{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T07:45:45Z","timestamp":1779349545718,"version":"3.51.4"},"reference-count":17,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Our commentary is focused on three studies that used microRNA overexpression methods for directed differentiation of stem cells into insulin-producing cells. Islet transplantation is the only cell-based therapy used to treat type 1 diabetes mellitus. However, due to the scarcity of cadaveric donors and limited availability of good quality and quantity of islets for transplant, alternate sources of insulin-producing cells are being studied and used by researchers. This commentary provides an overview of distinct studies focused on manipulating microRNA expression to optimize differentiation of embryonic stem cells or induced pluripotent stem cells into insulin-producing cells. These studies have used different approaches to overexpress microRNAs that are highly abundant in human islets (such as miR-375 and miR-7) in their differentiation protocol to achieve better differentiation into functional islet beta (\u03b2)-cells.<\/jats:p>","DOI":"10.1515\/med-2020-0170","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T07:21:15Z","timestamp":1594020075000},"page":"567-570","source":"Crossref","is-referenced-by-count":4,"title":["Directed differentiation into insulin-producing cells using microRNA manipulation"],"prefix":"10.1515","volume":"15","author":[{"given":"Michael D.","family":"Williams","sequence":"first","affiliation":[{"name":"Diabetes and Islet biology Group, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney , Level 6, Medical Foundation Building, 92-94 Parramatta Road , Camperdown , NSW 2050 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mugdha V.","family":"Joglekar","sequence":"additional","affiliation":[{"name":"Diabetes and Islet biology Group, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney , Level 6, Medical Foundation Building, 92-94 Parramatta Road , Camperdown , NSW 2050 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anandwardhan A.","family":"Hardikar","sequence":"additional","affiliation":[{"name":"Diabetes and Islet biology Group, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney , Level 6, Medical Foundation Building, 92-94 Parramatta Road , Camperdown , NSW 2050 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilson K. M.","family":"Wong","sequence":"additional","affiliation":[{"name":"Diabetes and Islet biology Group, NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney , Level 6, Medical Foundation Building, 92-94 Parramatta Road , Camperdown , NSW 2050 , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2020,6,19]]},"reference":[{"key":"2022052423154240735_j_med-2020-0170_ref_001_w2aab3b7d456b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Bluestone JA, Herold K, Eisenbarth G. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature. 2010;464(7293):1293\u2013300.","DOI":"10.1038\/nature08933"},{"key":"2022052423154240735_j_med-2020-0170_ref_002_w2aab3b7d456b1b6b1ab2b1b2Aa","doi-asserted-by":"crossref","unstructured":"Shapiro AM, Lakey EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, et al. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000;343(4):230\u20138.","DOI":"10.1056\/NEJM200007273430401"},{"key":"2022052423154240735_j_med-2020-0170_ref_003_w2aab3b7d456b1b6b1ab2b1b3Aa","doi-asserted-by":"crossref","unstructured":"Sahu S, Tosh D, Hardikar AA. New sources of beta-cells for treating diabetes. J Endocrinol. 2009;202(1):13\u20136.","DOI":"10.1677\/JOE-09-0097"},{"key":"2022052423154240735_j_med-2020-0170_ref_004_w2aab3b7d456b1b6b1ab2b1b4Aa","doi-asserted-by":"crossref","unstructured":"Gangaram-Panday ST, Faas MM, de Vos P. Towards stem-cell therapy in the endocrine pancreas. Trends Mol Med. 2007;13(4):164\u201373.","DOI":"10.1016\/j.molmed.2007.02.002"},{"key":"2022052423154240735_j_med-2020-0170_ref_005_w2aab3b7d456b1b6b1ab2b1b5Aa","doi-asserted-by":"crossref","unstructured":"Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N. MiRNA-375 promotes beta pancreatic differentiation in human induced pluripotent stem (hiPS) cells. Mol Biol Rep. 2014;41(4):2055\u201366.","DOI":"10.1007\/s11033-014-3054-4"},{"key":"2022052423154240735_j_med-2020-0170_ref_006_w2aab3b7d456b1b6b1ab2b1b6Aa","doi-asserted-by":"crossref","unstructured":"Eliasson L. The small RNA miR-375\u2009\u2013\u2009a pancreatic islet abundant miRNA with multiple roles in endocrine beta cell function. Mol Cell Endocrinol. 