{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:56:46Z","timestamp":1760101006067},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"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>Macrodactyly is a congenital disease characterized by aggressive overgrowth of adipose tissue in digits or limbs frequently accompanied with hyperostosis and nerve enlargement; its pathological mechanism is poorly understood. Adipose-derived stem cells (ASCs) have been extensively studied in tissue engineering and regenerative medicine as an ideal alternative substitute for bone marrow-derived mesenchymal stem cells (BM-MSCs), but their pathological role is largely unknown. In this study, ASCs from macrodactyly adipose tissues (Mac-ASCs) were isolated and compared to ASCs derived from the normal abdominal subcutaneous adipose tissue (Sat-ASCs) for cell morphology, surface marker expression, proliferation rate, and tri-lineage differentiation potential. Despite similar cell morphology and cell surface marker expression, Mac-ASCs showed higher cell proportion in the S phase and increased proliferation compared with Sat-ASCs. Moreover, osteogenic and chondrogenic differentiation capacities were enhanced in Mac-ASCs, with reduced adipogenic potential. In addition, the expression levels of adipogenic genes were lower in undifferentiated Mac-ASCs than in Sat-ASCs. These findings unraveled enhanced proliferation activity, a regression in the differentiation stage, and greater potentiality of ASCs in macrodactyly, which could contribute to hyperostosis and nerve enlargement in addition to adipose tissue overgrowth in patients.<\/jats:p>","DOI":"10.1038\/s41598-017-11666-3","type":"journal-article","created":{"date-parts":[[2017,9,5]],"date-time":"2017-09-05T09:30:05Z","timestamp":1504603805000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Altered Adipose-Derived Stem Cell Characteristics in Macrodactyly"],"prefix":"10.1038","volume":"7","author":[{"given":"Xi","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengbo","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Ni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,9,11]]},"reference":[{"key":"11666_CR1","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1016\/j.jhsa.2015.04.017","volume":"40","author":"JS Gluck","year":"2015","unstructured":"Gluck, J. S. & Ezaki, M. Surgical Treatment of Macrodactyly. The Journal of hand surgery \n                           40, 1461\u20131468, doi:https:\/\/doi.org\/10.1016\/j.jhsa.2015.04.017 (2015).","journal-title":"The Journal of hand surgery"},{"key":"11666_CR2","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.2106\/00004623-196749070-00001","volume":"49","author":"AJ Barsky","year":"1967","unstructured":"Barsky, A. J. Macrodactyly. The Journal of bone and joint surgery. American volume \n                           49, 1255\u20131266 (1967).","journal-title":"The Journal of bone and joint surgery. American volume"},{"key":"11666_CR3","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1097\/00006534-196706000-00008","volume":"39","author":"K Tsuge","year":"1967","unstructured":"Tsuge, K. Treatment of macrodactyly. Plastic and reconstructive surgery \n                           39, 590\u2013599 (1967).","journal-title":"Plastic and reconstructive surgery"},{"key":"11666_CR4","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/ajmg.a.36836","volume":"167","author":"KM Keppler-Noreuil","year":"2015","unstructured":"Keppler-Noreuil, K. M. et al. PIK3CA-related overgrowth spectrum (PROS): Diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. American Journal of Medical Genetics Part A \n                           167, 287\u2013295, doi:https:\/\/doi.org\/10.1002\/ajmg.a.36836 (2015).","journal-title":"American Journal of Medical Genetics Part A"},{"key":"11666_CR5","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1002\/stem.1076","volume":"30","author":"H Mizuno","year":"2012","unstructured":"Mizuno, H., Tobita, M. & Uysal, A. C. Concise review: Adipose-derived stem cells as a novel tool for future regenerative medicine. Stem cells (Dayton, Ohio) \n                           30, 804\u2013810, doi:https:\/\/doi.org\/10.1002\/stem.1076 (2012).","journal-title":"Stem cells (Dayton, Ohio)"},{"key":"11666_CR6","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1089\/107632701300062859","volume":"7","author":"PA Zuk","year":"2001","unstructured":"Zuk, P. A. et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue engineering \n                           7, 211\u2013228, doi:https:\/\/doi.org\/10.1089\/107632701300062859 (2001).","journal-title":"Tissue