Abstract
Mesenchymal stem/stromal cells (MSCs) have been investigated extensively for their immunotherapeutic and regenerative properties, which may differ by cell source. In MSCs harvested from donors matched for sex, age, and body mass index, we compared the proliferative and migration functions of liver-derived MSCs (L-MSCs) and adipose tissue-derived MSCs (A-MSCs) (n = 6 donors each). Cellular senescence was evaluated by senescence-associated beta-galactosidase enzyme activity and expression of senescence-associated secretory phenotype (SASP) factors using real-time quantitative polymerase chain and by western blot assay. The pro-angiogenic and reparative potency of MSCs was compared by co-culturing MSCs with injured human umbilical vein endothelial cells (HUVEC). The proliferation and migration properties were similar in L-MSCs and A-MSCs. Although cell cycle arrest and SASP genes were similarly expressed in both MSCs, tumor necrosis factor alpha gene and protein expression were significantly downregulated in L-MSCs. In co-cultured injured HUVEC, A-MSCs restored significantly more tubes and tube connections than L-MSCs. Therefore, despite many functional similarities between L-MSCs and A-MSCs, L-MSCs have enhanced immunomodulatory properties, while A-MSCs appear to have better pro-angiogenic and vascular reparative potency. Availability of a broad range of cellular options might enable selecting cell-based therapy appropriate for the specific underlying disease.
Highlights
Mesenchymal stem/stromal cells (MSCs) are non-hematopoietic multipotent cells with the inherent ability to self-renew and differentiate into tissues of mesenchymal origin (Dominici et al, 2006)
In attempt to identify the liver components that contribute to its tolerogenic microenvironment, we have recently isolated and expanded human liver MSCs (L-MSCs) in vitro
To characterize the cellular properties of L-MSCs and identify their unique properties relative to MSCs derived from other tissues, here we compared them to the commonly investigated and well-characterized adipose tissue-derived MSCs (A-MSCs)
Summary
Mesenchymal stem/stromal cells (MSCs) are non-hematopoietic multipotent cells with the inherent ability to self-renew and differentiate into tissues of mesenchymal origin (Dominici et al, 2006). They have essential roles in tissue repair and regeneration through their anti-apoptotic activity and stimulation of angiogenesis, as well as notable immunomodulatory activities (Han et al, 2019). MSCs have been demonstrated to regulate immune reactivity through paracrine mechanisms by inhibiting both innate and adaptive responses (Zhou et al, 2019) Their impact on lymphocytes, macrophages, dendritic cells, and natural killer (NK) cells has been investigated extensively (Wang et al, 2014; Najar et al, 2016). L-MSCs may be better candidates for cellular therapies
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