scholarly journals Regenerative Potential of Mesenchymal Stem Cells’ (MSCs) Secretome for Liver Fibrosis Therapies

2021 ◽  
Vol 22 (24) ◽  
pp. 13292
Author(s):  
Simona-Rebeca Nazarie (Ignat) ◽  
Sami Gharbia ◽  
Anca Hermenean ◽  
Sorina Dinescu ◽  
Marieta Costache
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Critical Conditions ◽  
Therapeutic Role ◽  
Cell Therapies ◽  
Liver Injuries ◽  
Attractive Option ◽  
A Cell ◽  
End Stage

Chronic liver injuries lead to liver fibrosis and then to end-stage liver cirrhosis. Liver transplantation is often needed as a course of treatment for patients in critical conditions, but limitations associated with transplantation prompted the continuous search for alternative therapeutic strategies. Cell therapy with stem cells has emerged as an attractive option in order to stimulate tissue regeneration and liver repair. Transplanted mesenchymal stem cells (MSCs) could trans-differentiate into hepatocyte-like cells and, moreover, show anti-fibrotic and immunomodulatory effects. However, cell transplantation may lead to some uncontrolled side effects, risks associated with tumorigenesis, and cell rejection. MSCs’ secretome includes a large number of soluble factors and extracellular vesicles (EVs), through which they exert their therapeutic role. This could represent a cell-free strategy, which is safer and more effective than MSC transplantation. In this review, we focus on cell therapies based on MSCs and how the MSCs’ secretome impacts the mechanisms associated with liver diseases. Moreover, we discuss the important therapeutic role of EVs and how their properties could be further used in liver regeneration.

scholarly journals Nanocurcumin Improves the Therapeutic Role of Mesenchymal Stem Cells in Liver Fibrosis Rats

2021 ◽  
Vol 11 (6) ◽  
pp. 14463-14479
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Agent ◽  
Albino Rats ◽  
Therapeutic Role ◽  
Recovery Group ◽  
Wistar Albino Rats ◽  
Promising Therapeutic Agent

Nano-curcumin (Nano-Cur) is a promising therapeutic agent that has a wide array of effective medicinal potentials. Therefore, the present inquiry aimed to assess Nano-Cur's impact on the therapeutic effect of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in the rat model of liver fibrosis prompted by carbon tetrachloride (CCl4). Liver fibrosis was developed in 30male Wistar albino rats which were divided into five groups, six animals each. The 1st group (CCl4 group) was sacrificed immediately after the induction of liver fibrosis. The 2nd group received a single iv injection of BM-MSCs and left for 4weeks, the3rd group received 100mg/kg b.w. Nano-Cur 3times/week for 4weeks, the 4th group received a single iv injection of 107 BM-MSCs accompanied with Nano-Cur 3times/week for 4weeks, and the 5th group left for 4weeks without any intervention. Data revealed that treatment with BM-MSCs plus Nano-Cur alleviated liver fibrosis through reducing liver oxidative stress and restoring both liver histological picture and enzymatic profile. Additionally, companied treatment resulted in reducing TGFβ1 levels and attenuating the expression of Smad 2,3 and collagen I, III genes. Conversely, most of the pathological lesions were still detected in the recovery group. Nano-Cur improves the therapeutic role of BM-MSCs in liver fibrosis rats.

scholarly journals Heterogenic transplantation of bone marrow-derived rhesus macaque mesenchymal stem cells ameliorates liver fibrosis induced by carbon tetrachloride in mouse

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4336 ◽  
Author(s):  
Xufeng Fu ◽  
Bin Jiang ◽  
Bingrong Zheng ◽  
Yaping Yan ◽  
Junfeng Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Carbon Tetrachloride ◽  
Liver Fibrosis ◽  
Liver Diseases ◽  
Pathological Examination ◽  
Paracrine Effects ◽  
End Stage

