scholarly journals Functionally Improved Mesenchymal Stem Cells to Better Treat Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Zhi Chen ◽  
Long Chen ◽  
Chunyu Zeng ◽  
Wei Eric Wang
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Clinical Trials ◽  
Causes Of Death ◽  
The Other ◽  
Preclinical Studies ◽  
Significant Progress ◽  
Poor Survival ◽  
And Function ◽  
Host Myocardium

Myocardial infarction (MI) is one of the leading causes of death worldwide. Mesenchymal stem cell (MSC) transplantation is considered a promising approach and has made significant progress in preclinical studies and clinical trials for treating MI. However, hurdles including poor survival, retention, homing, and differentiation capacity largely limit the therapeutic effect of transplanted MSCs. Many strategies such as preconditioning, genetic modification, cotransplantation with bioactive factors, and tissue engineering were developed to improve the survival and function of MSCs. On the other hand, optimizing the hostile transplantation microenvironment of the host myocardium is also of importance. Here, we review the modifications of MSCs as well as the host myocardium to improve the efficacy of MSC-based therapy against MI.

scholarly journals HEMOPOIEITC SPLEEN COLONY STUDIES

1967 ◽  
Vol 125 (4) ◽  
pp. 703-720 ◽  
Author(s):  
J. L. Curry ◽  
J, J. Trentin ◽  
N. Wolf
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Morphological Differentiation ◽  
Erythroid Differentiation ◽  
Colony Growth ◽  
The Other ◽  
Colony Development ◽  
Undifferentiated Cells ◽  
Specific Stimulation ◽  
And Function

The polycythemic repression of erythropoiesis and the restoration of erythropoiesis by specific stimulation were studied in the spleen colony system in irradiated mice. 1. A 5 day period of erythropoietin stimulation (exogenous erythropoietin) or repression (polycythemia) of the bone marrow donor only, does not significantly alter the number or type of colonies formed by the transplanted marrow cells. 2. Erythropoietin stimulation did not alter the number or type of endogenous colonies formed in mice receiving 580 R. Erythropoietin repression (polycythemia) markedly reduced the growth but not the number of erythroid colonies, while not affecting the other types of colonies formed endogenously. 3. Erythropoietin stimulation of the irradiated recipient during colony growth did not alter the number or type of spleen colonies formed by transplanted marrow. Erythropoietin repression by polycythemia during colony growth completely suppressed the appearance of morphologically erythroid colonies without significantly altering the incidence of the other colony types. This effect of polycythemia was completely prevented by exogenous erythropoietin. Irradiated mice are therefore presumed to be secreting sufficient erythropoietin for maximal erythroid colony development. 4. The erythroid colonies suppressed by polycythemia were recognizable as microscopic foci of undifferentiated cells. Exposure of these foci to erythropoietin stimulation at different periods in their development was manifested by different degrees of growth and differentiation, from which it is apparent that erythropoietin stimulates not only morphological differentiation but also rapid mitosis. Retransplantation of either erythroid or of neutrophilic primary spleen colonies gave rise to both erythroid and neutrophilic secondary spleen colonies. The percentage of erythroid secondary colonies was slightly but significantly higher among the progeny of transplanted erythroid primary colonies than among the progeny of transplanted neutrophilic primary colonies. On the basis of these and other results, a working hypothesis is proposed for factors controlling the growth and differentiation of spleen colonies from transplanted bone marrow. It is postulated that most but perhaps not all spleen colony-forming units are pluripotent hemopoietic stem cells. It is further postulated that hemopoietic-inductive microenvironments (HIM) of different kinds exist in both the spleen and the bone marrow, and that these determine the differentiation of pluripotent stem cells into each of the lines of hemopoietic differentiation. Erythropoietin therefore may "induce" erythroid differentiation of only those stem cells under the influence of an erythroid HIM. Alternatively erythropoietin may act only as a growth and function stimulant of those stem cells that have been "induced" by an erythroid HIM into a state of erythropoietin responsiveness. In the latter case morphological differentiation presumably results from the functional activity stimulated by ESF.

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 Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yunyu Zhao ◽  
Zhipeng Yan ◽  
Ying Liu ◽  
Yue Zhang ◽  
Jie Shi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Preclinical Studies ◽  
Patient Prognosis

AbstractPulmonary fibrosis (PF) is a chronic, progressive, fibrotic interstitial disease of the lung with poor prognosis and without effective treatment currently. Data from previous coronavirus infections, such as the Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome, as well as current clinical evidence from the Coronavirus disease 2019 (COVID-19), support that SARS-CoV-2 infection may lead to PF, seriously impacting patient prognosis and quality of life. Therefore, effective prevention and treatment of PF will improve patient prognosis and reduce the overall social and economic burdens. Stem cells, especially mesenchymal stem cells (MSCs) have many great advantages, including migration to damaged lung tissue and secretion of various paracrine factors, thereby regulating the permeability of endothelial and epithelial cells, reducing inflammatory response, promoting tissue repair and inhibiting bacterial growth. Clinical trials of MSCs for the treatment of acute lung injury, PF and severe and critically ill COVID-19 are ongoing. The purpose of this study is to systematically review preclinical studies, explored the effectiveness of MSCs in the treatment of bleomycin (BLM)-induced pulmonary fibrosis and analyze the potential mechanism, combined with clinical trials of current MSCs for idiopathic pulmonary fibrosis (IPF) and COVID-19, so as to provide support for clinical research and transformation of MSCs. Searching PubMed and Embase (− 2021.4) identified a total of 36 preclinical studies of MSCs as treatment of BLM-induced acute lung injury and PF in rodent models. Most of the studies showed the MSCs treatment to reduce BLM-induced lung tissue inflammatory response, inflammatory cell infiltration, inflammatory cytokine expression, extracellular matrix production and collagen deposition, and to improve Ashcroft score. The results of present studies indicate that MSCs may serve as a potential therapeutic modality for the treatment of PF, including viral-induced PF and IPF.

