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

Abstract

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. Stem Cells Translational Medicine 2017;6:196–208

Mouse Parthenogenetic Embryonic Stem Cells with Biparental-Like Expression of Imprinted Genes Generate Cortical-Like Neurons That Integrate into the Injured Adult Cerebral Cortex

“…Mouse and human Pg‐ESCs can be differentiated in vitro and in vivo into derivatives of all germ lineages , including neural lineages . Pg‐ESCs have therefore emerged as a potent source of histocompatible cells for liver , heart , hematopoietic tissue , tendon , and the substantia nigra . Finally, Pg‐ESCs are a more accessible source with less ethical concerns than Bp blastocysts developed from sperm fertilized‐eggs.…”

­Book‐shaped decellularized tendon matrix scaffold combined with bone marrow mesenchymal stem cells‐sheets for repair of achilles tendon defect in rabbit

“…Prior studies have shown that stem cells can be differentiated into specific tissue in different inductive microenvironment, and decellularized tendon scaffolds can induce stem cells to differentiate toward tendon . TNMD and COL1A1 are important indicators for evaluating tenogenic differentiation of BMSCs . In the current study, results of qRT‐PCR and imunofluorescent analysis indicated that the DTS could induce BMSCs to differentiate toward tendon, which may result from the scaffold microenvironment.…”

“…[10][11][12][13][14] TNMD and COL1A1 are important indicators for evaluating tenogenic differentiation of BMSCs. [24][25][26][27][28] In the current study, results of qRT-PCR and imunofluorescent analysis indicated that the DTS could induce BMSCs to differentiate toward tendon, which may result from the scaffold microenvironment. Regrettably, the underlying cellular and molecular mechanisms regarding this tenogenic difference were not addressed in the current study.…”

In vitro loading models for tendon mechanobiology

“…64,71,76,77 Although high magnitude loading seems to be closely related to tendinopathy, enhanced tenogenesis of MSCs subject to 10% bi-axial loading evidenced by increased tendon-related markers tenascin-c, TNMD, COL1A1 was reported as well. 64,78 Interestingly, Huisman et al 79 compared the pro-collagen production using two loading regimes, with results indicating that rest-inserted stretching (10% strain, 0.1 Hz, followed by 10 s rest) further increased pro-collagen production as compared to continuous loading. 79 Uniaxial loading, also known as longitudinal stretching, is achieved by applying single direction uniaxial tension on the substrate containing the cultured cells.…”