Event

PhD Dissertation Defense: Mitsuo Kumagai

Monday, October 26, 2026
9:45 a.m.
AJC 3104 (3rd floor conference room)
Debbie Chu
301 405 8268
dgchu@umd.edu

Title: Enhanced 3D Differentiation, Culture, and Maturation of iMSCs for Cell-based Medicine

Committee members:
Dr. Helim Aranda-Espinoza, Chair
Dr. Steven Jay
Dr. Wenquan Ou
Dr. Kimberly Stroka
Dr. Carol L. Keefer, Dean's Representative

Abstract:
Mesenchymal stem cells (MSCs) are a powerful tool in regenerative medicine due to their immunomodulatory capabilities, proangiogenic effects, and ability to differentiate into multiple lineages. However, donor-derived MSCs suffer from major translational hurdles, including donor-to-donor variability, limited scalability, and reliance on variable, undefined, xenogeneic, or otherwise cost-prohibitive media components for expansion. Human induced pluripotent stem cell-derived MSCs (iMSCs) have emerged as a promising alternative, offering enhanced scalability, greater phenotypic consistency, and the potential for autologous therapies. Yet, current methods for iMSC differentiation, expansion, and maturation are inefficient, poorly defined, and incompatible with large-scale clinical production.

This work establishes methods to overcome these limitations by developing a standardized, high-yield, and clinically translatable workflow for iMSC generation and maturation. First, we enhanced iMSC differentiation using poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate key pathway inhibitors (CHIR99021 and BIO), enabling sustained release without the need for cytotoxic solvents like dimethyl sulfoxide (DMSO) to dissolve them in the medium for iMSC differentiation. This approach is designed to improve viability, yield, and functional quality of iMSCs in 3D differentiation and culture. Second, we established a fully defined and xenogeneic-free 3D culture system using a cold-responsive micropatterned device (crMPD) and defined laminin to generate uniform, high-quality 3D iPSC spheroids with increased yield. Finally, we evaluated a cost-effective, chemically defined medium to support large-scale iMSC expansion and maturation while maintaining viability, proliferation, and MSC phenotype and functionality. Collectively, this work establishes a platform to deliver a reproducible, scalable, and clinically viable method for producing high-quality iMSCs, ultimately supporting the development of more consistent and effective cell-based therapies for a broad range of diseases and conditions.