scholarly journals Revisiting Stem Cell-Based Clinical Trials for Ischemic Stroke

2020 ◽  
Vol 12 ◽  
Author(s):  
Joy Q. He ◽  
Eric S. Sussman ◽  
Gary K. Steinberg
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Types ◽  
Complex Problem ◽  
Review Article ◽  
Ischemic Brain ◽  
Cell Lineages ◽  
Ischemic Brain Tissue

Stroke is the leading cause of serious long-term disability, significantly reducing mobility in almost half of the affected patients aged 65 years and older. There are currently no proven neurorestorative treatments for chronic stroke. To address the complex problem of restoring function in ischemic brain tissue, stem cell transplantation-based therapies have emerged as potential restorative therapies. Aligning with the major cell types found within the ischemic brain, stem-cell-based clinical trials for ischemic stroke have fallen under three broad cell lineages: hematopoietic, mesenchymal, and neural. In this review article, we will discuss the scientific rationale for transplanting cells from each of these lineages and provide an overview of published and ongoing trials using this framework.

Cell therapy for ischemic stroke. Stem cell types and results of pre-clinical trials

2018 ◽  
Vol 118 (9) ◽  
pp. 69 ◽  
Author(s):  
D. D. Namestnikova ◽  
R. T. Tairova ◽  
K. K. Sukhinich ◽  
E. A. Cherkashova ◽  
I. L. Gubskiy ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Cell Types

scholarly journals A Look into Stem Cell Therapy: Exploring the Options for Treatment of Ischemic Stroke

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cesar Reis ◽  
Michael Wilkinson ◽  
Haley Reis ◽  
Onat Akyol ◽  
Vadim Gospodarev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Survival Rates ◽  
Cell Types ◽  
Therapeutic Benefit ◽  
Cell Therapies

Neural stem cells (NSCs) offer a potential therapeutic benefit in the recovery from ischemic stroke. Understanding the role of endogenous neural stem and progenitor cells under normal physiological conditions aids in analyzing their effects after ischemic injury, including their impact on functional recovery and neurogenesis at the site of injury. Recent animal studies have utilized unique subsets of exogenous and endogenous stem cells as well as preconditioning with pharmacologic agents to better understand the best situation for stem cell proliferation, migration, and differentiation. These stem cell therapies provide a promising effect on stimulation of endogenous neurogenesis, neuroprotection, anti-inflammatory effects, and improved cell survival rates. Clinical trials performed using various stem cell types show promising results to their safety and effectiveness on reducing the effects of ischemic stroke in humans. Another important aspect of stem cell therapy discussed in this review is tracking endogenous and exogenous NSCs with magnetic resonance imaging. This review explores the pathophysiology of NSCs on ischemic stroke, stem cell therapy studies and their effects on neurogenesis, the most recent clinical trials, and techniques to track and monitor the progress of endogenous and exogenous stem cells.

Current Perspectives Regarding Stem Cell-based Therapy for Ischemic Stroke

2018 ◽  
Vol 24 (28) ◽  
pp. 3332-3340 ◽  
Author(s):  
Kyeong-Ah Kwak ◽  
Ho-Beom Kwon ◽  
Joo Won Lee ◽  
Young-Seok Park
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Time Window ◽  
Experimental Studies ◽  
Cell Type ◽  
Stroke Treatment ◽  
Cell Based Therapy ◽  
Regenerative Approach ◽  
Therapeutic Time Window

Stroke is a leading cause of death and disability worldwide. Conventional treatment has a limitation of very narrow therapeutic time window and its devastating nature necessitate a novel regenerative approach. Transplanted stem cells resulted in functional recovery through multiple mechanisms including neuroprotection, neurogenesis, angiogenesis, immunomodulation, and anti-inflammatory effects. Despite the promising features shown in experimental studies, results from clinical trials are inconclusive from the perspective of efficacy. The present review presents a synopsis of stem cell research on ischemic stroke treatment according to cell type. Clinical trials to the present are briefly summarized. Finally, the hurdles and issues to be solved are discussed for clinical application.

scholarly journals Optimizing Stem Cell Therapy after Ischemic Brain Injury

2020 ◽  
Vol 22 (3) ◽  
pp. 286-305 ◽  
Author(s):  
Shuai Zhang ◽  
Brittany Bolduc Lachance ◽  
Bilal Moiz ◽  
Xiaofeng Jia
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Cardiac Arrest ◽  
Stem Cell ◽  
Brain Injury ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Injury Treatment

