scholarly journals Adipose tissue-derived mesenchymal stem cells ameliorate experimental acute colitis in rats

Author(s):  
Seyed Jalil Masoumi ◽  
Negar Hassanshahi ◽  
Seyed-Mohammad Kazem Hosseini-Asl ◽  
Davood Mehrabani ◽  
Seyedeh-Sara Hashemi ◽  
...  

Abstract Complete treatment of ulcerative colitis (UC) is still difficult, while conventional therapies have various adverse effects. Mesenchymal stem cells (MSCs) have anti-inflammatory and immunomodulatory properties to be a therapeutic candidate for UC. We evaluated therapeutic potential of adipose tissue-derived mesenchymal stem cells (AdSCs) in treatment of an acute colitis rat model using histological and molecular assessments. Thirty male Sprague Dawley acetic acid-induced (2 mL of 3%) acute colitis rat models were randomly divided into three equal groups of control receiving 0.5 mL/kg of normal saline, sulfasalazine group receiving 500 mg/kg sulfasalazine and AdSCs group transplanted transrectally with 2×106 MSCs. They were evaluated histologically and by real time PCR for expression of apoptotic genes until 21 days. MSCs were spindle shape and positive for osteogenic and adipogenic differentiation. They displayed mesenchymal and lacked hematopoietic markers. In control group, severe inflammation, edema, ulcer, necrosis and infiltration of leukocytes were noticed. In sulfasalazine group, a moderate inflammation, edema, ulcer, necrosis and infiltration of leukocytes were visible; and in AdSCs group, mild inflammation, congestion, and infiltration of leukocytes were observed with a mild edema, but necrosis was absent in colonic tissue. A stronger decrease in expression of Bax, together with a higher increase in Bcl-2 was noted in AdSCs group. Based on histological and molecular findings, AdSCs were effective to ameliorate colitis lesions through their anti-inflammatory and anti-apoptotic activities showing that transplantation of AdSCS can be a potentially useful strategy in treatment of colitis.

Author(s):  
Rasha Att ◽  
Angie Ameen ◽  
Horeya Korayem ◽  
Noha Abogresha ◽  
Yasser El-Wazir

IntroductionRegenerative treatment using stem cells represents a potentially effective therapy for cerebellar ataxia (CA). We compared the therapeutic potential of adipose tissue stem cells (ASCs) and bone marrow mesenchymal stem cells (BM-MSCs) in a rodent monosodium glutamate (MSG)-induced CA cell (BM-MSC) model.Material and methodsFemale Wistar rats (n = 40) were equally divided into a saline-treated control group and 3 MSG-induced CA groups randomly treated with either saline, or 1 × 106 ASCs or BM-MSCs. We assessed the following: 1) cerebellar motor functions in vivo (by Rotarod test, open-field test, and Quantitative gait analysis); 2) cerebellar histological architecture; and 3) cerebellar immunohistochemical examination of the Bax/Bcl-2 ratio as in indicator of apoptosis, and the levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) as neuroprotective factors.ResultsTreatment with either of the MSCs improved MSG-induced poor motor performance, restored the disrupted Purkinje cell layer, decreased neuronal apoptosis and enhanced cerebellar VEGF and IGF-1 levels observed in CA rats. Adipose tissue stem cells showed superiority over BM-MSCs in the improvement of some motor performance parameters and cerebellar VEGF and IGF-1 levels.ConclusionsIn conclusion, both stem cell types induced structural, physiological, and biochemical improvement, with ASCs being best for treatment of CA.


