{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:42:19Z","timestamp":1782258139111,"version":"3.54.5"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,11,3]],"date-time":"2021-11-03T00:00:00Z","timestamp":1635897600000},"content-version":"vor","delay-in-days":596,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100008478","name":"Wake Forest School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH\/NIDDK STTR","doi-asserted-by":"publisher","award":["R42DK105593"],"award-info":[{"award-number":["R42DK105593"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008478","name":"Wake Forest School of Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R42DK105593"],"award-info":[{"award-number":["R42DK105593"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Transplantation of neural stem cells is a promising approach in treatment of intestinal dysfunctionality. The interstitial cells of Cajal (ICCs) are also critical in conditions such as pyloric dysfunctionality and gastroparesis. The objective of this study was to replenish neurons and ICCs in a dysfunctional pylorus as cell-based therapy to restore functionality. ICCs and enteric neural progenitor cells (NPCs) were isolated from rat duodenum and transduced with fluorescent proteins. Rat pylorus was harvested, and an ex-vivo neuromuscular dysfunctional model was developed by selective ablation of neurons and ICCs via chemical treatments. Cellular repopulation and restoration of motility were assessed by immunohistochemistry, qPCR, and functional analysis after delivery of fluorescently tagged cells. Chemical treatment of pylorus resulted in significant depletion of ICCs (67%, P = .0024; n = 3) and neural cells (83%, P = .0012; n = 3). Delivered ICCs and NPCs survived and integrated with host muscle layers. Co-injection of ICCs with NPCs exhibited 34.4% (P = .0004; n = 3) and 61.0% (P = .0003; n = 3) upregulation of ANO1 and \u03b2III tubulin, respectively. This regeneration resulted in the restoration of agonist-induced excitatory contraction (82%) and neuron evoked relaxation (83%). The functional studies with specific neuronal nitric oxide (NO) synthase blocker confirmed that restoration of relaxation was NO mediated and neuronally derived. The simultaneous delivery of ICCs observed 35.7% higher neuronal differentiation and functional restoration compared with injection of NPCs alone. Injected NPCs and ICCs integrated into the dysfunctional ex vivo pylorus tissues and restored neuromuscular functionality. The co-transplantation of NPCs and ICCs can be used to treat neurodegenerative disorders of the pylorus.<\/jats:p>\n               <jats:sec>\n                  <jats:title\/>\n                  <jats:p>Significance statement In regenerative medicine, it is possible to use the patient\u2019s own interstitial cells of Cajal (ICCs) and neural progenitor cells (NPCs) to be injected into the pylorus as cellular therapy. The functional ex vivo diseased model of the pylorus was developed, and ICCs and NPCs delivered as treatments for neuromuscular dysfunctionality. Detailed quantitative and qualitative analysis confirmed reinstatement and restoration of functionality. The current preliminary study with the ex vivo diseased model proposed the next level of cell therapy for the treatment of gastroparesis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1002\/sctm.19-0316","type":"journal-article","created":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T11:46:22Z","timestamp":1584445582000},"page":"713-723","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional restoration of ex vivo model of pylorus: Co-injection of neural progenitor cells and interstitial cells of Cajal"],"prefix":"10.1093","volume":"9","author":[{"given":"Prabhash","family":"Dadhich","sequence":"first","affiliation":[{"name":"1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"},{"name":"2 Program in Neuro-Gastroenterology and Motility, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil N.","family":"Bitar","sequence":"additional","affiliation":[{"name":"1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina"},{"name":"2 Program in Neuro-Gastroenterology and Motility, Wake Forest School of Medicine, Winston-Salem, North Carolina"},{"name":"3 Section on Gastroenterology, Wake Forest School of Medicine, Winston-Salem, North Carolina"},{"name":"4 Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,17]]},"reference":[{"issue":"1","key":"2022022809314042400_sct312680-bib-0001","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/ajg.2012.373","article-title":"Clinical guideline: management of 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