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Grafting induced pluripotent stem cells-derived tenocytes contribute to recovery of motor function after Achilles tendon rupture in rat

ABSTRACT: Self-renewal of tendons is rare since the vascular formation inside is extremely poor, thus reconstructive surgery using autologous tendons has been often taken place in the case of severe injury. However, the rate of re-injury after surgery is relatively high, and collection of autologous tendons leads muscle weakness which results in prolonged rehabilitation. Here, we introduce the induced pluripotent stem cells (iPSCs)-based technology aiming at developing a new therapeutic option after tendon injury. Firstly, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in the vertebrate embryo. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSCs-derived tenocytes. We then demonstrated that grafting iPSCs-tenocytes contributed to recovery of motor function after Achilles tendon injury in rat via engraftments and paracrine effects. The biomechanical strength of regenerated tendons recovered comparable to that of healthy tendons. We propose that the iPSCs-tenocytes will provide a novel therapeutic option in tendon injury.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Mio Iwasaki

PROVIDER: PXD020887 | JPOST Repository | Thu Jul 01 00:00:00 BST 2021

REPOSITORIES: jPOST

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Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

Nakajima Taiki T Nakahata Akihiro A Yamada Naoki N Yoshizawa Keiko K Kato Tomoaki M TM Iwasaki Mio M Zhao Chengzhu C Kuroki Hiroshi H Ikeya Makoto M

Nature communications 20210818 1

Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we de ...[more]

PMID: 34408142

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Project description:BACKGROUND: Ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal Stromal Cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy, however, their full potential in treating AKI remains unknown.METHODS: In this study, we employed an in vitro model of chemically-induced ischemia using antimycin A combined with 2-deoxy-D-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards, we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential) and overall cell metabolism by metabolomics.RESULTS: Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40-50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.CONCLUSION: Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.

Dataset Information

Grafting induced pluripotent stem cells-derived tenocytes contribute to recovery of motor function after Achilles tendon rupture in rat

Publications

Grafting of iPS cell-derived tenocytes promotes motor function recovery after Achilles tendon rupture.

Similar Datasets

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