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2022 Abstracts

Effects of Basic Fibroblast Growth Factor on the Phenotype & Expansion of Human Bone Marrow-derived Mesenchymal Stem/Stromal Cells

Presenter: Tavie Parker
Authors: Tavie Parker, Celia Dunn, Makoto Kondo, Sumako Kameishi, David Grainger, Teruo Okano
Faculty Advisor: David Grainger
Institution: University of Utah

Mesenchymal stem/stromal cells (MSCs) attract significant clinical interest for their ability to modulate the host immune system and repair/replace damaged tissue. These characteristics have motivated over 900 clinical trials investigating MSC-based therapiesto treata range of diseases.Use of MSCs in cell-based therapeutics requiresin vitroexpansion and banking, necessitating the implementation of optimized culture conditions for clinical scale production. For MSCs, the culture process commonly involves addition ofexogenousbasic fibroblast growth factor (bFGF)topromote MSC proliferation and improvecellproduction scalability. However, the effects of bFGF onboth cellphenotype and the resulting therapeutic potential of MSCsremain undercharacterized.To determine the impact of bFGF on the MSC phenotype, we cultured human bone marrow-derived MSCs (hBMSCs) in the presence and absence of bFGFand performedin vitrotri-lineage differentiation assays andflow cytometryanalysisfollowing culture. This approachallowedcharacterizationand comparison ofthe hBMSC expansion, morphology, differentiation potential, and surface marker expression between the experimental groups. We found that bFGF has a substantial effect on hBMSC surface marker expression, upregulating human leukocyte antigen DR (HLA-DR)from 1.59% expression to 63.1% expression.Despite the advantages of adding bFGF to enhancein vitrohBMSCproliferation, this upregulation of HLA-DRmay increaserisksof allogeneic immunogenicityupon MSC dosingand host rejection of hBMSCsin vivo. Understanding the full range of effects of bFGF on hBMSCs has potential practical implications for clinical scale production and therapeutic benefit of MSC-based therapies.