{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T21:00:37Z","timestamp":1760043637145},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T00:00:00Z","timestamp":1461888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progressive liver disease is a major health issue for which no effective treatment is available, leading to cirrhosis and orthotopic liver transplantation. However, the lack of availability of donor organs and other adverse factors including rejection limit its extensive clinical application. Cell-based therapy using mesenchymal stem\/stromal cells (MSCs) may represent an attractive therapeutic option. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we used two different animal models to investigate potential therapeutic effect of DMCs transplantation in liver injury. We found that DMCs administration alleviated liver fibrosis and restored the liver function in fibrotic mice induced by CCl<jats:sub>4<\/jats:sub>. Furthermore, in an acute irradiation induced damage model, a unique population of DMCs could engraft into the liver tissue for a long period, exhibiting the phenotype of both mesenchymal cells and macrophage cells and improve the survival of mice exposed to 8 Gy lethally total-body irradiation. These discoveries provide important evidence that DMCs therapy has a beneficial effect on liver injury and provide new insight into liver injury therapy depending on the alternative cells.<\/jats:p>","DOI":"10.1038\/srep25314","type":"journal-article","created":{"date-parts":[[2016,4,29]],"date-time":"2016-04-29T10:02:17Z","timestamp":1461924137000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models"],"prefix":"10.1038","volume":"6","author":[{"given":"Li","family":"Tan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingyu","family":"Dai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dengqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunmeng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,4,29]]},"reference":[{"key":"BFsrep25314_CR1","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1136\/gutjnl-2013-306290","volume":"64","author":"WC Hsieh","year":"2015","unstructured":"Hsieh, W. C. et al. Galectin-3 regulates hepatic progenitor cell expansion during liver injury. Gut 64, 312\u2013321, doi: gutjnl-2013-306290 (2015).","journal-title":"Gut"},{"key":"BFsrep25314_CR2","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.1182\/blood-2003-05-1670","volume":"103","author":"OK Lee","year":"2004","unstructured":"Lee, O. K. et al. Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103, 1669\u20131675, doi: 10.1182\/blood-2003-05-1670 (2004).","journal-title":"Blood"},{"key":"BFsrep25314_CR3","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1002\/jcb.20241","volume":"93","author":"OK Lee","year":"2004","unstructured":"Lee, O. K. et al. Fluvastatin and lovastatin but not pravastatin induce neuroglial differentiation in human mesenchymal stem cells. J Cell Biochem 93, 917\u2013928, doi: 10.1002\/jcb.20241 (2004).","journal-title":"J Cell Biochem"},{"key":"BFsrep25314_CR4","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1002\/hep.20469","volume":"40","author":"KD Lee","year":"2004","unstructured":"Lee, K. D. et al. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology 40, 1275\u20131284, doi: 10.1002\/hep.20469 (2004).","journal-title":"Hepatology"},{"key":"BFsrep25314_CR5","doi-asserted-by":"crossref","unstructured":"Kuo, T. K. et al. Stem cell therapy for liver disease: parameters governing the success of using bone marrow mesenchymal stem cells. Gastroenterology 134, 2111-2121, 2121 e2111-2113, doi: 10.1053\/j.gastro.2008.03.015 (2008).","DOI":"10.1053\/j.gastro.2008.03.015"},{"key":"BFsrep25314_CR6","first-page":"459","volume":"10","author":"M Mohamadnejad","year":"2007","unstructured":"Mohamadnejad, M. et al. Phase 1 trial of autologous bone marrow mesenchymal stem cell transplantation in patients with decompensated liver cirrhosis. Arch Iran Med 10, 459\u2013466, doi: 008 (2007).","journal-title":"Arch Iran Med"},{"key":"BFsrep25314_CR7","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1097\/MEG.0b013e32832a1f6c","volume":"21","author":"P Kharaziha","year":"2009","unstructured":"Kharaziha, P. et al. