scholarly journals Current status, challenges and perspectives of mesenchymal stem cell-based therapy for cardiac regeneration

2021 ◽  
Vol 10 (3) ◽  
pp. 72-78
Author(s):  
P. M. Docshin ◽  
A. Bairqdar ◽  
A. B. Malashicheva
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Side Population ◽  
Heart Diseases ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Individual Characteristics ◽  
Current Status ◽  
Cell Based Therapy

Modern methods of treating heart failure are similar to the palliative care, since they mostly relieve the symptoms of the disease. The discovery of resident cardiac stem cells gave impetus to the development of “second generation” cell therapy, which quickly moved from animal research to clinical trials with critically ill patients. Many cardiac side population cells have been identified to have stem cells characteristics and some additional individual characteristics, both in vitro and in vivo. The results of clinical studies demonstrated that the stem cell treatment is safe, however, this type of cell-based therapy did not restore cardiac function. Its effects were limited to mildly improving left ventricular systolic pressure and reducing the scar area. Despite that, the promising nature of these therapeutic approaches for heart diseases have contributed to the development of next-generation cell therapy.

scholarly journals Combined Analysis of Endothelial, Hematopoietic, and Mesenchymal Stem Cell Compartments Shows Simultaneous but Independent Effects of Age and Heart Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Carine Ghem ◽  
Lucinara Dadda Dias ◽  
Roberto Tofani Sant’Anna ◽  
Renato A. K. Kalil ◽  
Melissa Markoski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Progenitor Cells ◽  
Heart Diseases ◽  
Left Ventricular ◽  
Syntax Score ◽  
Hematopoietic Stem ◽  
Cell Compartments

Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays. The study included 36 patients referred for coronary artery bypass grafting or valve replacement surgery. A decreased frequency of stem cells was observed in both groups of patients. Left ventricular dysfunction, diabetes, and intermediate risk in EuroSCORE and SYNTAX score were associated with lower EPCs frequency, and the use of aspirin andβ-blockers correlated with a higher frequency of HSCs and EPCs, respectively. Most importantly, the distribution of frequencies in the three stem cell compartments showed independent patterns. The combined investigation of the three stem cell compartments in patients with cardiovascular diseases showed that they are independently affected by the disease, suggesting the investigation of prognostic factors that may be used to determine when autologous stem cells may be used in cell therapy.

scholarly journals Regenerative Cardiovascular Therapies: Stem Cells and Beyond

2019 ◽  
Vol 20 (6) ◽  
pp. 1420 ◽  
Author(s):  
Bernhard Wernly ◽  
Moritz Mirna ◽  
Richard Rezar ◽  
Christine Prodinger ◽  
Christian Jung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Basic Science ◽  
Left Ventricular ◽  
Specific Cell ◽  
Therapeutic Effects ◽  
Cell Processing

Although reperfusion therapy has improved outcomes, acute myocardial infarction (AMI) is still associated with both significant mortality and morbidity. Once irreversible myocardial cell death due to ischemia and reperfusion sets in, scarring leads to reduction in left ventricular function and subsequent heart failure. Regenerative cardiovascular medicine experienced a boost in the early 2000s when regenerative effects of bone marrow stem cells in a murine model of AMI were described. Translation from an animal model to stem cell application in a clinical setting was rapid and the first large trials in humans suffering from AMI were conducted. However, high initial hopes were early shattered by inconsistent results of randomized clinical trials in patients suffering from AMI treated with stem cells. Hence, we provide an overview of both basic science and clinical trials carried out in regenerative cardiovascular therapies. Possible pitfalls in specific cell processing techniques and trial design are discussed as these factors influence both basic science and clinical outcomes. We address possible solutions. Alternative mechanisms and explanations for effects seen in both basic science and some clinical trials are discussed here, with special emphasis on paracrine mechanisms via growth factors, exosomes, and microRNAs. Based on these findings, we propose an outlook in which stem cell therapy, or therapeutic effects associated with stem cell therapy, such as paracrine mechanisms, might play an important role in the future. Optimizing stem cell processing and a better understanding of paracrine signaling as well as its effect on cardioprotection and remodeling after AMI might improve not only AMI research, but also our patients’ outcomes.

