Comparison of bone marrow‑vs. adipose tissue‑derived mesenchymal stem cells for attenuating liver fibrosis

Abstract

Mesenchymal stem cell (MSC) therapy has emerged as a potential novel method of treating liver fibrosis. To date, bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AD-MSCs) have not been analyzed with respect to their ability to combat liver fibrosis. The present study aimed to compare the capabilities of BM-MSCs and AD-MSCs in the treatment of liver fibrosis. BM-MSCs and AD-MSCs were taken from male Sprague-Dawley rats and cultured. Hepatic stellate cells (HSCs) were co-cultured with either BM-MSCs or AD-MSCs, and the effects of BM-MSCs or AD-MSCs on the proliferation, activation and apoptosis of HSCs were determined. The secretion of a selected group of cytokines by BM-MSCs and AD-MSCs was measured using enzyme-linked immunosorbent assays. Using a CCl4-induced liver fibrosis animal model, the anti-inflammatory and anti-fibrotic effects of BM-MSCs or AD-MSCs against liver fibrosis in vivo were evaluated. The morphological examination and analysis of specific surface markers confirmed the successful preparation of BM-MSCs and AD-MSCs. Furthermore, the proliferation, activation and apoptosis of HSCs were significantly inhibited by BM-MSCs and AD-MSCs, with statistically greater reductions achieved by AD-MSCs compared with BM-MSCs. Direct comparison of the secretion of selected cytokines by BM-MSCs and AD-MSCs revealed that significantly higher levels of nerve growth factor and transforming growth factor-β1 were secreted in the AD-MSC culture medium, whereas levels of vascular endothelial growth factor and interleukin-10 did not differ significantly between AD-MSCs and BM-MSCs. In vivo studies using a CCl4-induced liver fibrosis model demonstrated that inflammatory activity and fibrosis staging scores were significantly lower in the MSC-treated groups compared with controls. Although AD-MSCs improved anti-inflammatory and anti-fibrotic effects compared with BM-MSCs, these differences were not significant. Thus, the current study demonstrated that BM-MSCs and AD-MSCs are similarly effective at attenuating liver fibrosis by inhibiting the activation and proliferation of HSCs, as well as promoting the apoptosis of HSCs.

Therapeutic Potential of Autologous Adipose-Derived Stem Cells for the Treatment of Liver Disease

“…Currently, several experimental animal models of liver injury exist and are described in the literature [44]. In these studies, the most commonly used approach to induce experimental liver injury in mice or rats is the periodic administration of toxic agents, such as carbon tetrachloride (CCl4) or thioacetamide (TAA) [8,45,46]. Although the CCl4 and TAA treatments generate well-established animal models of hepatic disease that show pathological characteristics consistent with that of acute liver failure, these have a number of disadvantages that limit the conclusions that can be drawn from these studies [44].…”

Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

“…They can be obtained from various types of tissue, with bone marrow and adipose tissue being the main sources used in therapy [7]. Notably, adipose tissue-derived mesenchymal stem cells (ASCs) offer several advantages with respect to bone marrow-derived mesenchymal stem cells, namely: (i) higher proliferation capacity, (ii) secretion of growth factors related to chondrogenic differentiation (IGF, bFGF and TGF-β1), (iii) anti-inflammatory properties, (iv) long-term culture stability in the differentiation state, and (v) the large numbers of cells that may be harvested from patients with minimally invasive procedures [8][9][10][11][12].…”

Impact of Mesenchymal Stromal Cells and Their Extracellular Vesicles in a Rat Model of Kidney Rejection

“…This slight amelioration of renal function was associated with a histological improvement, which was not sufficient to counteract the reject evolution. To try to do an explanation about this differences in immunoreactivity that we observed in this setting, it is that although they have similar surface molecular markers, and immunomodulatory capacities (Yoo et al, 2009;Pendleton et al, 2013;Hao et al, 2017), their differentiation capacity (Liu et al, 2007) as well as, the secretion of paracrine factors is different (Togel et al, 2005;Hsiao et al, 2012). It is important to highlight that most of these studies about their characterization are in vitro models with a relative translatability to a complex in vivo models.…”