engineering"},{"key":"11666_CR7","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1002\/jcp.1138","volume":"189","author":"S Gronthos","year":"2001","unstructured":"Gronthos, S. et al. Surface protein characterization of human adipose tissue-derived stromal cells. Journal of cellular physiology \n                           189, 54\u201363, doi:https:\/\/doi.org\/10.1002\/jcp.1138 (2001).","journal-title":"Journal of cellular physiology"},{"key":"11666_CR8","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1091\/mbc.E09-07-0589","volume":"21","author":"PA Zuk","year":"2010","unstructured":"Zuk, P. A. The adipose-derived stem cell: looking back and looking ahead. Molecular biology of the cell \n                           21, 1783\u20131787, doi:https:\/\/doi.org\/10.1091\/mbc.E09-07-0589 (2010).","journal-title":"Molecular biology of the cell"},{"key":"11666_CR9","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2174\/1876893800901010054","volume":"1","author":"JR Maddox","year":"2009","unstructured":"Maddox, J. R., Liao, X., Li, F. & Niyibizi, C. Effects of Culturing on the Stability of the Putative Murine Adipose Derived Stem Cells Markers. The open stem cell journal \n                           1, 54\u201361, doi:https:\/\/doi.org\/10.2174\/1876893800901010054 (2009).","journal-title":"The open stem cell journal"},{"key":"11666_CR10","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-015-1405-8","volume":"16","author":"AL Basse","year":"2015","unstructured":"Basse, A. L. et al. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling. BMC genomics \n                           16, 215, doi:https:\/\/doi.org\/10.1186\/s12864-015-1405-8 (2015).","journal-title":"BMC genomics"},{"key":"11666_CR11","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.phymed.2015.12.004","volume":"23","author":"N Rahman","year":"2016","unstructured":"Rahman, N., Jeon, M., Song, H. Y. & Kim, Y. S. Cryptotanshinone, a compound of Salvia miltiorrhiza inhibits pre-adipocytes differentiation by regulation of adipogenesis-related genes expression via STAT3 signaling. Phytomedicine: international journal of phytotherapy and phytopharmacology \n                           23, 58\u201367, doi:https:\/\/doi.org\/10.1016\/j.phymed.2015.12.004 (2016).","journal-title":"Phytomedicine: international journal of phytotherapy and phytopharmacology"},{"key":"11666_CR12","doi-asserted-by":"publisher","unstructured":"Moseti, D., Regassa, A. & Kim, W. K. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules. International journal of molecular sciences \n                           17, doi:https:\/\/doi.org\/10.3390\/ijms17010124 (2016).","DOI":"10.3390\/ijms17010124"},{"key":"11666_CR13","doi-asserted-by":"publisher","first-page":"288","DOI":"10.3109\/03008207.2015.1023433","volume":"56","author":"W Wang","year":"2015","unstructured":"Wang, W. et al. Induction of transient tenogenic phenotype of high-density cultured human dermal fibroblasts. Connective tissue research \n                           56, 288\u2013299, doi:https:\/\/doi.org\/10.3109\/03008207.2015.1023433 (2015).","journal-title":"Connective tissue research"},{"key":"11666_CR14","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1097\/SAP.0b013e3181723bbe","volume":"60","author":"BM Schipper","year":"2008","unstructured":"Schipper, B. M., Marra, K. G., Zhang, W., Donnenberg, A. D. & Rubin, J. P. Regional anatomic and age effects on cell function of human adipose-derived stem cells. Annals of plastic surgery \n                           60, 538\u2013544, doi:https:\/\/doi.org\/10.1097\/SAP.0b013e3181723bbe (2008).","journal-title":"Annals of plastic surgery"},{"key":"11666_CR15","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s00441-007-0555-7","volume":"332","author":"WJ Jurgens","year":"2008","unstructured":"Jurgens, W. J. et al. Effect of tissue-harvesting site on yield of stem cells derived from adipose tissue: implications for cell-based therapies. Cell and tissue research \n                           332, 415\u2013426, doi:https:\/\/doi.org\/10.1007\/s00441-007-0555-7 (2008).","journal-title":"Cell and tissue research"},{"key":"11666_CR16","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1093\/hmg\/dds440","volume":"22","author":"JJ Rios","year":"2013","unstructured":"Rios, J. J. et al. Somatic gain-of-function mutations in PIK3CA in patients with macrodactyly. Human molecular genetics \n                           22, 444\u2013451, doi:https:\/\/doi.org\/10.1093\/hmg\/dds440 (2013).","journal-title":"Human molecular genetics"},{"key":"11666_CR17","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/ng.2332","volume":"44","author":"MJ Lindhurst","year":"2012","unstructured":"Lindhurst, M. J. et al. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nature genetics \n                           44, 928\u2013933, doi:https:\/\/doi.org\/10.1038\/ng.2332 (2012).","journal-title":"Nature genetics"},{"key":"11666_CR18","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1158\/1535-7163.MCT-06-0555","volume":"6","author":"J Wang","year":"2007","unstructured":"Wang, J. et al. Colon carcinoma cells harboring PIK3CA mutations display resistance to growth factor deprivation induced apoptosis. Molecular cancer therapeutics \n                           6, 1143\u20131150, doi:https:\/\/doi.org\/10.1158\/1535-7163.mct-06-0555 (2007).","journal-title":"Molecular cancer therapeutics"},{"key":"11666_CR19","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/nrc839","volume":"2","author":"I Vivanco","year":"2002","unstructured":"Vivanco, I. & Sawyers, C. L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nature reviews. Cancer \n                           2, 489\u2013501, doi:https:\/\/doi.org\/10.1038\/nrc839 (2002).","journal-title":"Nature reviews. Cancer"},{"key":"11666_CR20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1038\/nature14669","volume":"525","author":"S Koren","year":"2015","unstructured":"Koren, S. et al. PIK3CA(H1047R) induces multipotency and multi-lineage mammary tumours. Nature \n                           525, 114\u2013118, doi:https:\/\/doi.org\/10.1038\/nature14669 (2015).","journal-title":"Nature"},{"key":"11666_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/scrt470","volume":"5","author":"DN Silva","year":"2014","unstructured":"Silva, D. N. et al. Intramyocardial transplantation of cardiac mesenchymal stem cells reduces myocarditis in a model of chronic Chagas disease cardiomyopathy. Stem cell research & therapy \n                           5, 81, doi:https:\/\/doi.org\/10.1186\/scrt470 (2014).","journal-title":"Stem cell research & therapy"},{"key":"11666_CR22","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1055\/s-2003-40772","volume":"35","author":"M Becker","year":"2003","unstructured":"Becker, M., Ingianni, G., Lassner, F., Atkins, D. & Schroder, J. M. [Intraoperative histological sections in obstetric brachial plexus lesions\u2013comparison of macroscopic appearance, HE staining and toluidine blue staining]. Handchirurgie, Mikrochirurgie, plastische Chirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse \n                           35, 112\u2013116, doi:https:\/\/doi.org\/10.1055\/s-2003-40772 (2003).","journal-title":"Handchirurgie, Mikrochirurgie, plastische Chirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse"},{"key":"11666_CR23","doi-asserted-by":"publisher","first-page":"4279","DOI":"10.1091\/mbc.E02-02-0105","volume":"13","author":"PA Zuk","year":"2002","unstructured":"Zuk, P. A. et al. Human adipose tissue is a source of multipotent stem cells. Molecular biology of the cell \n                           13, 4279\u20134295, doi:https:\/\/doi.org\/10.1091\/mbc.E02-02-0105 (2002).","journal-title":"Molecular biology of the cell"},{"key":"11666_CR24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2223","volume":"3","author":"M Kuka","year":"2012","unstructured":"Kuka, M., Munitic, I. & Ashwell, J. D. Identification and characterization of polyclonal alphabeta-T cells with dendritic cell properties. Nature communications \n                           3, 1223, doi:https:\/\/doi.org\/10.1038\/ncomms2223 (2012).","journal-title":"Nature communications"},{"key":"11666_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0219-6","volume":"6","author":"G Chen","year":"2015","unstructured":"Chen, G. et al. Comparison of biological characteristics of mesenchymal stem cells derived from maternal-origin placenta and Wharton\u2019s jelly. Stem cell research & therapy \n                           6, 228, doi:https:\/\/doi.org\/10.1186\/s13287-015-0219-6 (2015).","journal-title":"Stem cell research & therapy"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11666-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11666-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11666-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T10:34:31Z","timestamp":1671791671000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-11666-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,11]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["11666"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-11666-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,11]]},"assertion":[{"value":"30 March 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"11090"}}