2021 ◽  
Vol 22 (3) ◽  
pp. 1375
Author(s):  
María Carmen Carceller ◽  
María Isabel Guillén ◽  
María Luisa Gil ◽  
María José Alcaraz

Adipose tissue represents an abundant source of mesenchymal stem cells (MSC) for therapeutic purposes. Previous studies have demonstrated the anti-inflammatory potential of adipose tissue-derived MSC (ASC). Extracellular vesicles (EV) present in the conditioned medium (CM) have been shown to mediate the cytoprotective effects of human ASC secretome. Nevertheless, the role of EV in the anti-inflammatory effects of mouse-derived ASC is not known. The current study has investigated the influence of mouse-derived ASC CM and its fractions on the response of mouse-derived peritoneal macrophages against lipopolysaccharide (LPS). CM and its soluble fraction reduced the release of pro-inflammatory cytokines, adenosine triphosphate and nitric oxide in stimulated cells. They also enhanced the migration of neutrophils or monocytes, in the absence or presence of LPS, respectively, which is likely related to the presence of chemokines, and reduced the phagocytic response. The anti-inflammatory effect of CM may be dependent on the regulation of toll-like receptor 4 expression and nuclear factor-κB activation. Our results demonstrate the anti-inflammatory effects of mouse-derived ASC secretome in mouse-derived peritoneal macrophages stimulated with LPS and show that they are not mediated by EV.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Shuang Liu ◽  
Minae Takahashi ◽  
Takeshi Kiyoi ◽  
Kensuke Toyama ◽  
Masaki Mogi

Calcium is a ubiquitous intracellular messenger that has a crucial role in determining the proliferation, differentiation, and functions of multipotent mesenchymal stem cells (MSCs). Our study is aimed at elucidating the influence of genetically manipulating Ca2+ release-activated Ca2+ (CRAC) channel-mediated intercellular Ca2+ signaling on the multipotency of MSCs. The abilities of genetically engineered MSCs, including CRAC-overexpressing and CRAC-knockout MSCs, to differentiate into multiple mesenchymal lineages, including adipogenic, osteogenic, and chondrogenic lineages, were evaluated. CRAC channel-mediated Ca2+ influx into these cells was regulated, and the differentiation fate of MSCs was modified. Upregulation of intracellular Ca2+ signals attenuated the adipogenic differentiation ability and slightly increased the osteogenic differentiation potency of MSCs, whereas downregulation of CRACM1 expression promoted chondrogenic differentiation potency. The findings demonstrated the effects of genetically manipulating MSCs by targeting CRACM1. CRAC-modified MSCs had distinct differentiation fates to adipocytes, osteoblasts, and chondrocytes. To aid in the clinical implementation of tissue engineering strategies for joint regeneration, these data may allow us to identify prospective factors for effective treatments and could maximize the therapeutic potential of MSC-based transplantation.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3410
Author(s):  
Seung-Cheol Lee ◽  
Yoo-Jung Lee ◽  
Inho Choi ◽  
Min Kim ◽  
Jung-Suk Sung

Adipocytes interact with adipose tissue macrophages (ATMs) that exist as a form of M2 macrophage in healthy adipose tissue and are polarized into M1 macrophages upon cellular stress. ATMs regulate adipose tissue inflammation by secreting cytokines, adipokines, and chemokines. CXC-motif receptor 6 (CXCR6) is the chemokine receptor and interactions with its specific ligand CXC-motif chemokine ligand 16 (CXCL16) modulate the migratory capacities of human adipose-derived mesenchymal stem cells (hADMSCs). CXCR6 is highly expressed on differentiated adipocytes that are non-migratory cells. To evaluate the underlying mechanisms of CXCR6 in adipocytes, THP-1 human monocytes that can be polarized into M1 or M2 macrophages were co-cultured with adipocytes. As results, expression levels of the M1 polarization-inducing factor were decreased, while those of the M2 polarization-inducing factor were significantly increased in differentiated adipocytes in a co-cultured environment with additional CXCL16 treatment. After CXCL16 treatment, the anti-inflammatory factors, including p38 MAPK ad ERK1/2, were upregulated, while the pro-inflammatory pathway mediated by Akt and NF-κB was downregulated in adipocytes in a co-cultured environment. These results revealed that the CXCL16/CXCR6 axis in adipocytes regulates M1 or M2 polarization and displays an immunosuppressive effect by modulating pro-inflammatory or anti-inflammatory pathways. Our results may provide an insight into a potential target as a regulator of the immune response via the CXCL16/CXCR6 axis in adipocytes.


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