Tendons are tissues that connect muscles to bones and are important for movement and locomotion. Tendon injuries are quite common, with millions of people – especially athletes – affected worldwide, and can often take months to recover, with a significant impact on quality of life. Additionally, although there are many treatment options, none of them are a perfect cure and many result in pain, immunogenicity, or long-term treatment failure. Therefore, a new therapeutic strategy for tendon repair is needed.
In a study published in the Journal of Tissue Engineering in January 2022, researchers at Tokyo Medical and Dental University (TMDU) succeeded in inducing human stem cells to create an artificial tendon-like tissue that mimics the properties of tendon and offers significantly improved tendon reconstruction in a mouse tendon rupture model.
Human induced pluripotent stem cells, or hiPSCs, are special stem cells that can be derived from any adult cell and can be differentiated into any specialized cell type. “By using hiPSCs with Mohawk (Mkx), we could produce artificial tendon tissue.” explains Hiroki Tsutsumi, lead author of the study. Mohawk is a transcription factor that promotes the expression of genes involved in the formation of tendons and thus leads to the differentiation of stem cells into tendon cells. These Mohawk-expressing stem cells were then placed in a specialized 3D culture system that exerts mechanical force on the cells as they grow. This simulates the conditions for tendon development and improves cell alignment and organization, allowing them to create tendon-like tissue.
Next, the research team tested the artificial tendon in a mouse model of tendon rupture. The results were exciting. Six weeks after implantation, the artificial tendon had mechanical properties similar to those of a normal, undamaged mouse tendon. Additionally, the implanted tendon-like tissue was able to recruit and mobilize host tendon cells that can further participate in the repair process. This confirmed good tissue integration.
“We have demonstrated that human induced pluripotent stem cell-derived bio-tendons have similar mechanical and biological properties to normal tendons and can be fully integrated relatively quickly after transplant surgery in a mouse model, making it a viable strategy. interesting for clinical application in the tendon. The next step towards clinical translation would be to test them in large animal models to assess their capacity as biomaterials on a larger scale”, concludes Hiroshi Asahara, lead author of the study. These promising results suggest that a new medical strategy for tendon repair may be clinically available in the future.
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Material provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.