Effects of High-Mobility Group A Protein Application on Canine Adipose-Derived Mesenchymal Stem CellsIn Vitro

Abstract

Multipotency and self-renewal are considered as most important features of stem cells to persist throughout life in tissues. In this context, the role of HMGA proteins to influence proliferation of adipose-derived mesenchymal stem cell (ASCs) while maintaining their multipotent and self-renewal capacities has not yet been investigated. Therefore, extracellular HMGA1 and HMGA2 application alone (10–200 ng/mL) and in combination with each other (100, 200 ng/mL each) was investigated with regard to proliferative effects on canine ASCs (cASCs) after 48 hours of cultivation. Furthermore, mRNA expression of multipotency marker genes in unstimulated and HMGA2-stimulated cASCs (50, 100 ng/mL) was analyzed by RT-qPCR. HMGA1 significantly reduced cASCs proliferation in concentrations of 10–200 ng/mL culture medium. A combination of HMGA1 and HMGA2 protein (100 and 200 ng/mL each) caused the same effects, whereas no significant effect on cASCs proliferation was shown after HMGA2 protein application alone. RT-qPCR results showed that expression levels of marker genes including KLF4, SOX2, OCT4, HMGA2, and cMYC mRNAs were on the same level in both HMGA2-protein-stimulated and -unstimulated cASCs. Extracellular HMGA protein application might be valuable to control proliferation of cASCs in context with their employment in regenerative approaches without affecting their self-renewal and multipotency abilities.

Single‐cell transcriptome profiling reveals molecular heterogeneity in human umbilical cord tissue and culture‐expanded mesenchymal stem cells

“…3D,E). Previous studies have shown that TFs such as HMGB and HMGA families are highly expressed in proliferating human MSCs and inhibiting MSC differentiation through complex transcriptional network [42]. Consistent with the previous study, HMGB1/2/3 and HMGA1/2 were also highly expressed in the proliferative UMSC1 and also interacted with BRCA1, E2F4, EZH2, and TFDP1 by TF–target interaction network analyses (Fig.…”

Mesenchymal stromal cells expressing a dominant-negative high mobility group A1 transgene exhibit improved function during sepsis

“…Although it is known that overexpression of HMGA1 is associated with cellular proliferation and neoplastic transformation, 39 it has been suggested that exposure of MSCs to extracellular HMGA1 may actually reduce proliferation. 40 Nevertheless, in the present study, dnHMGA1 Tg MSCs demonstrated less cell proliferation compared with WT MSCs, which is consistent with less growth potential in cells with disruption of the HMGA1 pathway.…”

“…HMGA proteins have been suggested to play a role in adipogenesis 37,38 ; however, Tg MSCs harvested from adult mice showed no alteration of cellular differentiation into adipocytes, osteoblasts, or chondrocytes compared with WT MSCs. Although it is known that overexpression of HMGA1 is associated with cellular proliferation and neoplastic transformation, 39 it has been suggested that exposure of MSCs to extracellular HMGA1 may actually reduce proliferation 40 . Nevertheless, in the present study, dnHMGA1 Tg MSCs demonstrated less cell proliferation compared with WT MSCs, which is consistent with less growth potential in cells with disruption of the HMGA1 pathway.…”

“…At 24 h after surgery, lungs were harvested from each group and total RNA extracted. Quantitative real time PCR (qRT-PCR) was assessed for the levels of (A) IL-6, (B) MIP-2, and (Continued on next page) has been suggested that exposure of MSCs to extracellular HMGA1 may actually reduce proliferation 40. Nevertheless, in the present study, dnHMGA1 Tg MSCs demonstrated less cell proliferation compared with WT MSCs, which is consistent with less growth potential in cells with disruption of the HMGA1 pathway.It has previously been shown that elevated levels of HMGA1were associated with increased production of cellular reactive oxygen species, and decreased efficiency of mitochondrial DNA repair due to oxidative injury 41.…”