Liver fibrosis is a disease that causes high morbidity and has become a major health problem. Liver fibrosis can lead to the end stage of liver diseases (livercirrhosisand hepatocellularcarcinoma). Currently, liver transplantation is the only effective treatment for end-stage liver disease. However, the shortage of organ donors, high cost of medical surgery, immunological rejection and transplantation complications severely hamper liver transplantation therapy. Mesenchymal stem cells (MSCs) have been regarded as promising cells for clinical applications in stem cell therapy in the treatment of liver diseases due to their unique multipotent differentiation capacity, immunoregulation and paracrine effects. Although liver fibrosis improvements by MSC transplantation in preclinical experiments as well as clinical trials have been reported, the in vivo fate of MSCs after transportation and their therapeutic mechanisms remain unclear. In this present study, we isolated MSCs from the bone marrow of rhesus macaques. The cells exhibited typical MSC markers and could differentiate into chondrocytes, osteocytes, and adipocytes, which were not affected by labeling with enhanced green fluorescent protein (EGFP). The harvested MSCs respond to interferon-γ stimulation and have the ability to inhibit lymphocyte proliferation in vitro. EGFP-labeled MSCs (1 × 106 cells) were transplanted into mice with carbon tetrachloride-induced liver fibrosis via tail vein injection. The ability of the heterogenic MSC infusion to ameliorate liver fibrosis in mice was evaluated by a blood plasma chemistry index, pathological examination and liver fibrosis-associated gene expression. Additionally, a small number of MSCs that homed and engrafted in the mouse liver tissues were evaluated by immunofluorescence analysis. Our results showed that the transplantation of heterogenic MSCs derived from monkey bone marrow can be used to treat liver fibrosis in the mouse model and that the paracrine effects of MSCs may play an important role in the improvement of liver fibrosis.

Differentiation of mesenchymal stem cells from humans and animals into insulin-producing cells: An overview in vitro induction forms

2020 ◽  
Vol 16 ◽  
Author(s):  
Bruna O. S. Câmara ◽  
Bruno M. Bertassoli ◽  
Natália M. Ocarino ◽  
Rogéria Serakides
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Adipogenic Differentiation ◽  
Medium Composition ◽  
Cell Therapies ◽  
Insulin Producing Cells ◽  
Msc Differentiation

The use of stem cells in cell therapies has shown promising results in the treatment of several diseases, including diabetes mellitus, in both humans and animals. Mesenchymal stem cells (MSCs) can be isolated from various locations, including bone marrow, adipose tissues, synovia, muscles, dental pulp, umbilical cords, and the placenta. In vitro, by manipulating the composition of the culture medium or transfection, MSCs can differentiate into several cell lineages, including insulin-producing cells (IPCs). Unlike osteogenic, chondrogenic, and adipogenic differentiation, for which the culture medium and time are similar between studies, studies involving the induction of MSC differentiation in IPCs differ greatly. This divergence is usually evident in relation to the differentiation technique used, the composition of the culture medium, the cultivation time, which can vary from a few hours to several months, and the number of steps to complete differentiation. However, although there is no “gold standard” differentiation medium composition, most prominent studies mention the use of nicotinamide, exedin-4, ß-mercaptoethanol, fibroblast growth factor b (FGFb), and glucose in the culture medium to promote the differentiation of MSCs into IPCs. Therefore, the purpose of this review is to investigate the stages of MSC differentiation into IPCs both in vivo and in vitro, as well as address differentiation techniques and molecular actions and mechanisms by which some substances, such as nicotinamide, exedin-4, ßmercaptoethanol, FGFb, and glucose, participate in the differentiation process.

scholarly journals Electrospun fibers enhanced the paracrine signaling of mesenchymal stem cells for cartilage regeneration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nurul Dinah Kadir ◽  
Zheng Yang ◽  
Afizah Hassan ◽  
Vinitha Denslin ◽  
Eng Hin Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Electrospun Fiber ◽  
Cartilage Regeneration ◽  
Conditioned Media ◽  
Biologically Active ◽  
Paracrine Signaling ◽  
Therapeutic Value ◽  
A Cell ◽  
Fiber Sheet

Abstract Background Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments. These biologically active factors exert an impact on the surrounding cells, eliciting regenerative responses that create an opportunity for exploiting MSCs towards a cell-free therapy for cartilage regeneration. The conventional method of culturing MSCs on a tissue culture plate (TCP) does not provide the physiological microenvironment for optimum secretome production. In this study, we explored the potential of electrospun fiber sheets with specific orientation in influencing the MSC secretome production and its therapeutic value in repairing cartilage. Methods Conditioned media (CM) were generated from MSCs cultured either on TCP or electrospun fiber sheets of distinct aligned or random fiber orientation. The paracrine potential of CM in affecting chondrogenic differentiation, migration, proliferation, inflammatory modulation, and survival of MSCs and chondrocytes was assessed. The involvement of FAK and ERK mechanotransduction pathways in modulating MSC secretome were also investigated. Results We showed that conditioned media of MSCs cultured on electrospun fiber sheets compared to that generated from TCP have improved secretome yield and profile, which enhanced the migration and proliferation of MSCs and chondrocytes, promoted MSC chondrogenesis, mitigated inflammation in both MSCs and chondrocytes, as well as protected chondrocytes from apoptosis. Amongst the fiber sheet-generated CM, aligned fiber-generated CM (ACM) was better at promoting cell proliferation and augmenting MSC chondrogenesis, while randomly oriented fiber-generated CM (RCM) was more efficient in mitigating the inflammation assault. FAK and ERK signalings were shown to participate in the modulation of MSC morphology and its secretome production. Conclusions This study demonstrates topographical-dependent MSC paracrine activities and the potential of employing electrospun fiber sheets to improve the MSC secretome for cartilage regeneration.

