{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/30490"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/30490","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Developing a model to assess the contribution of cytokeratin 19-expressing cells during multipotent stromal cell-induced islet regeneration","abstract":"Previously, pharmacological activation of Wnt-signaling in human bone marrow-derived multipotent stromal cells (hMSC) generated conditioned media (CM) that promoted β-cell regeneration in streptozotocin-treated mice. Ductal-derived endocrine progenitors, which have been shown to generate β-cells following pancreatic injury, represent a candidate for the ‘signal-receiving cell’. Ductal (CK19+) cells from mice pancreata obtained by purification of live Dolichos Biflorus Agglutinin lectin+ cells and cultured in minimal media supplemented with Untreated, Wnt-activated, or Wnt-inhibited CM demonstrated a significantly increased proportion of EdU+/CK19+ cells following 48-hours of supplementation but no endocrine phenotype acquisition. Lineage-tracing CK19-CreERT;Ai9(RCL-tdT) mice treated with tamoxifen (single dose) demonstrated specific labeling of pancreatic CK19+ cells. Streptozotocin treatment (60 mg/kg/day, 5 days) resulted in decreased β-cell mass, islet density, and insulin+ cell frequency, as well as impaired glucose tolerance and increased pancreatic leukocyte infiltration. This model will be used in future studies to lineage-trace CK19+ cell contribution during hMSC CM-induced islet regeneration.","abstract_html":"Previously, pharmacological activation of Wnt-signaling in human bone marrow-derived multipotent stromal cells (hMSC) generated conditioned media (CM) that promoted β-cell regeneration in streptozotocin-treated mice. Ductal-derived endocrine progenitors, which have been shown to generate β-cells following pancreatic injury, represent a candidate for the ‘signal-receiving cell’. Ductal (CK19+) cells from mice pancreata obtained by purification of live Dolichos Biflorus Agglutinin lectin+ cells and cultured in minimal media supplemented with Untreated, Wnt-activated, or Wnt-inhibited CM demonstrated a significantly increased proportion of EdU+/CK19+ cells following 48-hours of supplementation but no endocrine phenotype acquisition. Lineage-tracing CK19-CreERT;Ai9(RCL-tdT) mice treated with tamoxifen (single dose) demonstrated specific labeling of pancreatic CK19+ cells. Streptozotocin treatment (60 mg/kg/day, 5 days) resulted in decreased β-cell mass, islet density, and insulin+ cell frequency, as well as impaired glucose tolerance and increased pancreatic leukocyte infiltration. This model will be used in future studies to lineage-trace CK19+ cell contribution during hMSC CM-induced islet regeneration.","abstract_has_math":false,"creators":["Ananthan, Brianna"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Physiology and Pharmacology","degree_department":null,"school":null,"contributors":[],"advisors":["Hess, David A."],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-09-03","date_published":"2020-09-03","updated_at":"2026-07-27T21:56:16Z","subjects":["Multipotent stromal cell","Cell-free therapy","Beta cell regeneration","Ductal cell","Diabetes","Lineage tracing"],"languages":["en_ca"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/30490","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hess, David A."]},{"key":"dc:creator","label":"Author","values":["Ananthan, Brianna"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-07-10T18:41:28Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-07-10T18:41:28Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-09-03"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology and Pharmacology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Multipotent stromal cell","Cell-free therapy","Beta cell regeneration","Ductal cell","Diabetes","Lineage tracing"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_ca"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/30490"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Collaborative Specialization: Developmental Biology","The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."]},{"key":"dc:description.abstract","label":"Abstract","values":["Previously, pharmacological activation of Wnt-signaling in human bone marrow-derived multipotent stromal cells (hMSC) generated conditioned media (CM) that promoted β-cell regeneration in streptozotocin-treated mice. Ductal-derived endocrine progenitors, which have been shown to generate β-cells following pancreatic injury, represent a candidate for the ‘signal-receiving cell’. Ductal (CK19+) cells from mice pancreata obtained by purification of live Dolichos Biflorus Agglutinin lectin+ cells and cultured in minimal media supplemented with Untreated, Wnt-activated, or Wnt-inhibited CM demonstrated a significantly increased proportion of EdU+/CK19+ cells following 48-hours of supplementation but no endocrine phenotype acquisition. Lineage-tracing CK19-CreERT;Ai9(RCL-tdT) mice treated with tamoxifen (single dose) demonstrated specific labeling of pancreatic CK19+ cells. Streptozotocin treatment (60 mg/kg/day, 5 days) resulted in decreased β-cell mass, islet density, and insulin+ cell frequency, as well as impaired glucose tolerance and increased pancreatic leukocyte infiltration. This model will be used in future studies to lineage-trace CK19+ cell contribution during hMSC CM-induced islet regeneration."]},{"key":"dc:title","label":"Title","values":["Developing a model to assess the contribution of cytokeratin 19-expressing cells during multipotent stromal cell-induced islet regeneration"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hess, David A."],"dc:creator":["Ananthan, Brianna"],"dc:date.accessioned":["2025-07-10T18:41:28Z"],"dc:date.available":["2025-07-10T18:41:28Z"],"dc:date.issued":["2020-09-03"],"dc:description":["Collaborative Specialization: Developmental Biology","The thesis cover page in the PDF document includes references to Western University’s previous institutional repository platform, known as Scholarship@Western, and links to that platform (beginning with ir.lib.uwo.ca). In citing or referring to this thesis, use the DOI or handle from this page instead. Sample citation: Author name, \"Thesis title.\" (Year). Western University Open Repository. https://doi.org/10.71858/123456."],"dc:description.abstract":["Previously, pharmacological activation of Wnt-signaling in human bone marrow-derived multipotent stromal cells (hMSC) generated conditioned media (CM) that promoted β-cell regeneration in streptozotocin-treated mice. Ductal-derived endocrine progenitors, which have been shown to generate β-cells following pancreatic injury, represent a candidate for the ‘signal-receiving cell’. Ductal (CK19+) cells from mice pancreata obtained by purification of live Dolichos Biflorus Agglutinin lectin+ cells and cultured in minimal media supplemented with Untreated, Wnt-activated, or Wnt-inhibited CM demonstrated a significantly increased proportion of EdU+/CK19+ cells following 48-hours of supplementation but no endocrine phenotype acquisition. Lineage-tracing CK19-CreERT;Ai9(RCL-tdT) mice treated with tamoxifen (single dose) demonstrated specific labeling of pancreatic CK19+ cells. Streptozotocin treatment (60 mg/kg/day, 5 days) resulted in decreased β-cell mass, islet density, and insulin+ cell frequency, as well as impaired glucose tolerance and increased pancreatic leukocyte infiltration. This model will be used in future studies to lineage-trace CK19+ cell contribution during hMSC CM-induced islet regeneration."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/30490"],"dc:language.iso":["en_ca"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Multipotent stromal cell","Cell-free therapy","Beta cell regeneration","Ductal cell","Diabetes","Lineage tracing"],"dc:title":["Developing a model to assess the contribution of cytokeratin 19-expressing cells during multipotent stromal cell-induced islet regeneration"],"dc:type":["thesis"],"thesis:degree_discipline":["Physiology and Pharmacology"],"thesis:degree_name":["M Sc"]},"updated_at":"2026-07-27T21:56:16Z"}