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.

scholarly journals Comparative characterization and osteogenic / adipogenic differentiation of mesenchymal stem cells derived from male rat hair follicles and bone marrow

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Abdel Kader A. Zaki ◽  
Tariq I. Almundarij ◽  
Faten A. M. Abo-Aziza
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Adipogenic Differentiation ◽  
Adult Stem Cell ◽  
Cell Counting ◽  
Population Doubling ◽  
Male Rat ◽  
Cell Source

AbstractClinical applications of cell therapy and tissue regeneration under different conditions need a multiplicity of adult stem cell sources. Up to date, little is available on the comparative isolation, characterization, proliferation, rapid amplification, and osteogenic/adipogenic differentiation of rat mesenchymal stem cells (MSCs) isolated from living bulge cells of the hair follicle (HF) and bone marrow (BM) from the same animal. This work hopes to use HF-MSCs as an additional adult stem cell source for research and application. After reaching 80% confluence, the cell counting, viability %, and yields of HF-MSCs and BM-MSCs were nearly similar. The viability % was 91.41 ± 2.98 and 93.11 ± 3.06 while the cells yield of initial seeding was 33.15 ± 2.76 and 34.22 ± 3.99 and of second passage was 28.76 ± 1.01 and 29.56 ± 3.11 for HF-MSCs and BM-MSCs respectively. Clusters of differentiation (CDs) analysis revealed that HF-MSCs were positively expressed CD34, CD73 and CD200 and negatively expressed CD45. BM-MSCs were positively expressed CD73 and CD200 and negatively expressed of CD34 and CD45. The proliferation of HF-MSCs and BM-MSCs was determined by means of incorporation of Brd-U, population doubling time (PDT) assays and the quantity of formazan release. The percentage of Brd-U positive cells and PDT were relatively similar in both types of cells. The proliferation, as expressed by the quantity of formazan assay in confluent cells, revealed that the quantity of release by BM-MSCs was slightly higher than HF-MSCs. Adipogenic differentiated BM-MSCs showed moderate accumulation of oil red-O stained lipid droplets when compared to that of HF-MSCs which exhibited high stain. The total lipid concentration was significantly higher in adipogenic differentiated HF-MSCs than BM-MSCs (P < 0.05). It was found that activity of bone alkaline phosphatase and calcium concentration were significantly higher (P < 0.01 and P < 0.05 respectively) in osteogenic differentiated BM-MSCs than that of HF-MSCs. The present findings demonstrate that the HF-MSCs are very similar in most tested characteristics to BM-MSCs with the exception of differentiation. Additionally; no issues have been reported during the collection of HF-MSCs. Therefore, the HF may represent a suitable and accessible source for adult stem cells and can be considered an ideal cell source for adipogenesis research.

scholarly journals Rebuilding the Damaged Heart: Mesenchymal Stem Cells, Cell-Based Therapy, and Engineered Heart Tissue

2016 ◽  
Vol 96 (3) ◽  
pp. 1127-1168 ◽  
Author(s):  
Samuel Golpanian ◽  
Ariel Wolf ◽  
Konstantinos E. Hatzistergos ◽  
Joshua M. Hare
Keyword(s):  
Cardiovascular Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Coronary Vessels ◽  
Heart Tissue ◽  
Structure And Function ◽  
Nonischemic Cardiomyopathy ◽  
Cell Based Therapy ◽  
And Function

