scholarly journals The Application of Mesenchymal Stem Cells in the Treatment of Liver Diseases: Mechanism, Efficacy, and Safety Issues

2021 ◽  
Vol 8 ◽  
Author(s):  
Ya Yang ◽  
Yalei Zhao ◽  
Lingjian Zhang ◽  
Fen Zhang ◽  
Lanjuan Li
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Immune Regulation ◽  
Liver Diseases ◽  
Efficacy And Safety ◽  
Safety Issues ◽  
Novel Treatment ◽  
Significant Efficacy

Mesenchymal stem cell (MSC) transplantation is a novel treatment for liver diseases due to the roles of MSCs in regeneration, fibrosis inhibition and immune regulation. However, the mechanisms are still not completely understood. Despite the significant efficacy of MSC therapy in animal models and preliminary clinical trials, issues remain. The efficacy and safety of MSC-based therapy in the treatment of liver diseases remains a challenging issue that requires more investigation. This article reviews recent studies on the mechanisms of MSCs in liver diseases and the associated challenges and suggests potential future applications.

scholarly journals Application of Modified Mesenchymal Stem Cells Transplantation in the Treatment of Liver Injury

2021 ◽  
pp. 327-343
Author(s):  
L LIU ◽  
F YANG
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immune Regulation ◽  
Liver Diseases ◽  
Mesenchymal Stem Cell Transplantation

Acute and chronic hepatitis, cirrhosis, and other liver diseases pose a serious threat to human health; however, liver transplantation is the only reliable treatment for the terminal stage of liver diseases. Previous researchers have shown that mesenchymal stem cells (MSCs) are characterized by differentiation and paracrine effects, as well as anti-oxidative stress and immune regulation functions. When MSCs are transplanted into animals, they migrate to the injured liver tissue along with the circulation, to protect the liver and alleviate the injury through the paracrine, immune regulation and other characteristics, making mesenchymal stem cell transplantation a promising alternative therapy for liver diseases. Although the efficacy of MSCs transplantation has been confirmed in various animal models of liver injury, many researchers have also proposed various pretreatment methods to improve the efficacy of mesenchymal stem cell transplantation, but there is still lack a set of scientific methods system aimed at improving the efficacy of transplantation therapy in scientific research and clinical practice. In this review, we summarize the possible mechanisms of MSCs therapy and compare the existing methods of MSCs modification corresponding to the treatment mechanism, hoping to provide as a reference to help future researchers explore a safe and simple transplantation strategy.

Enhancing therapeutic effects and in vivo tracking of adipose tissue derived mesenchymal stem cells for liver injury using bioorthogonal click chemistry

Nanoscale ◽  
2020 ◽  
Author(s):  
Naishun Liao ◽  
Da Zhang ◽  
Ming Wu ◽  
Huang-Hao Yang ◽  
Xiaolong Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Liver Injury ◽  
Mesenchymal Stem Cell ◽  
Liver Diseases ◽  
Therapeutic Effects

Adipose tissue derived mesenchymal stem cell (ADSC)-based therapy is attractive for liver diseases, but the long-term therapeutic outcome is still far from satisfaction due to low hepatic engraftment efficiency of...

scholarly journals Journey of Mesenchymal Stem Cells for Homing: Strategies to Enhance Efficacy and Safety of Stem Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Keun Kang ◽  
Il Seob Shin ◽  
Myung Soon Ko ◽  
Jung Youn Jo ◽  
Jeong Chan Ra
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Human Mesenchymal Stem Cells ◽  
Cellular Damage ◽  
Efficacy And Safety ◽  
Clinical Benefits

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and thein vivoenvironment facilitate and are required for the migration of MSCs to the site of insult or injuryin vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.

scholarly journals Transplantation of Mesenchymal Stem Cells in Treating Patients with Severe COVID-19: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 5 (3) ◽  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Bibliographic Databases ◽  
Human Mscs ◽  
Medical Subject Headings ◽  
Human Organ ◽  
Mesenchymal Stem Cell Transplantation ◽  
Meeting Abstract