scholarly journals Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice

2018 ◽  
Vol 8 (3) ◽  
pp. 271-284 ◽  
Author(s):  
Yusuke Watanabe ◽  
Atsunori Tsuchiya ◽  
Satoshi Seino ◽  
Yuzo Kawata ◽  
Yuichi Kojima ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis

Integrin β1 activation by micro-scale curvature promotes pro-angiogenic secretion of human mesenchymal stem cells

2017 ◽  
Vol 5 (35) ◽  
pp. 7415-7425 ◽  
Author(s):  
Zhengdong Li ◽  
Weiwei Wang ◽  
Xun Xu ◽  
Karl Kratz ◽  
Jie Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Β1 Integrin ◽  
Integrin Β1 ◽  
Micro Scale ◽  
Culture Substrate ◽  
A Cell ◽  
Scale Surface ◽  
Cell Culture Substrate

A cell culture substrate with micro-scale surface curvature promotes β1 integrin activation and pro-angiogenic secretion of mesenchymal stem cells.

scholarly journals Human placental mesenchymal stem cells ameliorate liver fibrosis in mice by upregulation of Caveolin1 in hepatic stellate cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunqi Yao ◽  
Zhemin Xia ◽  
Fuyi Cheng ◽  
Qingyuan Jang ◽  
Jiao He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Therapeutic Effect ◽  
Hepatic Stellate Cells ◽  
Time Window ◽  
Stellate Cells ◽  
Therapeutic Benefits ◽  
Placental Mesenchymal Stem Cells

Abstract Background Liver fibrosis (LF) is a common pathological process characterized by the activation of hepatic stellate cells (HSCs) and accumulation of extracellular matrix. Severe LF causes cirrhosis and even liver failure, a major cause of morbidity and mortality worldwide. Transplantation of human placental mesenchymal stem cells (hPMSCs) has been considered as an alternative therapy. However, the underlying mechanisms and the appropriate time window for hPMSC transplantation are not well understood. Methods We established mouse models of CCl4-injured LF and administered hPMSCs at different stages of LF once a week for 2 weeks. The therapeutic effect of hPMSCs on LF was investigated, according to histopathological and blood biochemical analyses. In vitro, the effect of hPMSCs and the secretomes of hPMSCs on the inhibition of activated HSCs was assessed. RNA sequencing (RNA-seq) analysis, real-time PCR array, and western blot were performed to explore possible signaling pathways involved in treatment of LF with hPMSCs. Results hPMSC treatment notably alleviates experimental hepatic fibrosis, restores liver function, and inhibits inflammation. Furthermore, the therapeutic effect of hPMSCs against mild-to-moderate LF was significantly greater than against severe LF. In vitro, we observed that the hPMSCs as well as the secretomes of hPMSCs were able to decrease the activation of HSCs. Mechanistic dissection studies showed that hPMSC treatment downregulated the expression of fibrosis-related genes, and this was accompanied by the upregulation of Caveolin-1 (Cav1) (p < 0.001). This suggested that the amelioration of LF occurred partly due to the restoration of Cav1 expression in activated HSCs. Upregulation of Cav1 can inhibit the TGF-β/Smad signaling pathway, mainly by reducing Smad2 phosphorylation, resulting in the inhibition of activated HSCs, whereas this effect could be abated if Cav1 was silenced in advance by siRNAs. Conclusions Our findings suggest that hPMSCs could provide multifaceted therapeutic benefits for the treatment of LF, and the TGF-β/Cav1 pathway might act as a therapeutic target for hPMSCs in the treatment of LF.

scholarly journals The Art of Mesenchymal Stem Cells in Liver Fibrosis Management

2021 ◽  
Vol 3 (2) ◽  
pp. 15-24
Author(s):  
Farid Amansyah ◽  
Dito Anurogo
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Tissue Damage ◽  
Fundamental Concept ◽  
Scientific Review ◽  
Safety And Efficacy ◽  
Experimental Animals

Liver fibrogenesisis chronic tissue damage characterized by an extracellular ac-cumulation of fibrillar matrix associated with continuous degradation and remod-elling. This scientific review describes current concepts on the pathophysiology of liver fibrosis, inflammation asa fundamental concept of liver fibrosis, mechanistic concepts of liver fibrosis, the role of mesenchymal stem cells (MSC) in liver injury, the functional effects of MSC secretome, the advantages of secretome ther-apy, and the latest research developments on MSC. The role of MSCs has been proven in many liver fibrosis studies involving experimental animals. However, it still requires further research for safety and efficacy aspects.

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