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 ◽  
...  

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.

2021 ◽  
Vol 19 ◽  
Author(s):  
Aditya A Singh ◽  
Akash Kharwar ◽  
Manoj P. Dandekar

Background: Stroke is a serious neurovascular problem and the leading cause of disability and death worldwide. The disrupted demand to supply ratio of blood and glucose during cerebral ischemia develops hypoxic shock, and subsequently necrotic neuronal death in the affected regions. Multiple causal factors like age, sex, race, genetics, diet, and lifestyle play an important role in the occurrence as well as progression of post-stroke deleterious events. These biological and environmental factors may be contributed to vasculature variable architecture and abnormal neuronal activity. Since recombinant tissue plasminogen activator is the only clinically effective clot bursting drug, there is a huge unmet medical need for newer therapies for the treatment of stroke. Innumerous therapeutic interventions have shown promise in the experimental models of stroke but failed to translate it into clinical counterparts. Methods: Original publications regarding pathophysiology, preclinical experimental models, new targets and therapies targeting ischemic stroke have been reviewed since the 1970s. Results: We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Results : We highlighted the critical underlying pathophysiological mechanisms of cerebral stroke and preclinical stroke models. We discuss the strengths and caveats of widely used ischemic stroke models, and commented on the potential translational problems. We also describe the new emerging treatment strategies, including stem cell therapy, neurotrophic factors and gut microbiome-based therapy for the management of post-stroke consequences. Conclusion: There are still many inter-linked pathophysiological alterations with regards to stroke, animal models need not necessarily mimic the same conditions of stroke pathology and newer targets and therapies are the need of the hour in stroke research.


Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jinho Lee ◽  
Kyu-Yong Lee ◽  
Young-Seo Kim ◽  
Hyun Young Kim ◽  
Hyuk Sung Kwon ◽  
...  

Introduction: Stem cell therapy (SCT) has been proposed for the treatment of neurological disorders. Although there isinsufficient clinical evidence to support its efficacy, unproven SCTs are being performed worldwide. Hypothesis: In this study, we investigated the perspectives and expectations of chronic ischemic stroke patients and physicians about SCTs. Methods: A total of 250 chronic ischemic stroke patients were interviewed at 4 hospitals. Structured open and closed questions about SCT for chronic stroke were asked by trained interviewers using the conventional in-person method. In addition, 250 stroke-related physicians were randomly interviewed via an e-mail questionnaire. Results: Of the 250 patients (mean 63 years, 70% male), 121 (46%) responded that they wanted to receive SCT in spite of its unknown side effects. Around 60% of the patients anticipated physical, emotional, and psychological improvement after SCT, and 158 (63%) believed that SCT might prevent strokes. However, physicians had much lower expectations about the effectiveness of SCTs, which was not in line with patient expectations. Multivariate analysis revealed that male gender (OR: 2.00, 95% CI: 1.10-3.64), longer disease duration (OR: 1.01, 95% CI:1.00-1.02), higher modified Rankin Scale score (OR: 1.30, 95% CI 1.06-1.60), and familiarity with stem cells (OR: 1.86, 95% CI: 1.10-3.15) were independently associated with wanting SCT. The major source of information about SCT was television (68%), and the most reliable source was physicians (49%). Conclusion: Patients have unfounded expectations that SCT will improve their functioning. Considering our finding that the major source of information on stem cells is media channels but not the physician, to decrease patients’ inappropriate exposure, doctors should make more effort to educate patients using mass media with accurate information.


2021 ◽  
Author(s):  
Sevil Kestane

This overview was evaluated by the development of diabetic retinopathy (DR) and the stem cell therapy approach. DR is a microvascular complication of diabetes mellitus, characterized by damage to the retinal blood vessels leading to progressive loss of vision. However, the pathophysiological mechanisms are complicated and not completely understood yet. The current treatment strategies have included medical, laser, intravitreal, and surgical approaches. It is known that the use of mesenchymal stem cells (MSC), which has a great potential, is promising for the treatment of many degenerative disorders, including the eye. In retinal degenerative diseases, MSCs were ameliorated retinal neurons and retinal pigmented epithelial cells in both in vitro and in vivo studies. Stem cell therapies show promise in neurodegenerative diseases. However, it is very important to know which type of stem cell will be used in which situations, the amount of stem cells to be applied, the method of application, and its physiological/neurophysiological effects. Therefore, it is of great importance to evaluate this subject physiologically. After stem cell application, its safety and efficacy should be followed for a long time. In the near future, widespread application of regenerative stem cell therapy may be a standard treatment in DR.


Stroke ◽  
2020 ◽  
Vol 51 (9) ◽  
pp. 2854-2862 ◽  
Author(s):  
You Jeong Park ◽  
Kuniyasu Niizuma ◽  
Maxim Mokin ◽  
Mari Dezawa ◽  
Cesar V. Borlongan

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.


2020 ◽  
Vol 10 (14) ◽  
pp. 4852 ◽  
Author(s):  
Shima Masoudi Asil ◽  
Jyoti Ahlawat ◽  
Gileydis Guillama Barroso ◽  
Mahesh Narayan

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.


2021 ◽  
Author(s):  
Wonjae Lee ◽  
Zhonlin Lyu ◽  
Jon Park ◽  
Kwang-Min Kim ◽  
Hye-jin Jin ◽  
...  