scholarly journals Cell-Based Therapy for Stroke

Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Therapeutic Potential ◽  
Host Tissue ◽  
In Vivo Models ◽  
Cell Based Therapy ◽  
Muse Cells

Stem cell-based regenerative therapies may rescue the central nervous system following ischemic stroke. Mesenchymal stem cells exhibit promising regenerative capacity in in vitro studies but display little to no incorporation in host tissue after transplantation in in vivo models of stroke. Despite these limitations, clinical trials using mesenchymal stem cells have produced some functional benefits ascribed to their ability to modulate the host’s inflammatory response coupled with their robust safety profile. Regeneration of ischemic brain tissue using stem cells, however, remains elusive in humans. Multilineage-differentiating stress-enduring (Muse) cells are a distinct subset of mesenchymal stem cells found sporadically in connective tissue of nearly every organ. Since their discovery in 2010, these endogenous reparative stem cells have been investigated for their therapeutic potential against a variety of diseases, including acute myocardial infarction, stroke, chronic kidney disease, and liver disease. Preclinical studies have exemplified Muse cells’ unique ability mobilize, differentiate, and engraft into damaged host tissue. Intravenously transplanted Muse cells in mouse lacunar stroke models afforded functional recovery and long-term engraftment into the host neural network. This mini-review article highlights these biological properties that make Muse cells an exceptional candidate donor source for cell therapy in ischemic stroke. Elucidating the mechanism behind the therapeutic potential of Muse cells will undoubtedly help optimize stem cell therapy for stroke and advance the field of regenerative medicine.

scholarly journals Application of Nanotechnology in Stem-Cell-Based Therapy of Neurodegenerative Diseases

2020 ◽  
Vol 10 (14) ◽  
pp. 4852 ◽  
Author(s):  
Shima Masoudi Asil ◽  
Jyoti Ahlawat ◽  
Gileydis Guillama Barroso ◽  
Mahesh Narayan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Large Scale ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Clinical Scales ◽  
Adverse Health Outcomes ◽  
Cell Based Therapy

In addition to adverse health outcomes, neurological disorders have serious societal and economic impacts on patients, their family and society as a whole. There is no definite treatment for these disorders, and current available drugs only slow down the progression of the disease. In recent years, application of stem cells has been widely advanced due to their potential of self-renewal and differentiation to different cell types which make them suitable candidates for cell therapy. In particular, this approach offers great opportunities for the treatment of neurodegenerative disorders. However, some major issues related to stem-cell therapy, including their tumorigenicity, viability, safety, metastases, uncontrolled differentiation and possible immune response have limited their application in clinical scales. To address these challenges, a combination of stem-cell therapy with nanotechnology can be a solution. Nanotechnology has the potential of improvement of stem-cell therapy by providing ideal substrates for large scale proliferation of stem cells. Application of nanomaterial in stem-cell culture will be also beneficial to modulation of stem-cell differentiation using nanomedicines. Nanodelivery of functional compounds can enhance the efficiency of neuron therapy by stem cells and development of nanobased techniques for real-time, accurate and long-lasting imaging of stem-cell cycle processes. However, these novel techniques need to be investigated to optimize their efficiency in treatment of neurologic diseases.

The Role of Stem Cells in the Therapy of Stroke

2021 ◽  
Vol 19 ◽  
Author(s):  
Maria Ejma ◽  
Natalia Madetko ◽  
Anna Brzecka ◽  
Piotr Alster ◽  
Sławomir Budrewicz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Current Literature ◽  
Reference List ◽  
Medical Subject Headings ◽  
Post Stroke ◽  
Cell Based Therapy ◽  
Future Therapy