scholarly journals Therapeutic Potential of Human Stem Cell Implantation in Alzheimer’s Disease

2021 ◽  
Vol 22 (18) ◽  
pp. 10151
Author(s):  
Hau Jun Chan ◽  
Yanshree ◽  
Jaydeep Roy ◽  
George Lim Tipoe ◽  
Man-Lung Fung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Morris Water Maze Test ◽  
Preclinical Studies

Alzheimer’s disease (AD) is a progressive debilitating neurodegenerative disease and the most common form of dementia in the older population. At present, there is no definitive effective treatment for AD. Therefore, researchers are now looking at stem cell therapy as a possible treatment for AD, but whether stem cells are safe and effective in humans is still not clear. In this narrative review, we discuss both preclinical studies and clinical trials on the therapeutic potential of human stem cells in AD. Preclinical studies have successfully differentiated stem cells into neurons in vitro, indicating the potential viability of stem cell therapy in neurodegenerative diseases. Preclinical studies have also shown that stem cell therapy is safe and effective in improving cognitive performance in animal models, as demonstrated in the Morris water maze test and novel object recognition test. Although few clinical trials have been completed and many trials are still in phase I and II, the initial results confirm the outcomes of the preclinical studies. However, limitations like rejection, tumorigenicity, and ethical issues are still barriers to the advancement of stem cell therapy. In conclusion, the use of stem cells in the treatment of AD shows promise in terms of effectiveness and safety.

scholarly journals Co-Transplantation of Hypoxia Pretreated Human Adipose Derived Mesenchymal Stem Cells and Cord Blood Mononuclear Cells to Treat Rats With Acute Myocardial Infarction

2020 ◽  
Author(s):  
Hang Xiang ◽  
Tianyuan Xiang ◽  
Hongxia Zhang ◽  
Ann Xu ◽  
Matthew John Horwedel ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mononuclear Cells ◽  
The Other ◽  
In Vivo Studies ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

Abstract BackgroundHuman adipose derived mesenchymal stem cells (ASCs) are ideal candidates for the treatment of acute myocardial infarction (AMI), due to their favorable availability and regenerative potential. However, in vivo studies showed that ASCs are not resilient at the infarcted area, for a shortage of blood and oxygen supply. Material and methodsTo solve the problem of living in the hypoxic environment, we accommodated ASCs within the hypoxic condition. To enhance the capillary system, we combined the hypoxic pretreated ASCs (HP-ASCs) with cord blood mononuclear cells (CBMNCs), which have a great potential for neovascularization. We hypothesized that this combination system would improve the transplantation efficiency. ResultsIn vitro study showed that HP-ASCs had a wide range of paracrine function, with the incretion growth factors and their receptors, which would support the cell survivals. In addition, HP-ASCs also gained potentials in hypoxic adaptation (increased expression of HO-1 and SDF-1), as well as homing and immigrating abilities (CXCR4, ICAM-1 and ICAM-2). In vivo studies showed that, 30 days after transplantation in AMI rats, the HP-ASCs group had a better improvement in cardiac function; reduction of the infarct size; and decrease of ASCs death than the other groups (HP-ASCs > HP-ASCs + CBMNCs ≧ CBMNCs > PBS) (p<0.05). However, the combined group of HP-ASCs and CBMNCs had more significant angiogenesis than the other groups (HP-ASCs + CBMNCs > CBMNCs > HP-ASCs > PBS) (p <0.05).ConclusionsHP-ASCs alone had a greater potential in improving cardiac function in AMI rats. However, the combination of HP-ASCs and CBMNCs had a better result in angiogenesis.

scholarly journals Low High-Density Lipoprotein and Risk of Myocardial Infarction

2015 ◽  
Vol 9 ◽  
pp. CMC.S26624 ◽  
Author(s):  
A. Ramirez ◽  
P. P. Hu
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trials ◽  
Independent Risk Factor ◽  
Density Lipoprotein ◽  
Structure And Function ◽  
New Agents ◽  
Low Hdl ◽  
And Function ◽  
Relationship Of ◽  
The Relationship

Low HDL is an independent risk factor for myocardial infarction. This paper reviews our current understanding of HDL, HDL structure and function, HDL subclasses, the relationship of low HDL with myocardial infarction, HDL targeted therapy, and clinical trials and studies. Furthermore potential new agents, such as alirocumab (praluent) and evolocumab (repatha) are discussed.

scholarly journals Mesenchymal stem cells for inflammatory airway disorders: promises and challenges

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Xing-Liang Fan ◽  
Zhao Zhang ◽  
Chui Yan Ma ◽  
Qing-Ling Fu
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Mesenchymal Stem Cells ◽  
Clinical Setting ◽  
Lung Diseases ◽  
Preclinical Studies ◽  
Immunomodulatory Effects ◽  
Paracrine Effects ◽  
Clinical Therapy

Abstract The regenerative and immunomodulatory characteristics of mesenchymal stem cells (MSCs) make them attractive in the treatment of many diseases. Although they have shown promising preclinical studies of immunomodulation and paracrine effects in inflammatory airway disorders and other lung diseases, there are still challenges that have to be overcome before MSCs can be safely, effectively, and routinely applied in the clinical setting. A good understanding of the roles and mechanisms of the MSC immunomodulatory effects will benefit the application of MSC-based clinical therapy. In this review, we summarize the promises and challenges of the preclinical and clinical trials of MSC therapies, aiming to better understand the role that MSCs play in attempt to treat inflammatory airway disorders.

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