{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:33:00Z","timestamp":1787758380577,"version":"build-2784847793"},"reference-count":99,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>Somatic cell reprogramming technology can reverse fate determinations of the differentiated cells by regulating their epigenetic and gene expression programs. This reprogramming enables the acquisition of pluripotency to differentiate into mature and functional cells, which provides sufficient cells for regenerative and reproductive medicine. Significant progress has recently been made by peers and us in reprogramming somatic cells, e.g., Sertoli cells, fibroblasts, and peripheral blood mononuclear cells into functional stem cells. In this review, we systematically summarize the development and optimization of multiple core methods for cell reprogramming, including somatic cell nuclear transfer (SCNT), transcription factor-induced reprogramming, chemical reprogramming, and clustered regularly interspaced short palindromic repeats (CRISPR)\/CRISPR-associated protein (CRISPR\/Cas)-based reprogramming. We also address the epigenetic remodeling mechanisms that are involved in somatic cell reprogramming, including the dynamic processes of chromatin accessibility regulation, DNA demethylation, histone modifications, and the regulation of non-coding RNAs (ncRNAs). Moreover, we discuss current challenges and perspectives in this field. Significantly, stem cells derived from somatic cells have great applications in regenerative medicine for treating various kinds of diseases, such as infertility, diabetes, neurodegenerative diseases, and chimeric antigen receptor T-cell (CAR-T) immunotherapy with attention to cell maturity, heterogeneity, and safety. Our in-depth understanding of approaches, mechanisms, and applications of somatic cell reprogramming into stem cells is essential for cell therapy and tissue engineering.<\/jats:p>","DOI":"10.4103\/aja20268","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:03:20Z","timestamp":1780679000000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Somatic cell reprogramming into stem cells: approaches, mechanisms, and therapeutic applications"],"prefix":"10.4103","author":[{"given":"Zhuo-Er","family":"Liao","sequence":"first","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University School of Basic Medicine, Changsha 410013, China"},{"name":"NHC Key Laboratory of Tropical Disease Control, Key Laboratory of Reproductive Health Diseases Research and Translation of Ministry of Education, Hainan Academy of Medical Sciences, Hainan Medical University School of Life Sciences and Medical Technology, Haikou 570102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"R1-20260605","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0012-1606(62)90004-0","article-title":"The transplantation of nuclei between two species of 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