Abstract Stem cell therapy is emerging as a promising treatment option to restore a neurological function after ischemic stroke. Despite the growing number of candidate stem cell types, each with unique characteristics, there is a lack of experimental platform to systematically evaluate their neurorestorative potential. When stem cells are transplanted into ischemic brain, the therapeutic efficacy primarily depends on the response of the neurovascular unit (NVU) to these extraneous cells. In this work, we developed an ischemic stroke microphysiological system (MPS) with a functional NVU on a microfluidic chip. Our new chip design facilitated the incorporated cells to form a functional blood-brain barrier (BBB) and restore their in vivo-like behaviors in both healthy and ischemic conditions. We utilized this MPS to track the transplanted stem cells and characterize their neurorestorative behaviors reflected in gene expression levels. Each type of stem cells showed unique neurorestorative effects, primarily through supporting the endogenous recovery, rather than through direct cell replacement. And the recovery of synaptic activities, critical for neurological function, was more tightly correlated with the recovery of the structural and functional integrity in NVU, rather than with the regeneration of neurons itself.


2020 ◽  
Vol 15 (2) ◽  
pp. 173-186 ◽  
Author(s):  
Shahin Ahmadian ◽  
Mahdi Mahdipour ◽  
Mohammad Pazhang ◽  
Sepideh Sheshpari ◽  
Halimeh Mobarak ◽  
...  

Background: Infertility is a major problem worldwide. Various strategies are being used to develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current developments. Objective: Different published studies on stem cell-based therapy for the treatment of various types of ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female population in animal or human clinical studies are systematically reviewed. Method: We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest. A comprehensive online search was done using the criteria targeting the application of stem cells in animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of studies. The stem cell type, source, dosage, route of administration were highlighted in various POI animals models. Non-relevant and review articles were excluded. Outcomes: 648 published studies were identified during the initial comprehensive search process from which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase fertility rate. Conclusion: The evidence suggests that stem cell-based therapies could be considered as an alternative modality to deal with women undergoing POI.


2021 ◽  
Vol 11 (5) ◽  
pp. 653
Author(s):  
Sareh Pandamooz ◽  
Benjamin Jurek ◽  
Mohammad Saied Salehi ◽  
Mandana Mostaghel ◽  
Jaleel A. Miyan ◽  
...  

In the recent review published in Brain Sciences, Othman and Tan suggested several preconditioning strategies to improve stem cell therapy after ischemic brain injury [...]


Author(s):  
Prithiv Kumar K R

Severe illness such as bipolar is most common in developing countries and most populations are affected. Stem cell therapy has been a solution to this cognitive or social defect. This chapter is all about balancing and targeting modulation in the brain but also regenerating cells. With pathological damage in mental illness, there is novel interference such as modulation of a particular cell population. In the particular case of damage, oligodendrites played a crucial role. In this chapter, oligodendrites reveal calcium signals in neural cells. The stimulating mechanism of oligodendrites helps in the proliferation, maturation and myelination response of transplanted cells. The calcium signaling response regulates the neural progenitor cell proliferation, migration, differentiation synaptic plasticity which involves neuropsychiatric diseases in humans. Protein annotation and protein-protein interaction have been highlighted in this chapter. There are 119 calcium-activated proteins in the neuropsychiatry of the human brain. The calcium channel stimulating of stem cells zeros on the advantage of calcium stimulated stem cells and transplants the signal, to channel the drugs in a devised delivery system. This local delivery guidance of the brain delivery method is visualized using brain imaging techniques, providing a unique approach to treatment in psychiatry patients. It was found in our experiments that preconditioning stem cell therapy had high potential during transplantation and advised cared stimulations in procaine shell, synaptic modulation and myelin repair.


Author(s):  
Guoyang Zhou ◽  
Yongjie Wang ◽  
Shiqi Gao ◽  
Xiongjie Fu ◽  
Yang Cao ◽  
...  

Ischemic stroke (IS) remains one of the major causes of death and disability due to the limited ability of central nervous system cells to regenerate and differentiate. Although several advances have been made in stroke therapies in the last decades, there are only a few approaches available to improve IS outcome. In the acute phase of IS, mechanical thrombectomy and the administration of tissue plasminogen activator have been widely used, while aspirin or clopidogrel represents the main therapy used in the subacute or chronic phase. However, in most cases, stroke patients fail to achieve satisfactory functional recovery under the treatments mentioned above. Recently, cell therapy, especially stem cell therapy, has been considered as a novel and potential therapeutic strategy to improve stroke outcome through mechanisms, including cell differentiation, cell replacement, immunomodulation, neural circuit reconstruction, and protective factor release. Different stem cell types, such as mesenchymal stem cells, marrow mononuclear cells, and neural stem cells, have also been considered for stroke therapy. In recent years, many clinical and preclinical studies on cell therapy have been carried out, and numerous results have shown that cell therapy has bright prospects in the treatment of stroke. However, some cell therapy issues are not yet fully understood, such as its optimal parameters including cell type choice, cell doses, and injection routes; therefore, a closer relationship between basic and clinical research is needed. In this review, the role of cell therapy in stroke treatment and its mechanisms was summarized, as well as the function of different stem cell types in stroke treatment and the clinical trials using stem cell therapy to cure stroke, to reveal future insights on stroke-related cell therapy, and to guide further studies.


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