2017;456:95\u2013101.","DOI":"10.1016\/j.mce.2017.02.043"},{"key":"2022052423154240735_j_med-2020-0170_ref_007_w2aab3b7d456b1b6b1ab2b1b7Aa","doi-asserted-by":"crossref","unstructured":"Lahmy R, Soleimani M, Sanati MH, Behmanesh M, Kouhkan F, Mobarra N. Pancreatic islet differentiation of human embryonic stem cells by microRNA overexpression. J Tissue Eng Regen Med. 2016;10(6):527\u201334.","DOI":"10.1002\/term.1787"},{"key":"2022052423154240735_j_med-2020-0170_ref_008_w2aab3b7d456b1b6b1ab2b1b8Aa","doi-asserted-by":"crossref","unstructured":"Bravo-Egana V, Rosero S,  Molano RD, Pileggi A, Ricordi C, Dom\u00ednguez-Bendala J, et al. Quantitative differential expression analysis reveals miR-7 as major islet microRNA. Biochem Biophys Res Commun. 2008;366(4):922\u20136.","DOI":"10.1016\/j.bbrc.2007.12.052"},{"key":"2022052423154240735_j_med-2020-0170_ref_009_w2aab3b7d456b1b6b1ab2b1b9Aa","doi-asserted-by":"crossref","unstructured":"Joglekar MV, Joglekar VM, Hardikar AA. Expression of islet-specific microRNAs during human pancreatic development. Gene Expression Patterns. 2009;9(2):109\u201313.","DOI":"10.1016\/j.gep.2008.10.001"},{"key":"2022052423154240735_j_med-2020-0170_ref_010_w2aab3b7d456b1b6b1ab2b1c10Aa","doi-asserted-by":"crossref","unstructured":"Lopez-Beas J, Capilla-Gonz\u00e1lez V, Aguilera Y, Mellado N, Lachaud CC, Mart\u00edn F, et al. miR-7 modulates hESC differentiation into insulin-producing beta-like cells and contributes to cell maturation. Mol Ther Nucleic Acids. 2018;12:463\u201377.","DOI":"10.1016\/j.omtn.2018.06.002"},{"key":"2022052423154240735_j_med-2020-0170_ref_011_w2aab3b7d456b1b6b1ab2b1c11Aa","doi-asserted-by":"crossref","unstructured":"Pezzolla D, L\u00f3pez-Beas J, Lachaud CC, Dom\u00ednguez-Rodr\u00edguez A, Smani T, Hmadcha T, et al. Resveratrol ameliorates the maturation process of beta-cell-like cells obtained from an pptimized differentiation protocol of human embryonic stem cells. PLoS One. 2015;10(3):e0119904.","DOI":"10.1371\/journal.pone.0119904"},{"key":"2022052423154240735_j_med-2020-0170_ref_012_w2aab3b7d456b1b6b1ab2b1c12Aa","doi-asserted-by":"crossref","unstructured":"Gershengorn MC, Hardikar AA, Wei C, Geras-Raaka E, Marcus-Samuels B, Raaka BM. Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells. Science. 2004;306(5705):2261\u20134.","DOI":"10.1126\/science.1101968"},{"key":"2022052423154240735_j_med-2020-0170_ref_013_w2aab3b7d456b1b6b1ab2b1c13Aa","doi-asserted-by":"crossref","unstructured":"Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, et al. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014;32(11):1121\u201333.","DOI":"10.1038\/nbt.3033"},{"key":"2022052423154240735_j_med-2020-0170_ref_014_w2aab3b7d456b1b6b1ab2b1c14Aa","doi-asserted-by":"crossref","unstructured":"Pagliuca FW, Millman JR, G\u00fcrtler M, Segel M, Van Dervort A, Ryu JH, et al. Generation of functional human pancreatic beta cells in vitro. Cell. 2014;159(2):428\u201339.","DOI":"10.1016\/j.cell.2014.09.040"},{"key":"2022052423154240735_j_med-2020-0170_ref_015_w2aab3b7d456b1b6b1ab2b1c15Aa","doi-asserted-by":"crossref","unstructured":"Zhou Q, Brown J, Kanarek A, Rajagopal J, Melton DA. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008;455(7213):627\u201332.","DOI":"10.1038\/nature07314"},{"key":"2022052423154240735_j_med-2020-0170_ref_016_w2aab3b7d456b1b6b1ab2b1c16Aa","doi-asserted-by":"crossref","unstructured":"Williams MD, Mitchell GM. MicroRNAs in insulin resistance and obesity. Exp Diabetes Res. 2012;2012;484696.","DOI":"10.1155\/2012\/484696"},{"key":"2022052423154240735_j_med-2020-0170_ref_017_w2aab3b7d456b1b6b1ab2b1c17Aa","unstructured":"Joglekar MV, Parekh VS, Hardikar AA. Islet-specific microRNAs in pancreas development, regeneration and diabetes. Indian J Exp Biol. 2011;49(6):401\u20138."}],"container-title":["Open Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/view\/journals\/med\/15\/1\/article-p567.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0170\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0170\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T23:22:40Z","timestamp":1653434560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/med-2020-0170\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,11,21]]},"published-print":{"date-parts":[[2020,11,21]]}},"alternative-id":["10.1515\/med-2020-0170"],"URL":"https:\/\/doi.org\/10.1515\/med-2020-0170","relation":{},"ISSN":["2391-5463"],"issn-type":[{"value":"2391-5463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,1]]}}}