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

Currently, the most effective therapy for liver diseases is liver transplantation, but its use is limited by organ donor shortage, economic reasons, and the requirement for lifelong immunosuppression. Mesenchymal stem cell (MSC) transplantation represents a promising alternative for treating liver pathologies in both human and veterinary medicine. Interestingly, these pathologies appear with a common clinical and pathological profile in the human and canine species; as a consequence, dogs may be a spontaneous model for clinical investigations in humans. The aim of this work was to characterize canine adipose-derived MSCs (cADSCs) and compare them to their human counterpart (hADSCs) in order to support the application of the canine model in cell-based therapy of liver diseases. Both cADSCs and hADSCs were successfully isolated from adipose tissue samples. The two cell populations shared a common fibroblast-like morphology, expression of stemness surface markers, and proliferation rate. When examining multilineage differentiation abilities, cADSCs showed lower adipogenic potential and higher osteogenic differentiation than human cells. Both cell populations retained high viability when kept in PBS at controlled temperature and up to 72 h, indicating the possibility of short-term storage and transportation. In addition, we evaluated the efficacy of autologous ADSCs transplantation in dogs with liver diseases. All animals exhibited significantly improved liver function, as evidenced by lower liver biomarkers levels measured after cells transplantation and evaluation of cytological specimens. These beneficial effects seem to be related to the immunomodulatory properties of stem cells. We therefore believe that such an approach could be a starting point for translating the results to the human clinical practice in future.

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The Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Atherosclerosis

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16999210128193549 ◽

2021 ◽

Vol 16 ◽

Author(s):

Vyacheslav Ogay ◽

Aliya Sekenova ◽

Yelena Li ◽

Assel Issabekova ◽

Arman Saparov

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Complex Disease ◽

Therapeutic Potential ◽

Circulatory System ◽

Promising Alternative ◽

Beneficial Effects ◽

Cell Based Therapy ◽

Multipotent Cells ◽

Potential Applications

Atherosclerosis is a multifactorial and complex disease involving the arterial intima of the circulatory system. The main risk factors of atherosclerosis are diabetes mellitus, hypertension, hyperlipidemic states, smoking, mental stress, unhealthy diet and a lack of physical activity. Recent studies have shown that dyslipidemia, inflammation and immune cells are involved in all stages of development of atherosclerosis. Mesenchymal stem cells are a heterogeneous subset of multipotent cells that can be isolated from nearly all human organs and tissues, and they possess both regenerative and immunomodulatory properties. Recent studies have shown that mesenchymal stem cells are able to provide immunosuppressive, regenerative and atheroprotective effects by reducing dyslipidemia, inflammation, and inhibiting endothelial cell dysfunction and plaque formation during the development of atherosclerosis in animal models. Based on these beneficial effects, mesenchymal stem cells are considered a promising alternative therapeutic approach for effective treatment of atherosclerosis. In this review, we summarize the current findings on potential applications of mesenchymal stem cells for preventing and regressing atherosclerosis as well as discuss strategies for improving the efficacy of mesenchymal stem cell-based therapy.

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Therapeutic Potential of Amniotic Fluid Derived Mesenchymal Stem Cells Based on their Differentiation Capacity and Immunomodulatory Properties

Current Stem Cell Research & Therapy ◽

10.2174/1574888x14666190222201749 ◽

2019 ◽

Vol 14 (4) ◽

pp. 327-336 ◽

Cited By ~ 9

Author(s):

Carl R. Harrell ◽

Marina Gazdic ◽

Crissy Fellabaum ◽

Nemanja Jovicic ◽

Valentin Djonov ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Animal Models ◽

