IL-1β + TGF-β2 dual-licensed mesenchymal stem cells have reduced major histocompatibility class I expression and positively modulate tenocyte migration, metabolism, and gene expression.

Autor:	Koch DW; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC., Froneberger A; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC., Berglund A; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC., Connard S; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC., Souther A; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC., Schnabel LV; Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC.; Comparative Medicine Institute, North Carolina State University, Raleigh, NC.
Jazyk:	angličtina
Zdroj:	Journal of the American Veterinary Medical Association [J Am Vet Med Assoc] 2024 Apr 01; Vol. 262 (S1), pp. S61-S72. Date of Electronic Publication: 2024 Apr 01 (Print Publication: 2024).
DOI:	10.2460/javma.23.12.0708
Abstrakt:	Objective: The study objectives were to 1) determine the mesenchymal stem cell (MSC) surface expression of major histocompatibility complex (MHC) class I and transcriptome-wide gene expression changes following IL-1β + TGF-β2 dual licensing and 2) evaluate if IL-1β + TGF-β2 dual-licensed MSCs had a greater ability to positively modulate tenocyte function compared to naive MSCs. Sample: Equine bone marrow-derived MSCs from 6 donors and equine superficial digital flexor tenocytes from 3 donors. Methods: Experiments were performed in vitro. Flow cytometry and bulk RNA sequencing were utilized to determine naive and dual-licensed MSC phenotype and transcriptome-wide changes in gene expression. Conditioned media were generated from MSCs and utilized in tenocyte cell culture assays as a method to determine the effect of MSC paracrine factors on tenocyte function. Results: Dual-licensed MSCs have a reduced expression of MHC class I and exhibit enrichment in functional pathways associated with the extracellular matrix, cell signaling, and tissue development. Additionally, dual-licensed MSC-conditioned media significantly improved in vitro tenocyte migration and metabolism to a greater degree than naive MSC-conditioned media. In tenocytes exposed to IL-1β, dual-licensed conditioned media also positively modulated tenocyte gene expression. Clinical Relevance: Our data indicate that conditioned media containing paracrine factors secreted from dual-licensed MSCs significantly modulates in vitro tenocyte function, which may confer benefits in vivo to healing tendons following injury. Additionally, due to reduced MHC class I expression in dual-licensed MSCs, this technique may also provide an avenue to provide an effective "off-the-shelf" allogenic source of MSCs.
Databáze:	MEDLINE
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