Background: Stroke is a major challenge in neurology due to its multifactorial genesis and irreversible consequences. Processes of endogenous post-stroke neurogenesis, although insufficient, may indicate possible direction of future therapy. Multiple research considers stem-cell-based approaches in order to maximize neuroregeneration and minimize post-stroke deficits. Objective: Aim of this study is to review current literature considering post-stroke stem-cell- based therapy and possibilities of inducing neuroregeneration after brain vascular damage. Methods: Papers included in this article were obtained from PubMed and MEDLINE databases. The following medical subject headings (MeSH) were used: “stem cell therapy”, “post-stroke neurogenesis”, “stem-cells stroke”, “stroke neurogenesis”, “stroke stem cells”, “stroke”, “cell therapy”, “neuroregeneration”, “neurogenesis”, “stem-cell human”, “cell therapy in human”. Ultimate inclusion was made after manual review of the obtained reference list. Results: Attempts of stimulating neuroregeneration after stroke found in current literature include supporting endogenous neurogenesis, different routes of exogenous stem cells supplying and extracellular vesicles used as a method of particle transport. Conclusion: Although further research in this field is required, post stroke brain recovery supported by exogenous stem cells seems to be promising future therapy revolutionizing modern neurology.

Prospects for Stem Cell-Based Regenerative Therapies in India

StemJournal ◽  
2021 ◽  
pp. 1-11
Author(s):  
Dinesh Boopalan ◽  
Ramanan Pandian ◽  
Gokul Kesavan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Large Scale ◽  
Phase 1 ◽  
Current Status ◽  
Beta Thalassemia ◽  
Novel Coronavirus ◽  
Regenerative Therapies

Stem cells offer a promising therapeutic strategy to not only treat several incurable diseases but also regenerate damaged tissues. The current global boom in the field of stem cell and regenerative therapies had led to India becoming a global hotspot for stem cell-based therapies. In this review, we assess the current status of stem cell therapy trials in India and show that the bone marrow-derived stem cells, like mesenchymal stem/stromal cells (MSCs), are predominantly used. Phase 1 and 2 clinical trials have also used MSCs to alleviate symptoms of severe novel coronavirus infections. Recent breakthroughs in gene editing technologies, combined with stem cell therapy, can be effectively harnessed to devise large-scale and affordable treatments for haematological diseases that are highly prevalent in India, like beta-thalassemia and sickle cell diseases. Innovations in stem cell therapy in India can make treatments more affordable to address the needs of in-country patients.

Abstract 195: Leukemia Inhibitory Factor Stimulates Cardiac Stem Cell--Derived Cardiomyocyte Renewal After Myocardial Infarction Using a Genetic Fate-Mapping Study

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Masato Kanda ◽  
Toshio Nagai ◽  
Toshinao Takahashi ◽  
Mei Lan Liu ◽  
Naomichi Kondou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Stem Cell ◽  
Leukemia Inhibitory Factor ◽  
Side Population ◽  
Treated Group ◽  
Left Ventricular ◽  
Inhibitory Factor ◽  
Cardiac Stem Cells ◽  
Fate Mapping

Cardiac stem cells or precursor cells have the potential to regenerate cardiomyocytes, but their role in the efficacy of cardioprotective drugs remains controversial. Therefore, using a genetic fate-mapping model, we tested the hypothesis that leukemia inhibitory factor (LIF) influences cardiac stem cells and stimulates endogenous cardiomyocyte renewal after myocardial infarction (MI). We generated MerCreMer-LacZ mice in which more than 99.9% of the cardiomyocytes in the left ventricular field showed positive 5-bromo-4-chloro-3-indolyl-β-d-galactoside (Xgal) staining just after tamoxifen injection (5mg/kg/d for 2 weeks). Thus, every Xgal-negative cardiomyocyte was derived from a stem or precursor cell after tamoxifen administration. The number of Xgal-negative cardiomyocytes did not change during normal aging spanning 1 year. However, at 3 months after MI, the MI mice had more Xgal-negative cells than the control mice (57.0 ± 12.0 and 3.0 ± 2.6 cells per section, respectively; P < 0.01). The side population (SP) cell fraction contained label-retaining cells, which differentiated into Xgal-negative cardiomyocytes after MI. Among the cytokines secreted after MI, LIF expression increased to 130 fold in MI mice but rapidly decreased within 1 week. Therefore, we injected the LIF plasmid at the time of MI to keep blood LIF concentrations high and examined its effect on regeneration. At 1 month after MI, the MI + LIF group (118.6 ± 51.5 cells per section) had more Xgal-negative cells than the MI + PBS group (37.0 ± 5.5 cells per section; P < 0.05). Echocardiography showed significant recovery of fractional shortening in the LIF-treated group only. Next, we immunohistochemically analyzed the effect of LIF on SP cells. On BrdU administration at 1 week after MI, the percentages of BrdU-positive SP cells in LIF- and PBS-treated mice were 59%, and 35%, respectively, suggesting that LIF influenced SP cell proliferation. The percentages of Ki67- and phosphorylated histone-3-positive SP cells were also higher in LIF-treated mice. Taken together, LIF may stimulate stem cell-derived cardiomyocyte regeneration in part by activating SP cells. We believe our findings will help provide a novel therapeutic strategy for cardiogenesis.

