{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:54:28Z","timestamp":1790038468978,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T00:00:00Z","timestamp":1510444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The New Xiangya Talent Project of the Third xiangya hospital of Central South University","award":["JY201512"],"award-info":[{"award-number":["JY201512"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Neonatal pig islet\u2010like cell clusters (NICC<\/jats:styled-content>) are an attractive source of insulin\u2010producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC<\/jats:styled-content> after their transplantation due to apoptosis resulted from islet isolation and instant blood\u2010mediated inflammatory reaction remains to be overcome.<\/jats:p><\/jats:sec>Methods<\/jats:title>EGM<\/jats:styled-content>2 medium depleted with hydrocortisone and supplemented with 50\u00a0mmol\/L isobutylmethylxanthine, 10\u00a0mmol\/L nicotinamide, and 10\u00a0mmol\/L glucose was used to culture NICC<\/jats:styled-content> at day 1, the day after isolation and changed every other day. NICC<\/jats:styled-content> cultured with EGM<\/jats:styled-content>2 or control Ham's F\u201010 medium were collected at day 7 of culture for the following assays. The viability of NICC<\/jats:styled-content> was evaluated by AO<\/jats:styled-content>\/EB<\/jats:styled-content> staining and FACS<\/jats:styled-content>. Static assay and oxygen consumption rate analysis were performed to assess the function of NICC<\/jats:styled-content>. Insulin and glucagon gene expression were measured by real\u2010time PCR<\/jats:styled-content>. Tubing loops model and TUNEL<\/jats:styled-content> assay were performed to confirm the apoptosis\u2010resistant ability of NICC<\/jats:styled-content> cultured with modified EGM<\/jats:styled-content>2 medium. Serum starvation and hypoxia treatment were used to test the tolerant capability of NICC<\/jats:styled-content> in the microenvironment of hypoxia\/nutrient deficiency in vitro. The molecules involved in apoptosis pathways in NICC<\/jats:styled-content> were analyzed by Western blotting.<\/jats:p><\/jats:sec>Results<\/jats:title>Compared with Ham's F\u201010 medium, culturing NICC<\/jats:styled-content> with EGM<\/jats:styled-content>2 medium led to increased number and viability of NICC<\/jats:styled-content> with higher stimulation index, upregulated gene expression of both insulin and glucagon, and enhanced mitochondria function. Furthermore, fewer modified EGM<\/jats:styled-content>2 medium cultured NICC<\/jats:styled-content> were found under apoptosis when evaluated in an in vitro tubing loop model of IBMIR<\/jats:styled-content>. Moreover, EGM<\/jats:styled-content>2 medium cultured NICC<\/jats:styled-content> demonstrated much less apoptotic cells under either serum starvation or hypoxia condition than their Ham's F\u201010 medium cultured counterparts. The enhanced capability of EGM<\/jats:styled-content>2 cultured NICC<\/jats:styled-content> to resist apoptosis was associated with their elevated protein levels of anti\u2010apoptotic Bcl\u20102 family member Mcl\u20101.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Culturing NICC<\/jats:styled-content> with EGM<\/jats:styled-content>2 provides a simple and effective approach not only to increase NICC<\/jats:styled-content> yield, viability, and maturation but also to enhance their resistance to apoptosis to preserve the initial graft mass for successful islet xenotransplantation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/xen.12358","type":"journal-article","created":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T03:36:40Z","timestamp":1510544200000},"source":"Crossref","is-referenced-by-count":10,"title":["Culturing with modified EGM<\/scp>2 medium enhances porcine neonatal islet\u2010like cell clusters resistance to apoptosis in islet 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