Amniotic Fluid ◽

Therapeutic Potential ◽

Inflammatory Diseases ◽

Therapeutic Effects ◽

Differentiation Potential ◽

Differentiation Capacity ◽

Cell Based Therapy

Background: Amniotic Fluid Derived Mesenchymal Stem Cells (AF-MSCs) are adult, fibroblast- like, self-renewable, multipotent stem cells. During the last decade, the therapeutic potential of AF-MSCs, based on their huge differentiation capacity and immunomodulatory characteristics, has been extensively explored in animal models of degenerative and inflammatory diseases. Objective: In order to describe molecular mechanisms responsible for the therapeutic effects of AFMSCs, we summarized current knowledge about phenotype, differentiation potential and immunosuppressive properties of AF-MSCs. Methods: An extensive literature review was carried out in March 2018 across several databases (MEDLINE, EMBASE, Google Scholar), from 1990 to present. Keywords used in the selection were: “amniotic fluid derived mesenchymal stem cells”, “cell-therapy”, “degenerative diseases”, “inflammatory diseases”, “regeneration”, “immunosuppression”. Studies that emphasized molecular and cellular mechanisms responsible for AF-MSC-based therapy were analyzed in this review. Results: AF-MSCs have huge differentiation and immunosuppressive potential. AF-MSCs are capable of generating cells of mesodermal origin (chondrocytes, osteocytes and adipocytes), neural cells, hepatocytes, alveolar epithelial cells, insulin-producing cells, cardiomyocytes and germ cells. AF-MSCs, in juxtacrine or paracrine manner, regulate proliferation, activation and effector function of immune cells. Due to their huge differentiation capacity and immunosuppressive characteristic, transplantation of AFMSCs showed beneficent effects in animal models of degenerative and inflammatory diseases of nervous, respiratory, urogenital, cardiovascular and gastrointestinal system. Conclusion: Considering the fact that amniotic fluid is obtained through routine prenatal diagnosis, with minimal invasive procedure and without ethical concerns, AF-MSCs represents a valuable source for cell-based therapy of organ-specific or systemic degenerative and inflammatory diseases.

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Label-Free Rapid Separation and Enrichment of Bone Marrow-Derived Mesenchymal Stem Cells from a Heterogeneous Cell Mixture Using a Dielectrophoresis Device

Sensors ◽

10.3390/s18093007 ◽

2018 ◽

Vol 18 (9) ◽

pp. 3007 ◽

Cited By ~ 5

Author(s):

Junya Yoshioka ◽

Yu Ohsugi ◽

Toru Yoshitomi ◽

Tomoyuki Yasukawa ◽

Naoki Sasaki ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Gradient Method ◽

Label Free ◽

Rapid Separation ◽

Isolation System ◽

Tissue Samples ◽

Cell Based Therapy

Bone marrow-derived mesenchymal stem cells (BMSCs) are an important cell resource for stem cell-based therapy, which are generally isolated and enriched by the density-gradient method based on cell size and density after collection of tissue samples. Since this method has limitations with regards to purity and repeatability, development of alternative label-free methods for BMSC separation is desired. In the present study, rapid label-free separation and enrichment of BMSCs from a heterogeneous cell mixture with bone marrow-derived promyelocytes was successfully achieved using a dielectrophoresis (DEP) device comprising saw-shaped electrodes. Upon application of an electric field, HL-60 cells as models of promyelocytes aggregated and floated between the saw-shaped electrodes, while UE7T-13 cells as models of BMSCs were effectively captured on the tips of the saw-shaped electrodes. After washing out the HL-60 cells from the device selectively, the purity of the UE7T-13 cells was increased from 33% to 83.5% within 5 min. Although further experiments and optimization are required, these results show the potential of the DEP device as a label-free rapid cell isolation system yielding high purity for rare and precious cells such as BMSCs.

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Stem Cells from the Apical Papilla: A Promising Source for Stem Cell-Based Therapy

BioMed Research International ◽

10.1155/2019/6104738 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Jun Kang ◽

Wenguo Fan ◽

Qianyi Deng ◽

Hongwen He ◽

Fang Huang

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Current Knowledge ◽

Embryonic Stem ◽

Permanent Teeth ◽

Promising Alternative ◽

Dental Tissues ◽

Cell Based Therapy ◽

Apical Papilla ◽

Promising Source

Stem cells are biological cells that can self-renew and can differentiate into multiple cell lineages. Stem cell-based therapy is emerging as a promising alternative therapeutic option for various disorders. Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are isolated from various tissues and can be used as an alternative to embryonic stem cells. Stem cells from the apical papilla (SCAPs) are a novel population of MSCs residing in the apical papilla of immature permanent teeth. SCAPs present the characteristics of expression of MSCs markers, self-renewal, proliferation, migration, differentiation, and immunosuppression, which support the application of SCAPs in stem cell-based therapy, including the immunotherapy and the regeneration of dental tissues, bone, neural, and vascular tissues. In view of these properties and therapeutic potential, SCAPs can be considered as promising candidates for stem cell-based therapy. Thus the aim of our review was to summarize the current knowledge of SCAPs considering isolation, characterization, and multilineage differentiation. The prospects for their use in stem cell-based therapy were also discussed.

