In a new study, researchers have successfully induced human stem cells to create artificial tendon-like tissue that mimics tendon properties and offers significantly improved tendon reconstruction in a mouse tendon-rupture model. Tendons are tissues that connect muscles to bones and are important for movement and locomotion.
Human induced pluripotent stem cells, or hiPSCs, are special stem cells that can be derived from any adult cells and can be differentiated into any specialized cell-type. “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 tendon-formation and thus drives differentiation of stem cells into tendon cells. These Mohawk-expressing stem cells were then put in a specialized 3D culture system that exerts mechanical force on the cells while they are growing. This simulates the conditions for tendon development and enhances the cell alignment and organization, allowing them to create tendon-like tissues.
Next, the research team tested the artificial tendon in a mouse model of tendon rupture. The results were exciting. Six weeks after the implantation, the artificial tendon had similar mechanical properties to a normal undamaged mouse tendon. In addition, the implanted tendon-like tissue was able to recruit and mobilize tendon cells from the host that can further participate in the repair process.
“We demonstrated that the bio-tendons derived from human induced pluripotent stem cells have similar mechanical and biological properties to normal tendons and can be fully integrated relatively quickly after a transplant surgery in a mouse model, making them an attractive strategy for clinical application in tendon injuries. The next step towards clinical translation would be to test them in large animal models to assess their capacity as a biomaterial on a larger scale,” concludes Hiroshi Asahara.
Hiroki Tsutsumi, Ryota Kurimoto, Ryo Nakamichi, Tomoki Chiba, Takahide Matsushima, Yuta Fujii, Risa Sanada, Tomomi Kato, Kana Shishido, Yuriko Sakamaki, Tsuyoshi Kimura, Akio Kishida, Hiroshi Asahara. Generation of a tendon-like tissue from human iPS cells. Journal of Tissue Engineering, 2022; 13: 204173142210740 DOI: 10.1177/20417314221074018
Tokyo Medical and Dental University. “Connecting science to medicine: Tendon-like tissue created from human stem cells: Researchers develop artificial tendons in vitro from human stem cells that could fix common tendon injuries such as Achilles tendon rupture.” ScienceDaily. ScienceDaily, 22 February 2022. <www.sciencedaily.com/releases/2022/02/220222121305.htm>.
Photo by Clem Onojeghuo