scholarly journals Prospects of Therapeutic Target and Directions for Ischemic Stroke

2021 ◽  
Vol 14 (4) ◽  
pp. 321
Author(s):  
Jung Hak Kim ◽  
So Young Kim ◽  
Bokyung Kim ◽  
Sang Rae Lee ◽  
Sang Hoon Cha ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Neurological Deficits ◽  
Cell Based Therapy

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.

scholarly journals Cell biobank as a necessary infrastructure for the development and implementation of mesenchymal stem cell-based therapy in the treatment of anthracycline-induced cardiotoxicity. Literature review and own data

2020 ◽  
Vol 19 (6) ◽  
pp. 2733
Author(s):  
L. Yu. Grivtsova ◽  
O. E. Popovkina ◽  
N. N. Dukhova ◽  
O. A. Politiko ◽  
V. V. Yuzhakov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Cancer Patients ◽  
Experimental Studies ◽  
Hematopoietic Stem ◽  
Trophic Effect ◽  
Cell Based Therapy ◽  
Limited Effectiveness ◽  
A Cell

Cardiovascular diseases, along with cancer, are the leading causes of death worldwide. Although modern pharmacological treatment of various cardiomyopathies can slow the development of myocardial dysfunction, they have limited effectiveness in patients with end-stage disease. Many researchers believe that heart transplantation is the only radical treatment in this case. However, the lack of donors and the high operation cost require careful selection of surgical candidates. With the introduction of molecular and cell biology into medical practice, today, stem cell therapy can become an alternative method of nonsurgical restoration of myocardial functions. The most studied and attractive is the use of mesenchymal stem cells (MSCs). MSCs differ from hematopoietic stem cells used as support for hematopoiesis in high-dose chemotherapy by the following features: pronounced trophic effect, immune tolerance, the ability to suppress alloreactivity and autoimmune disorders. An important stage in the implementation of cell therapy is the creation of a cell biobank of MSCs. In A.F.Tsyb Medical Radiological Research Center, this work has been carried out since1984. Asignificant number of experimental studies have been carried out, confirming the possibility of clinical implementation of this approach. A method for obtaining stable cultures of MSCs and cardiomyoblasts from bone marrow cells was developed and approvals were obtained. Experimental studies of cell therapy are also being conducted to overcome anthracycline-induced cardiotoxicity in cancer patients.This article is devoted to practical application of MSC-based therapy, in particular, in cancer patients with cardiotoxicity, as well as to the issues of creating a cell biobank for treatment with MSCs.

scholarly journals Stem cell-based therapy for COVID-19 and ARDS: a systematic review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gabriele Zanirati ◽  
Laura Provenzi ◽  
Lucas Lobraico Libermann ◽  
Sabrina Comin Bizotto ◽  
Isadora Machado Ghilardi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Clinical Studies ◽  
Case Series ◽  
Potential Candidate ◽  
Phase I Clinical Trials ◽  
Cell Based Therapy

AbstractDespite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use.

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