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SIRT1+ Adipose Derived Mesenchymal Stromal Stem Cells (ASCs) Suspended in Alginate Hydrogel for the Treatment of Subchondral Bone Cyst in Medial Femoral Condyle in the Horse. Clinical Report

Stem Cell Reviews and Reports ◽

10.1007/s12015-020-10025-6 ◽

2020 ◽

Vol 16 (6) ◽

pp. 1328-1334

Author(s):

Paweł Golonka ◽

Katarzyna Kornicka-Garbowska ◽

Krzysztof Marycz

Keyword(s):

Stem Cells ◽

Subchondral Bone ◽

Therapeutic Potential ◽

Bone Cyst ◽

Clinical Report ◽

Safe Procedure ◽

Alginate Hydrogel ◽

Cell Based Therapy ◽

First Choice ◽

Stromal Stem Cells

AbstractStem cell based therapy are now commonly applied in human and veterinary medical practice especially in orthopaedics. Mesenchymal stromal stem cells isolated from adipose tissue (ASC) are first choice option due to relatively non-invasive and safe procedure of tissue harvesting. However, ASC therapeutic potential strongly rely on patients general health condition, age and life-style. For that reason, to enhance therapeutic potential of cells, they are modified in vitro using different approaches. Previous studies have shown, that ASC treated with resveratrol, herein called SIRT+, are characterised by decreased senescence, increased proliferation rate and improved clinical outcome in autologous therapies. Herein, SIRT + cells in alginate hydrogel were applied to 5 years old warm breed mare was clinically evaluated due to the left hind lameness due to subchondral bone cyst. The therapeutic effect was assessed by the analysis of lameness score and radiological evaluation. This case report demonstrates the therapeutic potential of SIRT + cells in the treatment of orthopaedics disorders in horses as complete bone remodelling occurred after therapy and horse came back to training.

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Effect of mesenchymal stem cells combined with chondroitin sulfate in an osteoarthritis in vitro model

10.21203/rs.3.rs-23610/v2 ◽

2020 ◽

Author(s):

Saúl Pérez-Castrillo ◽

María Luisa González-Fernández ◽

Jessica Álvarez-Suárez ◽

Jaime Sánchez-Lázaro ◽

Marta Esteban-Blanco ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Chondroitin Sulfate ◽

Inflammatory Cytokines ◽

In Vitro Model ◽

Promising Alternative ◽

Cell Based Therapy ◽

Vitro Model ◽

Pro Inflammatory Cytokines

Abstract Introduction: Osteoarthritis (OA) is a degenerative joint disease which affects the whole joint structure. Many authors have focused on the factors responsible for the development of inflammatory processes involved in OA. Adipose tissue-derived mesenchymal stem cells (ASCs) represent a promising alternative of cell-based therapy strategy in the treatment of OA which could be combined with any other drug. Chondroitin sulfate plays a protective role in the joint based on the decrease of pro-inflammatory cytokines, thus having an important role in activating and inhibiting the metabolic pathways in chondrocytes. Aims: The effectiveness of chondroitin sulfate and ASCs combined in an in vitro model of OA has been evaluated in this study. Materials: Cytokines and factors which are involved in OA as well as specific cartilage gene expression after adding ASCs and chondroitin sulfate have been discussed in detail. Results: Our results show a decrease in the expression of all genes related to the pro-inflammatory cytokines analysed. Although there was no increase in the expression of the specific genes of the cartilage matrix, such as collagen type II and aggrecan. Conclusions: This study shows the effectiveness of association of ASCs and chondroitin sulfate for the treatment of OA.

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The Application of Induced Pluripotent Stem Cells Against Liver Diseases: An Update and a Review

Frontiers in Medicine ◽

10.3389/fmed.2021.644594 ◽

2021 ◽

Vol 8 ◽

Author(s):

Lei Zhang ◽

Ke Pu ◽

Xiaojun Liu ◽

Sarah Da Won Bae ◽

Romario Nguyen ◽

...

Keyword(s):

Stem Cells ◽

Liver Disease ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Liver Diseases ◽

Molecular Mechanisms ◽

Disease Modeling ◽

Health Concern ◽

Promising Alternative ◽

Induced Pluripotent

Liver diseases are a major health concern globally, and are associated with poor survival and prognosis of patients. This creates the need for patients to accept the main alternative treatment of liver transplantation to prevent progression to end-stage liver disease. Investigation of the molecular mechanisms underpinning complex liver diseases and their pathology is an emerging goal of stem cell scope. Human induced pluripotent stem cells (hiPSCs) derived from somatic cells are a promising alternative approach to the treatment of liver disease, and a prospective model for studying complex liver diseases. Here, we review hiPSC technology of cell reprogramming and differentiation, and discuss the potential application of hiPSC-derived liver cells, such as hepatocytes and cholangiocytes, in refractory liver-disease modeling and treatment, and drug screening and toxicity testing. We also consider hiPSC safety in clinical applications, based on genomic and epigenetic alterations, tumorigenicity, and immunogenicity.