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol 21, 1199\u20131205, doi: 10.1097\/MEG.0b013e32832a1f6c (2009).","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"BFsrep25314_CR8","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1111\/j.1440-1746.2011.07024.x","volume":"27","author":"Z Zhang","year":"2012","unstructured":"Zhang, Z. et al. Human umbilical cord mesenchymal stem cells improve liver function and ascites in decompensated liver cirrhosis patients. J Gastroenterol Hepatol 27, Suppl 2, 112\u2013120, doi: 10.1111\/j.1440-1746.2011.07024.x (2012).","journal-title":"J Gastroenterol Hepatol"},{"key":"BFsrep25314_CR9","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s12026-013-8397-8","volume":"56","author":"J Voswinkel","year":"2013","unstructured":"Voswinkel, J., Francois, S., Gorin, N. C. & Chapel, A. Gastro-intestinal autoimmunity: preclinical experiences and successful therapy of fistulizing bowel diseases and gut Graft versus host disease by mesenchymal stromal cells. Immunol Res 56, 241\u2013248, doi: 10.1007\/s12026-013-8397-8 (2013).","journal-title":"Immunol Res"},{"key":"BFsrep25314_CR10","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1007\/s00534-002-0760-4","volume":"10","author":"G Nowak","year":"2003","unstructured":"Nowak, G., Ungerstedt, J., Wernerson, A., Ungerstedt, U. & Ericzon, B. G. Hepatic cell membrane damage during cold preservation sensitizes liver grafts to rewarming injury. J Hepatobiliary Pancreat Surg 10, 200\u2013205, doi: 10.1007\/s00534-002-0760-4 (2003).","journal-title":"J Hepatobiliary Pancreat Surg"},{"key":"BFsrep25314_CR11","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.biomaterials.2011.09.038","volume":"33","author":"J Sanchez-Adams","year":"2012","unstructured":"Sanchez-Adams, J. & Athanasiou, K. A. Dermis isolated adult stem cells for cartilage tissue engineering. Biomaterials 33, 109\u2013119, doi: 10.1016\/j.biomaterials.2011.09.038 (2012).","journal-title":"Biomaterials"},{"key":"BFsrep25314_CR12","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1667\/RR3189","volume":"162","author":"C Shi","year":"2004","unstructured":"Shi, C. et al. Transplantation of dermal multipotent cells promotes survival and wound healing in rats with combined radiation and wound injury. Radiat Res 162, 56\u201363, doi: RR3189 (2004).","journal-title":"Radiat Res"},{"key":"BFsrep25314_CR13","doi-asserted-by":"publisher","first-page":"3582","DOI":"10.1016\/j.biomaterials.2014.01.008","volume":"35","author":"L Gao","year":"2014","unstructured":"Gao, L. et al. The immunosuppressive properties of non-cultured dermal-derived mesenchymal stromal cells and the control of graft-versus-host disease. Biomaterials 35, 3582\u20133588, doi: 10.1016\/j.biomaterials.2014.01.008 (2014).","journal-title":"Biomaterials"},{"key":"BFsrep25314_CR14","doi-asserted-by":"publisher","first-page":"16973","DOI":"10.1038\/srep16973","volume":"5","author":"Y Wang","year":"2015","unstructured":"Wang, Y. et al. Non-cultured dermal-derived mesenchymal cells attenuate sepsis induced by cecal ligation and puncture in mice. Sci Rep 5, 16973, doi: 10.1038\/srep16973 (2015).","journal-title":"Sci Rep"},{"key":"BFsrep25314_CR15","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1038\/nature10116","volume":"475","author":"P Huang","year":"2011","unstructured":"Huang, P. et al. Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors. Nature 475, 386\u2013389, doi: 10.1038\/nature10116 (2011).","journal-title":"Nature"},{"key":"BFsrep25314_CR16","doi-asserted-by":"crossref","unstructured":"Du, Y. et al. Human hepatocytes with drug metabolic function induced from fibroblasts by lineage reprogramming. Cell Stem Cell 14, 394\u2013403, doi: 10.1016\/j.stem.2014.01.008(2014).","DOI":"10.1016\/j.stem.2014.01.008"},{"key":"BFsrep25314_CR17","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/S0014-5793(97)00313-X","volume":"407","author":"M Okabe","year":"1997","unstructured":"Okabe, M., Ikawa, M., Kominami, K., Nakanishi, T. & Nishimune, Y. \u2018Green mice\u2019 as a source of ubiquitous green cells. FEBS Lett 407, 313\u2013319, doi: S0014-5793(97)00313-X (1997).","journal-title":"FEBS Lett"},{"key":"BFsrep25314_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.gene.2015.03.022","volume":"564","author":"Z Wang","year":"2015","unstructured":"Wang, Z. et al. Efficacy of intervertebral disc regeneration with stem cells \u2014 A systematic review and meta-analysis of animal controlled trials. Gene 564, 1\u20138, doi: 10.1016\/j.gene.2015.03.022 (2015).","journal-title":"Gene"},{"key":"BFsrep25314_CR19","doi-asserted-by":"publisher","first-page":"e101","DOI":"10.1053\/j.gastro.2007.03.110","volume":"133","author":"T Nakamura","year":"2007","unstructured":"Nakamura, T. et al. Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model. Gastroenterology 133(91\u2013107), e101, doi: S0016-5085(07)00636-1 (2007).","journal-title":"Gastroenterology"},{"key":"BFsrep25314_CR20","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/ijms17010008","volume":"17","author":"T Wang","year":"2015","unstructured":"Wang, T. et al. Cell Density-Dependent Upregulation of PDCD4 in Keratinocytes and Its Implications for Epidermal Homeostasis and Repair. International Journal of Molecular Sciences 17, 8, doi: 10.3390\/ijms17010008 (2015).","journal-title":"International Journal of Molecular Sciences"},{"key":"BFsrep25314_CR21","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.3727\/096368914X682431","volume":"24","author":"Z Chen","year":"2015","unstructured":"Chen, Z., Wang, Y. & Shi, C. Therapeutic Implications of Newly Identified Stem Cell Populations From the Skin Dermis. Cell Transplant 24, 1405\u20131422, doi: 10.3727\/096368914X682431 (2015).","journal-title":"Cell Transplant"},{"key":"BFsrep25314_CR22","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.jss.2004.04.008","volume":"121","author":"S Chunmeng","year":"2004","unstructured":"Chunmeng, S. et al. Effects of dermal multipotent cell transplantation on skin wound healing. J Surg Res 121, 13\u201319, doi: 10.1016\/j.jss.2004.04.008 (2004).","journal-title":"J Surg Res"},{"key":"BFsrep25314_CR23","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.expneurol.2009.05.025","volume":"223","author":"SK Walsh","year":"2010","unstructured":"Walsh, S. K., Gordon, T., Addas, B. M., Kemp, S. W. & Midha, R. Skin-derived precursor cells enhance peripheral nerve regeneration following chronic denervation. Exp Neurol 223, 221\u2013228, doi: 10.1016\/j.expneurol.2009.05.025 (2010).","journal-title":"Exp Neurol"},{"key":"BFsrep25314_CR24","doi-asserted-by":"publisher","first-page":"9545","DOI":"10.1523\/JNEUROSCI.1930-07.2007","volume":"27","author":"J Biernaskie","year":"2007","unstructured":"Biernaskie, J. et al. Skin-derived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury. J Neurosci 27, 9545\u20139559, doi: 27\/36\/9545 (2007).","journal-title":"J Neurosci"},{"key":"BFsrep25314_CR25","doi-asserted-by":"publisher","first-page":"648","DOI":"10.3171\/2010.2.JNS091432","volume":"113","author":"T Higashida","year":"2010","unstructured":"Higashida, T. et al. Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats. J Neurosurg 113, 648\u2013655, doi: 10.3171\/2010.2.JNS091432 (2010).","journal-title":"J Neurosurg"},{"key":"BFsrep25314_CR26","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1002\/hep.24315","volume":"53","author":"JA Thomas","year":"2011","unstructured":"Thomas, J. A. et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration and function. Hepatology 53, 2003\u20132015, doi: 10.1002\/hep.24315 (2011).","journal-title":"Hepatology"},{"key":"BFsrep25314_CR27","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/978-1-61779-468-1_15","volume":"826","author":"M Mouiseddine","year":"2012","unstructured":"Mouiseddine, M., Francois, S., Souidi, M. & Chapel, A. Intravenous human mesenchymal stem cells transplantation in NOD\/SCID mice preserve liver integrity of irradiation damage. Methods Mol Biol 826, 179\u2013188, doi: 10.1007\/978-1-61779-468-1_15 (2012).","journal-title":"Methods Mol Biol"},{"key":"BFsrep25314_CR28","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1002\/stem.1396","volume":"31","author":"J Jung","year":"2013","unstructured":"Jung, J. et al. Human placenta-derived mesenchymal stem cells promote hepatic regeneration in CCl4 -injured rat liver model via increased autophagic mechanism. Stem Cells 31, 1584\u20131596, doi: 10.1002\/stem.1396 (2013).","journal-title":"Stem Cells"},{"key":"BFsrep25314_CR29","doi-asserted-by":"publisher","first-page":"8616","DOI":"10.1038\/srep08616","volume":"5","author":"M Park","year":"2015","unstructured":"Park, M. et al. Tonsil-derived Mesenchymal Stem Cells Ameliorate CCl4\u2013induced Liver Fibrosis in Mice via Autophagy Activation. Scientific Reports 5, 8616, doi: 10.1038\/srep08616 (2015).","journal-title":"Scientific Reports"},{"key":"BFsrep25314_CR30","doi-asserted-by":"publisher","first-page":"340257","DOI":"10.1155\/2014\/340257","volume":"2014","author":"B Usunier","year":"2014","unstructured":"Usunier, B., Benderitter, M., Tamarat, R. & Chapel, A. Management of fibrosis: the mesenchymal