The objective of the study is to perform a critical review, exploration, and strong summary of the roles of mesenchymal stem cell transplantation in treating various diseases, including COVID-19. A comprehensive search was carried out in mainstream bibliographic databases or Medical Subject Headings, including Scien Direct, PubMed, Scopus, ISI Web of Science, and websites of the news. The search was applied to the articles that were published between January 2020 and April 2020. Needed article information was extracted from each article by : 1) direct information including journal (research article, review article, meeting abstract, conference abstract, correspondence, author index, editorial board meeting abstract, discussion), book chapter, title, authors, abstract, full text documents of candidate studies, websites of the news, publishing year; 2) study period; 3) research (study) method used; 4) types of mesenchymal stem cells; and 5) types of human organ system disorder or disease studied. With strict literature search and screening processes, it yielded 6 articles from 76 articles of initial literature databases and websites of the news (January 2020 to April 2020). Anti-inflammatory and immunomodulatory properties of MSCs in the treatment of respiratory diseases were confirmed by at least 17 clinical studies and more than 70 clinical trials are registered in this issue that are available at: https:// www.clinicaltrials.gov. MSC transplantation improves the treatment outcome of COVID-19 patients may be due to controlling inflammatory response and promoting tissue regeneration and repair. In conclusion, Human MSCs are currently being evaluated as a stem cell treatment for a number of diseases, particularly severe COVID-19 and have been demonstrated to be safe in clinical trials. There are some promising reports to apply MSCs therapy to treat COVID-19. MSCs may possibly be one of the most ideal therapeutics, or a combination of treatment to treat patients with COVID-19. Nevertheless, further studies are urgently needed to investigate and optimize a number of variables in the human MSC culture environment by developing a bioprocess that can be operated in accordance with the Good Manufacturing Product (GMP).

scholarly journals Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Atsunori Tsuchiya ◽  
Yuichi Kojima ◽  
Shunzo Ikarashi ◽  
Satoshi Seino ◽  
Yusuke Watanabe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Bowel Diseases ◽  
Liver Diseases ◽  
Bowel Diseases ◽  
Inflammatory Bowel

scholarly journals Efficacy and Safety of Mesenchymal Stem Cells Co-Infusion in Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Teng li ◽  
Chengxin Luo ◽  
Jiasi Zhang ◽  
Ling Wei ◽  
Wei Sun ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Lower Risk ◽  
Meta Analysis ◽  
Current Evidence ◽  
Efficacy And Safety

Abstract BackgroundHematopoietic stem cell transplantation (HSCT) is a life-saving strategy for severe hematological conditions, but its efficacy and safety need further improvement. Co-infusion of mesenchymal stem cells (MSCs) may bring promise for the overall efficacy in HSCT setting. About that there are increasing studies, while the results from different trials are conflicting. A systematic review and meta-analysis are needed to appraise the real efficacy of MSCs co-infusion in HSCT. MethodsFive medical databases were searched to identify related controlled studies, which included individuals with hematological diseases receiving allogeneic HSCT (allo-HSCT), and with MSCs co-infusion as intervention arm versus no MSCs as comparison arm. Meta-analysis was performed using RevMan 5.4.ResultsUltimately, 19 trials met the inclusion criteria. MSCs co-infusion was associated with shorter time both to ANC engraftment (4RCTs: SMD -1.20, p = 0.04; 10nRCTs: SMD -0.54, p = 0.04) and PLT engraftment (4RCTs: SMD -0.60, p = 0.04; 10nRCTs: SMD -0.70, p = 0.01), lower risk of cGVHD incidence (4RCTs: RR 0.53, p = 0.01; 10nRCTs: RR 0.50, p < 0.01), and slightly positive trend towards the risk of aGVHD incidence (3RCTs: RR 0.84, p = 0.33; 9nRCTs: RR 0.74, p < 0.01) and NRM(3RCTs: OR 0.59, p = 0.34; 3nRCTs: OR 0.18, p < 0.01); didn’t affect relapse (5RCTs: RR 1.34, p = 0.34; 4nRCTs: RR 0.74, p = 0.24) and overall survival (4RCTs: HR 1.54, p = 0.18; 6nRCTs: HR 0.60, p = 0.06). Subgroup analyses revealed that, when co-transplanted with MSCs, patients younger than 18 or those received HLA-haploidentical grafts had improved engraftment (ANC and PLT）and lower risk of NRM and GVHD (acute and chronic forms) incidence. For adults or those received HLA-identical grafts, the risk of cGVHD incidence were reduced. Patients with hematologic malignancies had lower risk of developing GVHD and NRM, patients with non-malignancies showed faster engraftment.ConclusionWithout increasing the risk of mortality or relapse, MSCs co-infusion in allo-HSCT improved engraftment of platelet and neutrophil, reduced the risk of developing cGVHD. In terms of aGVHD and NRM, the effect of MSCs co-infusion was not quite significant with current evidence.