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Engineered adipose-derived stem cells with IGF-1-modified mRNA ameliorates osteoarthritis development

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02695-x ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Haoyu Wu ◽

Zhi Peng ◽

Ying Xu ◽

Zixuan Sheng ◽

Yanshan Liu ◽

...

Keyword(s):

Stem Cells ◽

High Efficiency ◽

Therapeutic Potential ◽

Immunohistochemical Analysis ◽

Fluorescent Labeling ◽

Knee Joints ◽

Adipose Derived Stem Cells ◽

Promising Alternative

Abstract Background Osteoarthritis (OA), a prevalent degenerative disease characterized by degradation of extracellular matrix (ECM), still lacks effective disease-modifying therapy. Mesenchymal stem cells (MSCs) transplantation has been regarded as the most promising approach for OA treatment while engrafting cells alone might not be adequate for effective regeneration. Genetic modification has been used to optimize MSC-based therapy; however, there are still significant limitations that prevent the clinical translation of this therapy including low efficacy and safety concerns. Recently, chemically modified mRNA (modRNA) represents a promising alternative for the gene-enhanced MSC therapy. In this regard, we hypothesized that adipose derived stem cells (ADSCs) engineered with modRNA encoding insulin-like growth factor 1 (IGF-1) were superior to native ADSCs on ameliorating OA development. Methods Mouse ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IGF-1 modRNA engineered ADSCs (named as IGF-1-ADSCs) on chondrocytes. Finally, we evaluated the cell retention and chondroprotective effect of IGF-1-ADSCs in vivo using fluorescent labeling, histology and immunohistochemistry. Results modRNA transfected mouse ADSCs with high efficiency (85 ± 5%) and the IGF-1 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IGF-1 protein. In vitro, IGF-1-ADSCs induced increased anabolic markers expression of chondrocytes in inflammation environment compared to untreated ADSCs. In a murine OA model, histological and immunohistochemical analysis of knee joints harvested at 4 weeks and 8 weeks after OA induction suggested IGF-1-ADSCs had superior therapeutic effect over native ADSCs demonstrated by lower histological OARSI score and decreased loss of cartilage ECM. Conclusions These findings collectively supported the therapeutic potential of IGF-1-ADSCs for clinical OA management and cartilage repair.

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Mesenchymal Stem Cell-Derived Extracellular Vesicle: A Promising Alternative Therapy for Osteoporosis

International Journal of Molecular Sciences ◽

10.3390/ijms222312750 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12750

Author(s):

Cheng-Hsiu Lu ◽

Yi-An Chen ◽

Chien-Chih Ke ◽

Ren-Shyan Liu

Keyword(s):

Stem Cells ◽

Therapeutic Potential ◽

Large Population ◽

Alternative Therapy ◽

Osteoporosis Treatment ◽

Extracellular Vesicle ◽

Therapeutic Effects ◽

Promising Alternative ◽

Treatment Of Osteoporosis ◽

Therapeutic Applications

Osteoporosis is the chronic metabolic bone disease caused by the disturbance of bone remodeling due to the imbalance of osteogenesis and osteoclastogenesis. A large population suffers from osteoporosis, and most of them are postmenopausal women or older people. To date, bisphosphonates are the main therapeutic agents in the treatment of osteoporosis. However, limited therapeutic effects with diverse side effects caused by bisphosphonates hindered the therapeutic applications and decreased the quality of life. Therefore, an alternative therapy for osteoporosis is still needed. Stem cells, especially mesenchymal stem cells, have been shown as a promising medication for numerous human diseases including many refractory diseases. Recently, researchers found that the extracellular vesicles derived from these stem cells possessed the similar therapeutic potential to that of parental cells. To date, a number of studies demonstrated the therapeutic applications of exogenous MSC-EVs for the treatment of osteoporosis. In this article, we reviewed the basic back ground of EVs, the cargo and therapeutic potential of MSC-EVs, and strategies of engineering of MSC-EVs for osteoporosis treatment.

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The Anti-fibrotic Effect of Human Fetal Skin-derived Stem Cell Secretome on the Liver Fibrosis

10.21203/rs.3.rs-39850/v1 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Causes Of Mortality ◽

Smad7 Expression

Abstract Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages.Methods: In this study, we investigated the effect ofhuman fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCssecretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCssecretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCssecretome in hepatic stellate cells (HSCs).Results: Our results showed that hFFSCssecretomeffectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found thathFFSCssecretom reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSCsecretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression.Conclusions: In conclusions, our results suggest that hFFSCssecretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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