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. 2022 Sep 2;13:444. doi: 10.1186/s13287-022-03113-6

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© The Author(s) 2022

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 3 — Pathogenic factors affecting fitness of tendon cells and potential strategies for rejuvenation and modification of tendon cells. Left panel summarises the pathogenic factors: chemical (e.g. Botox/Antibiotics), physical exposure (deprivation/pathological loading), gene mutations and ageing. Right panel summarises possible strategies to rejuvenate and modify TDSCs via (1) CRISPR/Cas9 (2) mitochondrial transfer (3) IPSCs to TDSCs via iMSCs (4) microRNA/enzyme/recombinant proteins/growth factor inhibitors (5) paracrine factors from BMSC/ADSC (exosomes) (6) optimal physical stimulation. BMSC, bone marrow-derived stem cell. ADSC, adipose-derived stem cell. TDSC, tendon-derived stem cell. IPSC, induced pluripotent stem cell. iMSC, IPSC-derived mesenchymal stem cell