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. 1. Introduction Mesenchymal stem cells (MSCs) are considered as one source of progenitor cells for therapeutic approaches in regenerative medicine. Although MSCs are commonly derived from bone marrow (BMSCs) [1], adipose-tissue-derived MSCs (ASCs) might be used as an alternative multipotent cell source [2–4]. Similar to BMSCs, ASCs have been also evaluated for multilineage differentiation capacities including differentiation into a chondrogenic [5, 6], osteogenic [5–7], adipogenic [5–7], neurogenic [8, 9], myogenic [6, 8, 10], angiogenic [11], and cardiomyogenic [10] lineage. In contrast to bone marrow, a large amount of adipose tissue can easily be obtained via less invasive and harmful methods making the use of ASCs as a source of stem cells very attractive [12]. Furthermore, it has recently been reported that ASCs have stronger capabilities than BMSCs to maintain their phenotype and multipotency potential even after 25 passages of in vitro cultivation [10]. The self-renewal and multipotency characteristics through regular and organized cell division are the most important features of stem cells to persist throughout life in tissues. These features are
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