(P23-44-26) Utility of Umbilical Cord Mesenchymal Stem Cells to Model Hepatic Stellate-Like Cells and Early Features of MASLD: The Healthy Start Study

Sunday, July 26, 2026

9:30 AM - 10:30 AM ET

Location: Poster Board C-44

Presenting Author(s)

AW

Anthony A. Wang, MD, PhD (he/him/his)

Assistant Professor
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States

Co-Author(s)

SK

Suzanna Kafer

University of Colorado Anschutz Medical Campus, Colorado, United States
DD

Dana Dabelea, MD, PhD

Conrad M. Riley Endowed Professor of Epidemiology, Professor of Pediatrics, and Director of the Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center)
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
SW

Stephanie Wesolowski

University of Colorado Anschutz Medical Campus, Colorado, United States
Kristen E. Boyle, PhD

Associate Professor
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States

Disclosure(s):

Anthony A. Wang, MD, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly thought to have early life origins, but human studies are constrained by limited access to relevant tissues. As mesenchymal stem cells give rise to hepatic stellate cells, our objective was to demonstrate that umbilical cord derived mesenchymal stem cells (UC-MSCs) can be differentiated to hepatic stellate-like cells as a novel neonate-derived model to investigate early life MASLD drivers.

Methods: We tested differentiation of UC-MSCs to stellate-like cells in a cell line from our existing biorepository (Healthy Start Study, n=140). We differentiated UC-MSCs through initiation (day [d] 0-4: exogenous bone morphogenetic protein 4, fibroblast growth factor 2, vascular endothelial growth factor, hepatocyte growth factor), maintenance (d4-10: B27, insulin-transferrin-selenium-ethanolamine, retinoic acid, rosiglitazone, dexamethasone), and activation (d10-16: transforming growth factor-beta). We measured mRNA content (qPCR) of PDGFRB, PCDH7, COL1A1, ACTA2, and PPARG in two experimental replicates on d0, d4, d10, and d16. We conducted flow cytometry to measure surface expression of platelet-derived growth factor beta (PDGFR-β) with CD140b-PE. We gated live, single cells to identify percent expressing PDGFR-β, with isotype control as negative reference.

Results: mRNA content of stellate cell markers all increased from d0 to d10 of differentiation: PDGFRB (17-fold), PCDH7 (9-fold), COL1A1 (7-fold), and ACTA2 (4-fold). PPARG, an index of quiescent stellate cells, displayed a robust increase in mRNA content from d0 to d10 (62-fold), which then decreased by d16 (6-fold higher d0), a pattern characteristic of activated stellate cells. By flow cytometry, percent of cells with surface expression of PDGFR-β increased throughout differentiation: d0=7.1%, d4=26.8%, d10=99.1%, d16=99.9%.

Conclusions: Observed changes in mRNA expression are consistent with other reported stellate cell models (e.g., iPSC, primary stellate cells). Taken together, with near-complete acquisition of PDGFR-β surface expression, our findings indicate successful progression toward a stellate-like phenotype, demonstrating the feasibility of differentiating UC-MSCs into hepatic stellate-like cells using a staged, 16-day protocol.

Funding Sources: NIH T32, NORC P&F, Healthy Start