{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/39609"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/39609","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Tracing of Alpha-to-Beta Cell Transition Following Treatment with CHIR-Injected Human Multipotent Stromal Cell Secreted Proteins","abstract":"Diabetes is a global epidemic projected to affect over 628.6 million people by 2045. Current insulin therapy manages symptoms but cannot restore endogenous beta cell function. Regenerative strategies have demonstrated beta-cell neogenesis following ablation; however, the cellular mechanisms driving islet regeneration remain unclear. Previous work from the Hess Lab has shown that human bone marrow-derived multipotent stromal cells (BMMSCs), bioengineered via WNT pathway activation (CHIR+ conditioned media; CM), secrete factors that promote beta-cell recovery in streptozotocin (STZ) treated NOD/SCID mice. Here, we investigated whether this regeneration process involves alpha-to-beta cell conversion, using a Glucagon-iCre;Rosa26-TdTomato (GcgxTdT) lineage-tracing model. Following STZ-induced hyperglycemia induction and intrapancreatic CM injection, CHIR+ CM transiently increased TdTomato+/insulin+ cells at Day 14. However, sustained improvements in glycemia or glucose tolerance were not observed by Day 28. These findings suggest MSC-derived CM did not enhance long-term alpha-to-beta conversion to restore islet function.","abstract_html":"Diabetes is a global epidemic projected to affect over 628.6 million people by 2045. Current insulin therapy manages symptoms but cannot restore endogenous beta cell function. Regenerative strategies have demonstrated beta-cell neogenesis following ablation; however, the cellular mechanisms driving islet regeneration remain unclear. Previous work from the Hess Lab has shown that human bone marrow-derived multipotent stromal cells (BMMSCs), bioengineered via WNT pathway activation (CHIR+ conditioned media; CM), secrete factors that promote beta-cell recovery in streptozotocin (STZ) treated NOD/SCID mice. Here, we investigated whether this regeneration process involves alpha-to-beta cell conversion, using a Glucagon-iCre;Rosa26-TdTomato (GcgxTdT) lineage-tracing model. Following STZ-induced hyperglycemia induction and intrapancreatic CM injection, CHIR+ CM transiently increased TdTomato+/insulin+ cells at Day 14. However, sustained improvements in glycemia or glucose tolerance were not observed by Day 28. These findings suggest MSC-derived CM did not enhance long-term alpha-to-beta conversion to restore islet function.","abstract_has_math":false,"creators":["Sharma, Ajaya"],"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":2026,"date_issued":"2026-02-18","date_published":"2026-02-18","updated_at":"2026-07-27T21:55:54Z","subjects":["Diabetes","Multipotent Stromal Cells","Alpha Cells","Beta Cell Regeneration","Lineage Tracing","Conditioned Media"],"languages":["en"],"rights":["Attribution-NoDerivatives 4.0 International"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/39609","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":["Sharma, Ajaya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-04-30T12:54:00Z"]},{"key":"dc:date.issued","label":"Date","values":["2026-02-18"]},{"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"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Western Ontario"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Diabetes","Multipotent Stromal Cells","Alpha Cells","Beta Cell Regeneration","Lineage Tracing","Conditioned Media"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Attribution-NoDerivatives 4.0 International"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/39609"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Diabetes is a global epidemic projected to affect over 628.6 million people by 2045. Current insulin therapy manages symptoms but cannot restore endogenous beta cell function. Regenerative strategies have demonstrated beta-cell neogenesis following ablation; however, the cellular mechanisms driving islet regeneration remain unclear. Previous work from the Hess Lab has shown that human bone marrow-derived multipotent stromal cells (BMMSCs), bioengineered via WNT pathway activation (CHIR+ conditioned media; CM), secrete factors that promote beta-cell recovery in streptozotocin (STZ) treated NOD/SCID mice. Here, we investigated whether this regeneration process involves alpha-to-beta cell conversion, using a Glucagon-iCre;Rosa26-TdTomato (GcgxTdT) lineage-tracing model. Following STZ-induced hyperglycemia induction and intrapancreatic CM injection, CHIR+ CM transiently increased TdTomato+/insulin+ cells at Day 14. However, sustained improvements in glycemia or glucose tolerance were not observed by Day 28. These findings suggest MSC-derived CM did not enhance long-term alpha-to-beta conversion to restore islet function."]},{"key":"dc:title","label":"Title","values":["Tracing of Alpha-to-Beta Cell Transition Following Treatment with CHIR-Injected Human Multipotent Stromal Cell Secreted Proteins"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hess, David A."],"dc:creator":["Sharma, Ajaya"],"dc:date.accessioned":["2026-04-30T12:54:00Z"],"dc:date.issued":["2026-02-18"],"dc:description.abstract":["Diabetes is a global epidemic projected to affect over 628.6 million people by 2045. Current insulin therapy manages symptoms but cannot restore endogenous beta cell function. Regenerative strategies have demonstrated beta-cell neogenesis following ablation; however, the cellular mechanisms driving islet regeneration remain unclear. Previous work from the Hess Lab has shown that human bone marrow-derived multipotent stromal cells (BMMSCs), bioengineered via WNT pathway activation (CHIR+ conditioned media; CM), secrete factors that promote beta-cell recovery in streptozotocin (STZ) treated NOD/SCID mice. Here, we investigated whether this regeneration process involves alpha-to-beta cell conversion, using a Glucagon-iCre;Rosa26-TdTomato (GcgxTdT) lineage-tracing model. Following STZ-induced hyperglycemia induction and intrapancreatic CM injection, CHIR+ CM transiently increased TdTomato+/insulin+ cells at Day 14. However, sustained improvements in glycemia or glucose tolerance were not observed by Day 28. These findings suggest MSC-derived CM did not enhance long-term alpha-to-beta conversion to restore islet function."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/39609"],"dc:language.iso":["en"],"dc:publisher":["The University of Western Ontario"],"dc:rights":["Attribution-NoDerivatives 4.0 International"],"dc:subject":["Diabetes","Multipotent Stromal Cells","Alpha Cells","Beta Cell Regeneration","Lineage Tracing","Conditioned Media"],"dc:title":["Tracing of Alpha-to-Beta Cell Transition Following Treatment with CHIR-Injected Human Multipotent Stromal Cell Secreted Proteins"],"dc:type":["thesis"],"thesis:degree_discipline":["Physiology and Pharmacology"],"thesis:degree_name":["M Sc"],"thesis:institution_name":["The University of Western Ontario"]},"updated_at":"2026-07-27T21:55:54Z"}