Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Kawabori, Masahito; Shichinohe, Hideo; Kuroda, Satoshi; Houkin, Kiyohiro

doi:10.3390/ijms21197380

Cited by 128 publications

(101 citation statements)

References 116 publications

(238 reference statements)

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“…MSC treatment promotes NSC migration after the release of neurotrophic factors beneficial to angiogenesis. After proliferation and migration, NSCs differentiate into different mature neurons according to the local microenvironment in which they are located to repair damaged brain areas ( Kawabori et al, 2020a ). Angiogenesis plays a crucial role in the differentiation of NSCs into mature neurons in the ischemic area, as observed in in vitro experiments ( Shen et al, 2004 ) and also in a recent animal study reporting that angiogenesis in the cortex can induce NSC transition from a proliferative form to a differentiated one ( Shen et al, 2004 ).…”

Section: Protective Mechanisms Regulating Stem Cell Therapy After Ismentioning

confidence: 99%

Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies

Zhou

Wang

Gao

et al. 2021

Front. Cell Dev. Biol.

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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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Section: Protective Mechanisms Regulating Stem Cell Therapy After Ismentioning

confidence: 99%

Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies

Zhou

Wang

Gao

et al. 2021

Front. Cell Dev. Biol.

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“…Besides, there is no effective treatment in subacute, chronic, and late chronic stage of stroke except neurorehabilitation [ 16 ] and prevention of recurrent stroke [ 17 ]. Cell, especially stem/progenitor cell transplantation holds great promise as an effective strategy for stroke treatment according to the results of numerous animal studies and clinical trials [ 18 , 19 , 20 ]. Various types of stem cells including embryonic stem cells, induced pluripotent and reprogrammed stem cells, bone marrow mononuclear cells, hematopoietic stem cells, mesenchymal stem cells, neural stem/precursor cells, olfactory ensheathing cells, vascular progenitors, and others have been studied and demonstrated therapeutic benefits (for review see [ 18 , 21 ]).…”

Section: Ischemic Strokementioning

confidence: 99%

“…Cell, especially stem/progenitor cell transplantation holds great promise as an effective strategy for stroke treatment according to the results of numerous animal studies and clinical trials [ 18 , 19 , 20 ]. Various types of stem cells including embryonic stem cells, induced pluripotent and reprogrammed stem cells, bone marrow mononuclear cells, hematopoietic stem cells, mesenchymal stem cells, neural stem/precursor cells, olfactory ensheathing cells, vascular progenitors, and others have been studied and demonstrated therapeutic benefits (for review see [ 18 , 21 ]). However, these studies did not reveal the most effective single stem cell type, as well as optimal cell dose, administration routes, and transplantation time window.…”

Section: Ischemic Strokementioning

confidence: 99%

Combined Cell Therapy in the Treatment of Neurological Disorders

et al. 2020

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Cell therapy of neurological diseases is gaining momentum. Various types of stem/progenitor cells and their derivatives have shown positive therapeutic results in animal models of neurological disorders and in clinical trials. Each tested cell type proved to have its advantages and flaws and unique cellular and molecular mechanism of action, prompting the idea to test combined transplantation of two or more types of cells (combined cell therapy). This review summarizes the results of combined cell therapy of neurological pathologies reported up to this point. The number of papers describing experimental studies or clinical trials addressing this subject is still limited. However, its successful application to the treatment of neurological pathologies including stroke, spinal cord injury, neurodegenerative diseases, Duchenne muscular dystrophy, and retinal degeneration has been reported in both experimental and clinical studies. The advantages of combined cell therapy can be realized by simple summation of beneficial effects of different cells. Alternatively, one kind of cells can support the survival and functioning of the other by enhancing the formation of optimum environment or immunomodulation. No significant adverse events were reported. Combined cell therapy is a promising approach for the treatment of neurological disorders, but further research needs to be conducted.

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“…However, successful transplantation of exogenous stem cells is still hindered by several technical and logistical problems. The specific cell type used is the principal concern due to ethical issues, and researchers must also consider the source as well as the location, dosage, route, and timing of administration (Fernández-Susavila et al, 2019;Kawabori et al, 2020). A series of conditions following a stroke, including neuroinflammation, and immune response activation not only seriously affect the survival of grafted NSCs but also facilitate their differentiation into glial cells; the potential tumorigenicity of transplanted cells is also a concern (Ideguchi et al, 2008;Datta et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Traditional Chinese Medicine Monomers: Novel Strategy for Endogenous Neural Stem Cells Activation After Stroke

Chen

et al. 2021

Front. Cell. Neurosci.

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Stem cell therapy, which has become a potential regenerative medical treatment and a promising approach for treating brain injuries induced by different types of cerebrovascular disease, has various application methods. Activation of endogenous neural stem cells (NSCs) can enable infarcted neuron replacement and promote neural networks’ regeneration without the technical and ethical issues associated with the transplantation of exogenous stem cells. Thus, NSC activation can be a feasible strategy to treat central nervous system (CNS) injury. The potential molecular mechanisms of drug therapy for the activation of endogenous NSCs have gradually been revealed by researchers. Traditional Chinese medicine monomers (TCMs) are active components extracted from Chinese herbs, and some of them have demonstrated the potential to activate proliferation and neurogenesis of NSCs in CNS diseases. Ginsenoside Rg1, astragaloside IV (AST), icariin (ICA), salvianolic acid B (Sal B), resveratrol (RES), curcumin, artesunate (ART), and ginkgolide B (GB) have positive effects on NSCs via different signaling pathways and molecules, such as the Wingless/integrated/β-catenin (Wnt/β-catenin) signaling pathway, the sonic hedgehog (Shh) signaling pathway, brain-derived neurotrophic factor (BDNF), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1). This article may provide further motivation for researchers to take advantage of TCMs in studies on CNS injury and stem cell therapy.

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Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke

Cited by 128 publications

References 116 publications

Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies

Potential Mechanisms and Perspectives in Ischemic Stroke Treatment Using Stem Cell Therapies

Combined Cell Therapy in the Treatment of Neurological Disorders

Traditional Chinese Medicine Monomers: Novel Strategy for Endogenous Neural Stem Cells Activation After Stroke

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