Tracing of Alpha-to-Beta Cell Transition Following Treatment with CHIR-Injected Human Multipotent Stromal Cell Secreted Proteins

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology and Pharmacology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2026

Author dc:creator

• Sharma, Ajaya

Advisor dc:contributor.advisor

• Hess, David A.

• Diabetes
• Multipotent Stromal Cells
• Alpha Cells
• Beta Cell Regeneration
• Lineage Tracing
• Conditioned Media

Statement dc:rights

• Attribution-NoDerivatives 4.0 International

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/39609

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/39609