Abstract 16769: Intravenous Injection of Neonatal Cardiac Mesenchymal Stem Cells is a Viable Alternative Route to Treat Acute Myocardial Infarction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Progyaparamita Saha ◽  
Rachana Mishra ◽  
Sudhish Sharma ◽  
Aakash Shah ◽  
Lauren Davidson ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Placebo Group ◽  
Randomized Clinical Trials ◽  
Brown Norway ◽  
Male Rat ◽  
Myocardial Infraction

Introduction: Cardiovascular disease is major cause of morbidity and mortality around the world and major health care burden indeed. Ischemic heart disease (IHD) and myocardial ischemia (MI) are most devastating cardiovascular disease. Multiple stem cell/ cardiac progenitor cell therapy has been reported previously to treat cardiovascular disease safely. However randomized clinical trials with adult cardiac progenitor cells or cardiosphere-derived cells unable to show long-term efficacy. We have our unique source of human neonatal cardiac tissue derived neonatal cardiac mesenchymal stem cells (nMSCs). Systemic administration is preferred route of stem cell delivery in order to consecutive dosage for most of the clinical trials. We hypothesized that nMSCs have unique proteome profile, which supports their survival, migration and homing. They home to the injured myocardium when administered intravenously (IV) to a wild type male rat subjected to MI. Methods: This model was created in 6-week-old Brown-Norway Rats. Rats were subjected to an anterior myocardial Infraction (MI) by permanent LAD ligation. The rats were treated with nMSCs (1^10 6 cells/Kg, 5^10 6 cells/Kg and 10^10 6 cells/Kg) along with placebo and sham, which are delivered intravenously by tail vein injection. Rats are once again treated with nMSCs/placebo 4 days after MI. Baseline echocardiography is performed 24 hours after MI. Results: LVEF was significantly higher in the nMSC-treated group than in the placebo group. Other parameters, including fractional shortening (FS) and decreased end-systolic volume (ESV), were also significantly improved when compared with the placebo group, and other LV functional parameter, including cardiac output/body weight and posterior wall thickness tended towards improvement of remodeled heart. Conclusions: Twice intravenous administration of nMSCs for MI attenuate the progressive deterioration of left ventricle and adverse remodeling of rat heart.

Stem Cell Therapy: A Promising Approach in Treatment of COVID 19

2020 ◽  
Vol 15 ◽  
Author(s):  
Bahareh Abbaspanah ◽  
Saeid Abroun ◽  
Morteza Zarrabi ◽  
Ashkan Mozdgir ◽  
Mohammad Mollanouri
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Global Health ◽  
Clinical Outcome ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Antiviral Treatment ◽  
Health Crisis

: COVID-19 pandemic is a global health crisis in the 21st Century. There are currently no approved vaccine and no particular antiviral treatment for coronavirus disease. As COVID-19 has had a broad range of illnesses, it is necessary to find a safe and effective therapeutic method for COVID-19. An attractive approach for treating COVID-19 is cell therapy. Cell therapy aims to inject new and healthy stem cells into a patient’s body, to repair the damaged cells and tissues. Stem cell therapy is one of the most studied and important approaches in treatment of COVID-19 these days. The significant clinical outcome was observed by the adoptive transfer of stem cells, specifically mesenchymal stem cells. This study reviews the characteristics of stem cells and clinical trials which uses stem cells in treating COVID-19.

