment introduced an effective and practical strategy for applying pSCs for tendon regeneration. SIGNIFICANCE This study examined whether parthenogenetic stem cells exhibited properties similar to ESCs, including pluripotency, clonogenicity, self-renewal, and in vitro and in vivo differentiation capacity. By sequential differentiation of parthenogenetic stem cells (pSCs), parthenogenetic mesenchymal stem cells had been established and further induced through cyclic mechanical stimulation. Cell proliferation, tendon-specific marker, and extracellular matrix-enhanced constructs were assessed in vitro and in vivo. Collectively, the study's data indicated that pSCs are an attractive cell source for tissue-engineered tendon.