Mesenchymal stem cells (MSCs) are broadly distributed cells that retain postnatal capacity for self-renewal and multilineage differentiation. MSCs evade immune detection, secrete an array of anti-inflammatory and anti-fibrotic mediators, and very importantly activate resident precursors. These properties form the basis for the strategy of clinical application of cell-based therapeutics for inflammatory and fibrotic conditions. In cardiovascular medicine, administration of autologous or allogeneic MSCs in patients with ischemic and nonischemic cardiomyopathy holds significant promise. Numerous preclinical studies of ischemic and nonischemic cardiomyopathy employing MSC-based therapy have demonstrated that the properties of reducing fibrosis, stimulating angiogenesis, and cardiomyogenesis have led to improvements in the structure and function of remodeled ventricles. Further attempts have been made to augment MSCs' effects through genetic modification and cell preconditioning. Progression of MSC therapy to early clinical trials has supported their role in improving cardiac structure and function, functional capacity, and patient quality of life. Emerging data have supported larger clinical trials that have been either completed or are currently underway. Mechanistically, MSC therapy is thought to benefit the heart by stimulating innate anti-fibrotic and regenerative responses. The mechanisms of action involve paracrine signaling, cell-cell interactions, and fusion with resident cells. Trans-differentiation of MSCs to bona fide cardiomyocytes and coronary vessels is also thought to occur, although at a nonphysiological level. Recently, MSC-based tissue engineering for cardiovascular disease has been examined with quite encouraging results. This review discusses MSCs from their basic biological characteristics to their role as a promising therapeutic strategy for clinical cardiovascular disease.

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 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.

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.

Stem Cell Therapy For The Treatment Of Crohn's Disease; Current Obstacles And Future Hopes. (Mini-Review)

2021 ◽  
Vol 16 ◽  
Author(s):  
Sarah El-Nakeep
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Perianal Fistula ◽  
The United States

Background: Crohn's disease (CD) is an autoimmune disease of the gastrointestinal tract, characterized by relapsing and remitting courses. The disease is debilitating in nature with three prominent phenotypic clinical presentations; fistulizing, stenosing, and inflammatory. Stem cells offer a new hope for CD patients with modifying the immune response and progression of the healing process. Aim: This mini-review discusses the role of stem cells in treating CD, their effectiveness as a new therapy and their current limitations faced. Methods: The author conducted a literature review on recent randomized controlled trials and cohort studies concerned with the topic in question using the following keywords (Crohn's Disease, perianal fistula, Stem cell therapy, mesenchymal stem cells, remission). Results: Clinical trials show that the stem cells are more effective in the CD associated complex perianal fistula than the CD enteritis. Till the time being, there are no standardized guidelines regarding; dose of stem cells used, number of doses administered, route of administration, type of stem cells used. Only one group of researchers proposed a standardized procedure for injecting mesenchymal stem cells in complex perianal fistula, according to their own experience in clinical trials. Moreover, mesenchymal stem cells and their related types (placental, adipose tissue, umbilical tissue, etc.) are the most safe and effective in clinical trials. Currently; the commercially available mesenchymal stem cells preparation (Darvadstrocel (Cx601)) is the only one approved by The United States Food and Drug Administration (FDA) for clinical use in refractory CD associated complex perianal fistula. Conclusions: Stem cell therapy (SCT) shows promise in; inducing remission in refractory Crohn's colitis, and perianal fistula, but further research is required before SCT could be applied to clinical practice guidelines

scholarly journals PROSPECT OF STEM CELL THERAPY TO AVOID CYTOKINE STORM IN SEVERE COVID-19

2020 ◽  
pp. 42-48
Author(s):  
J. A. PAWITAN
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Randomized Clinical Trials ◽  
Case Series ◽  
Multiple Organ ◽  
Cytokine Storm ◽  
Well Design ◽  
Preliminary Study ◽  
Initial Results

Severe COVID-19 cases are mostly due to severe inflammatory reaction and cytokine storm, which may lead to multiple organ failure and death. Until recently, there is no proven effective treatment for severe COVID-19. Mesenchymal stem cells (MSCs) have anti-inflammatory and regenerative properties. Therefore, they are supposed to work on COVID-19, which has failed to recover using other treatments. Therefore, studies are needed to determine the best tissue source of MSCs, the dose, repeat, and route of administration. For this review, we searched various databases, i.e. Pubmed, Science Direct, Springer, and WHO website using keywords: “mesenchymal stem cells” and “COVID-19” at 7 May 2020, without time limits. Various clinical trials on the use of MSCs for COVID-19 were registered, and initial results were reported. Initial results were promising but should be interpreted cautiously, as one was a case report, another one was case series, and one was a preliminary study of seven treated patients compared to three controls, where the baseline conditions were unequal. Therefore, well design randomized clinical trials are needed to get more robust prove.

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