scholarly journals Advances in the understanding of poor graft function following allogeneic hematopoietic stem-cell transplantation

2020 ◽  
Vol 11 ◽  
pp. 204062072094874
Author(s):  
Juan Chen ◽  
Hongtao Wang ◽  
Jiaxi Zhou ◽  
Sizhou Feng
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Function ◽  
Hematopoietic Stem ◽  
Poor Graft Function

Poor graft function (PGF) following allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is a life-threatening complication and is characterized by bilineage or trilineage blood cell deficiency and hypoplastic marrow with full chimerism. With the rapid development of allo-HSCT, especially haploidentical-HSCT, PGF has become a growing concern. The most common risk factors illustrated by recent studies include low dose of infused CD34+ cells, donor-specific antibody, cytomegalovirus infection, graft versus host disease (GVHD), iron overload and splenomegaly, among others. Because of the poor prognosis of PGF, it is crucial to uncover the underlying mechanism, which remains elusive. Recent studies have suggested that the bone marrow microenvironment may play an important role in the pathogenesis of PGF. Deficiency and dysfunction of endothelial cells and mesenchymal stem cells, elevated reactive oxygen species (ROS) levels, and immune abnormalities are believed to contribute to PGF. In this review, we also discuss recent clinical trials that evaluate the safety and efficacy of new strategies in patients with PGF. CD34+-selected stem-cell boost (SCB) is effective with an acceptable incidence of GVHD, despite the need for a second donation. Alternative strategies including the applications of mesenchymal stem cells, N-acetyl-l-cysteine (NAC), and eltrombopag have shown favorable outcomes, but further large-scale studies are needed due to the small sample sizes of the recent clinical trials.

scholarly journals Subconjunctival injection of mesenchymal stem cells for corneal failure due to limbal stem cell deficiency: state of the art

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sara Galindo ◽  
Ana de la Mata ◽  
Marina López-Paniagua ◽  
Jose M. Herreras ◽  
Inmaculada Pérez ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Minimally Invasive ◽  
Corneal Opacity ◽  
Experimental Models ◽  
Subconjunctival Injection ◽  
Ocular Surface Diseases ◽  
Limbal Stem Cell

AbstractMesenchymal stem cells (MSCs) have unique and beneficial properties and are currently used to treat a broad variety of diseases. These properties include the potential for differentiation into other cell types, secretion of different trophic factors that promote a regenerative microenvironment, anti-inflammatory actions, selective migration to damaged tissues, and non-immunogenicity. MSCs are effective for the treatment of ocular surface diseases such as dry eye, corneal burns, and limbal stem cell deficiency (LSCD), both in experimental models and in humans. LSCD is a pathological condition in which damage occurs to the limbal epithelial stem cells, or their niche, that are responsible for the continuous regeneration of the corneal epithelium. If LSCD is extensive and/or severe, it usually causes corneal epithelial defects, ulceration, and conjunctival overgrowth of the cornea. These changes can result in neovascularization and corneal opacity, severe inflammation, pain, and visual loss. The effectiveness of MSCs to reduce corneal opacity, neovascularization, and inflammation has been widely studied in different experimental models of LSCD and in some clinical trials; however, the methodological disparity used in the different studies makes it hard to compare outcomes among them. In this regard, the MSC route of administration used to treat LSCD and other ocular surface diseases is an important factor. It should be efficient, minimally invasive, and safe. So far, intravenous and intraperitoneal injections, topical administration, and MSC transplantation using carrier substrata like amniotic membrane (AM), fibrin, or synthetic biopolymers have been the most commonly used administration routes in experimental models. However, systemic administration carries the risk of potential side effects and transplantation requires surgical procedures that could complicate the process. Alternatively, subconjunctival injection is a minimally invasive and straightforward technique frequently used in ophthalmology. It enables performance of local treatments using high cell doses. In this review, we provide an overview of the current status of MSC administration by subconjunctival injection, analyzing the convenience, safety, and efficacy for treatment of corneal failure due to LSCD in different experimental models. We also provide a summary of the clinical trials that have been completed, are in progress, or being planned.

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