Stem cells have been used for regenerative and therapeutic purposes in a variety of diseases. In ischemic brain injury, preclinical studies have been promising, but have failed to translate results to clinical trials. We aimed to explore the application of stem cells after ischemic brain injury by focusing on topics such as delivery routes, regeneration efficacy, adverse effects, and in vivo potential optimization. PUBMED and Web of Science were searched for the latest studies examining stem cell therapy applications in ischemic brain injury, particularly after stroke or cardiac arrest, with a focus on studies addressing delivery optimization, stem cell type comparison, or translational aspects. Other studies providing further understanding or potential contributions to ischemic brain injury treatment were also included. Multiple stem cell types have been investigated in ischemic brain injury treatment, with a strong literature base in the treatment of stroke. Studies have suggested that stem cell administration after ischemic brain injury exerts paracrine effects via growth factor release, blood-brain barrier integrity protection, and allows for exosome release for ischemic injury mitigation. To date, limited studies have investigated these therapeutic mechanisms in the setting of cardiac arrest or therapeutic hypothermia. Several delivery modalities are available, each with limitations regarding invasiveness and safety outcomes. Intranasal delivery presents a potentially improved mechanism, and hypoxic conditioning offers a potential stem cell therapy optimization strategy for ischemic brain injury. The use of stem cells to treat ischemic brain injury in clinical trials is in its early phase; however, increasing preclinical evidence suggests that stem cells can contribute to the down-regulation of inflammatory phenotypes and regeneration following injury. The safety and the tolerability profile of stem cells have been confirmed, and their potent therapeutic effects make them powerful therapeutic agents for ischemic brain injury patients.

Types of Stem Cells Used in US-Based Clinical Trials between 1999 and 2014

2021 ◽  
Vol 26 ◽  
pp. 169-191
Author(s):  
Emma E. Redfield ◽  
Erin K. Luciano ◽  
Monica J. Sewell ◽  
Lucas A. Mitzel ◽  
Isaac J. Sanford ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cell Types ◽  
The Us ◽  
Health Database ◽  
Induced Pluripotent

This study looks at the number of clinical trials involving specific stem cell types. To our knowledge, this has never been done before. Stem cell clinical trials that were conducted at locations in the US and registered on the National Institutes of Health database at ‘clinicaltrials.gov’ were categorized according to the type of stem cell used (adult, cancer, embryonic, perinatal, or induced pluripotent) and the year that the trial was registered. From 1999 to 2014, there were 2,357 US stem cell clinical trials registered on ‘clinicaltrials.gov,’ and 89 percent were from adult stem cells and only 0.12 percent were from embryonic stem cells. This study concludes that embryonic stem cells should no longer be used for clinical study because of their irrelevance, moral questions, and induced pluripotent stem cells.

Stem Cells and Tissue Engineering Techniques

2013 ◽  
Vol 80 (1) ◽  
pp. 11-19
Author(s):  
Gigliola Sica
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Urinary Tract ◽  
Animal Models ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ethical Concerns ◽  
Neoplastic Lesions

The therapeutic use of stem cells and tissue engineering techniques are emerging in urology. Here, stem cell types, their differentiating potential and fundamental characteristics are illustrated. The cancer stem cell hypothesis is reported with reference to the role played by stem cells in the origin, development and progression of neoplastic lesions. In addition, recent reports of results obtained with stem cells alone or seeded in scaffolds to overcome problems of damaged urinary tract tissue are summarized. Among others, the application of these biotechnologies in urinary bladder, and urethra are delineated. Nevertheless, apart from the ethical concerns raised from the use of embryonic stem cells, a lot of questions need to be solved concerning the biology of stem cells before their widespread use in clinical trials. Further investigation is also required in tissue engineering utilizing animal models.

scholarly journals Stem Cell-Derived Extracellular Vesicles for Treating Joint Injury and Osteoarthritis

Nanomaterials ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 261 ◽  
Author(s):  
Jiao Li ◽  
Elham Hosseini-Beheshti ◽  
Georges Grau ◽  
Hala Zreiqat ◽  
Christopher Little
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Joint Injury ◽  
Direct Cell ◽  
Almost All ◽  
New Treatments