stromal cells breakthrough. Stem Cells Int 2014, 340257, doi: 10.1155\/2014\/340257 (2014).","journal-title":"Stem Cells Int"},{"key":"BFsrep25314_CR31","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1093\/jrr\/rrv026","volume":"56","author":"YX Chen","year":"2015","unstructured":"Chen, Y. X. et al. Mesenchymal stem cell-conditioned medium prevents radiation-induced liver injury by inhibiting inflammation and protecting sinusoidal endothelial cells. J Radiat Res 56, 700\u2013708, doi: 10.1093\/jrr\/rrv026 (2015).","journal-title":"J Radiat Res"},{"key":"BFsrep25314_CR32","doi-asserted-by":"publisher","first-page":"151679","DOI":"10.1155\/2013\/151679","volume":"2013","author":"S Francois","year":"2013","unstructured":"Francois, S. et al. Human mesenchymal stem cells provide protection against radiation-induced liver injury by antioxidative process, vasculature protection, hepatocyte differentiation and trophic effects. Biomed Res Int 2013, 151679, doi: 10.1155\/2013\/151679 (2013).","journal-title":"Biomed Res Int"},{"key":"BFsrep25314_CR33","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1189\/jlb.0106015","volume":"80","author":"S Meindl","year":"2006","unstructured":"Meindl, S., Schmidt, U., Vaculik, C. & Elbe-Burger, A. Characterization, isolation and differentiation of murine skin cells expressing hematopoietic stem cell markers. J Leukoc Biol 80, 816\u2013826, doi: jlb.0106015 (2006).","journal-title":"J Leukoc Biol"},{"key":"BFsrep25314_CR34","doi-asserted-by":"crossref","unstructured":"Vaculik, C. et al. Human dermis harbors distinct mesenchymal stromal cell subsets. J Invest Dermatol 132, 563\u2013574, doi: 10.1038\/jid.2011.355(2012).","DOI":"10.1038\/jid.2011.355"},{"key":"BFsrep25314_CR35","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1002\/hep.28139","volume":"46","author":"PA Lysy","year":"2007","unstructured":"Lysy, P. A., Smets, F., Sibille, C., Najimi, M. & Sokal, E. M. Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation. Hepatology 46, 1574\u20131585, doi: 10.1002\/hep.28139 (2007).","journal-title":"Hepatology"},{"key":"BFsrep25314_CR36","doi-asserted-by":"crossref","unstructured":"Zhu, S. et al. Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature doi: 10.1038\/nature13020 (2014).","DOI":"10.1038\/nature13020"},{"key":"BFsrep25314_CR37","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1016\/j.tiv.2009.08.014","volume":"23","author":"J De Kock","year":"2009","unstructured":"De Kock, J., Vanhaecke, T., Biernaskie, J., Rogiers, V. & Snykers, S. Characterization and hepatic differentiation of skin-derived precursors from adult foreskin by sequential exposure to hepatogenic cytokines and growth factors reflecting liver development. Toxicology in Vitro 23, 1522\u20131527, doi: 10.1016\/j.tiv.2009.08.014 (2009).","journal-title":"Toxicology in Vitro"},{"key":"BFsrep25314_CR38","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.jceh.2014.03.051","volume":"4","author":"S Giri","year":"2014","unstructured":"Giri, S. & Bader, A. Shortcut Route for Generation of Functional Hepatocyte Cells from Human Skin Allogenically for Autologous Treatment of Chronic Liver Diseases. Journal of Clinical and Experimental Hepatology 4, 74\u201378, doi: 10.1016\/j.jceh.2014.03.051 (2014).","journal-title":"Journal of Clinical and Experimental Hepatology"},{"key":"BFsrep25314_CR39","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1002\/cbin.10175","volume":"37","author":"H-I Huang","year":"2013","unstructured":"Huang, H.-I., Chen, S.-K., Wang, R. Y. L., Shen, C.-R. & Cheng, Y.-C. Human foreskin fibroblast-like stromal cells can differentiate into functional hepatocytic cells. Cell Biology International 37, 1308\u20131319, doi: 10.1002\/cbin.10175 (2013).","journal-title":"Cell Biology International"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep25314","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep25314.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep25314.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:17:49Z","timestamp":1672841869000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep25314"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,29]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,7,6]]}},"alternative-id":["BFsrep25314"],"URL":"https:\/\/doi.org\/10.1038\/srep25314","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,29]]},"assertion":[{"value":"3 February 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25314"}}