Wharton's Jelly-Derived Mesenchymal Stem Cells with High Aurora Kinase A Expression Show Improved Proliferation, Migration, and Therapeutic Potential.
Sun Jeong KimSang Eon ParkJang Bin JeongShin Ji OhAlee ChoiYun Hee KimSuk Joo ChoiSoo Young OhGyu Ha RyuHong Bae JeonJong Wook ChangPublished in: Stem cells international (2022)
Mesenchymal stem cells (MSCs) are effective therapeutic agents that contribute to tissue repair and regeneration by secreting various factors. However, donor-dependent variations in MSC proliferation and therapeutic potentials result in variable production yields and clinical outcomes, thereby impeding MSC-based therapies. Hence, selection of MSCs with high proliferation and therapeutic potentials would be important for effective clinical application of MSCs. This study is aimed at identifying the upregulated genes in human Wharton's jelly-derived MSCs (WJ-MSCs) with high proliferation potential using mRNA sequencing. Aurora kinase A (AURKA) and dedicator of cytokinesis 2 (DOCK2) were selected as the upregulated genes, and their effects on proliferation, migration, and colony formation of the WJ-MSCs were verified using small interfering RNA (siRNA) techniques. mRNA expression levels of both the genes were positively correlated with the proliferation capacity of WJ-MSCs. Moreover, AURKA from human WJ-MSCs regulated the antiapoptotic effect of skeletal muscle cells by upregulating the chemokine (C motif) ligand (XCL1); this was further confirmed in the mdx mouse model. Taken together, the results indicated that AURKA and DOCK2 can be used as potential biomarkers for proliferation and migration of human WJ-MSCs. In particular, human WJ-MSCs with high expression of AURKA might have therapeutic efficacy against muscle diseases, such as Duchenne muscular dystrophy (DMD).
Keyphrases
- mesenchymal stem cells
- umbilical cord
- duchenne muscular dystrophy
- endothelial cells
- signaling pathway
- skeletal muscle
- bone marrow
- induced pluripotent stem cells
- genome wide
- pluripotent stem cells
- poor prognosis
- stem cells
- mouse model
- cell therapy
- type diabetes
- gene expression
- cell death
- protein kinase
- oxidative stress
- metabolic syndrome
- cell proliferation
- binding protein
- endoplasmic reticulum stress
- cancer therapy