Extracellular vesicles (EVs) are nanoscale particles secreted by almost all cell types to facilitate intercellular communication. Stem cell-derived EVs theoretically have the same biological functions as stem cells, but offer the advantages of small size, low immunogenicity, and removal of issues such as low cell survival and unpredictable long-term behaviour associated with direct cell transplantation. They have been an area of intense interest in regenerative medicine, due to the potential to harness their anti-inflammatory and pro-regenerative effects to induce healing in a wide variety of tissues. However, the potential of using stem cell-derived EVs for treating joint injury and osteoarthritis has not yet been extensively explored. The pathogenesis of osteoarthritis, with or without prior joint injury, is not well understood, and there is a longstanding unmet clinical need to develop new treatments that provide a therapeutic effect in preventing or stopping joint degeneration, rather than merely relieving the symptoms of the disease. This review summarises the current evidence relating to stem cell-derived EVs in joint injury and osteoarthritis, providing a concise discussion of their characteristics, advantages, therapeutic effects, limitations and outlook in this exciting new area.

scholarly journals Stem cell therapies for ischemic stroke: current animal models, clinical trials and biomaterials

RSC Advances ◽  
2017 ◽  
Vol 7 (30) ◽  
pp. 18668-18680 ◽  
Author(s):  
Hugh H. Chan ◽  
Connor A. Wathen ◽  
Ming Ni ◽  
Shuangmu Zhuo
Keyword(s):  
Tissue Engineering ◽  
Clinical Trials ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Animal Models ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Stem Cell Therapies ◽  
Cell Therapies

We report the facilitation of stem cell therapy in stroke by tissue engineering and applications of biomaterials.

scholarly journals Neural stem cell transplantation in ischemic stroke: A role for preconditioning and cellular engineering

2017 ◽  
Vol 37 (7) ◽  
pp. 2314-2319 ◽  
Author(s):  
Joshua D Bernstock ◽  
Luca Peruzzotti-Jametti ◽  
Daniel Ye ◽  
Florian A Gessler ◽  
Dragan Maric ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Neural Stem Cell ◽  
Clinical Translation ◽  
Ischemic Brain ◽  
Cellular Therapies ◽  
Beneficial Effects ◽  
The World

Ischemic stroke continues to be a leading cause of morbidity and mortality throughout the world. To protect and/or repair the ischemic brain, a multitiered approach may be centered on neural stem cell (NSC) transplantation. Transplanted NSCs exert beneficial effects not only via structural replacement, but also via immunomodulatory and/or neurotrophic actions. Unfortunately, the clinical translation of such promising therapies remains elusive, in part due to their limited persistence/survivability within the hostile ischemic microenvironment. Herein, we discuss current approaches for the development of NSCs more amenable to survival within the ischemic brain as a tool for future cellular therapies in stroke.

Gene and Stem Cell Therapy in Ischemic Stroke

2009 ◽  
Vol 18 (9) ◽  
pp. 999-1002 ◽  
Author(s):  
Toru Yamashita ◽  
Kentaro Deguchi ◽  
Shoko Nagotani ◽  
Tatsushi Kamiya ◽  
Koji Abe
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Cerebral Ischemia ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Neuroprotective Effect ◽  
Chronic Phase ◽  
Artery Occlusion ◽  
Ischemic Brain ◽  
Gdnf Gene

Possible strategies for treating ischemic stroke include neuroprotection (preventing injured neurons from undergoing apoptosis in the acute phase of cerebral ischemia) and stem cell therapy (the repair of disrupted neuronal networks with newly born neurons in the chronic phase of cerebral ischemia). First, we estimated the neuroprotective effect of glial cell line-derived neurotrophic factor (GDNF) by administration of GFNF protein. GDNF protein showed a direct protective effect against ischemic brain damage. Pretreatment of animals with adenoviral vector containing GDNF gene (Ad-GDNF) 24 h before the subsequent transient middle cerebral artery occlusion (MCAO) effectively reduced infarcted volume. Secondly, we studied the neuroprotective effect of a calcium channel blocker, azelnidipine, or a by-product of heme degradation, biliverdin. Both azelnidipine and biliverdin had a neuroprotective effect in the ischemic brain through their antioxidative property. Lastly, we developed a restorative stroke therapy with a bioaffinitive scaffold, which is able to provide an appropriate platform for newly born neurons. In the future, we will combine these strategies to develop more effective therapies for treatment of strokes.

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