{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:09:33Z","timestamp":1793740173312,"version":"4.6.1"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004070","name":"Khalifa University of Science, Technology and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004070","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med. Technol."],"abstract":"<jats:p>\n                    Keratinocyte stem cells (KSCs) are the principal drivers of epidermal renewal, barrier maintenance, and wound repair. Their ability to alternate between self-renewal and differentiation is orchestrated by tightly integrated extrinsic and intrinsic programs that ensure tissue stability while enabling rapid regeneration after injury. This review synthesizes current understanding of KSC homeostasis through a unified framework of three interdependent \u201cfate locks\u201d\u2014the identity switch (\u0394Np63 \u2194 Notch\/IRF6-KLF4\/GRHL3\/OVOL), the cell-cycle lock (E2F\/MYC \u2194 p21\/p27-RB), and the mechanotransduction lock (YAP\/TAZ \u2194 Hippo\/LATS). We summarize how niche-derived cues\u2014integrins\/ECM, EGFR, Wnt, Notch, Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \/CaSR, and TGF-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2014interface with intrinsic timers such as asymmetric division, DNMT1-UHRF1-mediated epigenetic memory, the DNA-damage response, proteostasis\/autophagy, and redox signaling to steer keratinocyte fate. Building on this biological foundation, we categorize current methods for isolation and xeno-free expansion of primary human keratinocytes, emphasizing advances in defined media, feeder-free substrates, and biomimetic culture surfaces. We further review 3D and organotypic models, hydrogel-based delivery systems, and the growing portfolio of keratinocyte-derived clinical products used in wound healing. Finally, we highlight emerging applications extending beyond cutaneous repair\u2014including immunomodulation, pigment restoration, ocular and mucosal regeneration, and acellular exosome-based therapeutics.\n                  <\/jats:p>","DOI":"10.3389\/fmedt.2026.1763067","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T06:49:28Z","timestamp":1770360568000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["From basic biology to engineered therapies: the keratinocyte stem cell playbook"],"prefix":"10.3389","volume":"8","author":[{"given":"Adnan","family":"Uddin","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Khalifa University of Science and Technology","place":["Abu Dhabi, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Rahmani","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Khalifa University of Science and Technology","place":["Abu Dhabi, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahim","family":"Sajini","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah","place":["Sharjah, United Arab Emirates"]},{"name":"Bioinformatics and Computational Biology Research Group, American University of Sharjah","place":["Sharjah, United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.jdermsci.2014.11.001","article-title":"Attempts to accelerate wound healing","volume":"76","author":"Kasuya","year":"2014","journal-title":"J Dermatol 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