Microphysiological stroke model for systematic evaluation of neurorestorative potential of stem cell therapy

2021 ◽  
Author(s):  
Wonjae Lee ◽  
Zhonlin Lyu ◽  
Jon Park ◽  
Kwang-Min Kim ◽  
Hye-jin Jin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Neurological Function ◽  
Systematic Evaluation

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.

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

2021 ◽  
Vol 9 ◽  
Author(s):  
Guoyang Zhou ◽  
Yongjie Wang ◽  
Shiqi Gao ◽  
Xiongjie Fu ◽  
Yang Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Protective Factor ◽  
Neural Circuit ◽  
Chronic Phase ◽  
Cell Types ◽  
Stroke Treatment

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.

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.

Abstract TP401: Inflated Expectations about Stem Cell Therapy in Patients With Chronic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Jinho Lee ◽  
Kyu-Yong Lee ◽  
Young-Seo Kim ◽  
Hyun Young Kim ◽  
Hyuk Sung Kwon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Ischemic Stroke ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Chronic Stroke ◽  
Accurate Information ◽  
Stroke Patients ◽  
Media Channels ◽  
Source Of Information

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.

scholarly journals Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yanhong Zhang ◽  
Honghong Yao
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Noncoding Rna ◽  
Image Resolution ◽  
Cell Labeling ◽  
Stroke Treatment ◽  
Therapeutic Mechanisms

Stem cell therapy is a promising potential therapeutic strategy to treat cerebral ischemia in preclinical and clinical trials. Currently proposed treatments for stroke employing stem cells include the replacement of lost neurons and integration into the existing host circuitry, the release of growth factors to support and promote endogenous repair processes, and the secretion of extracellular vesicles containing proteins, noncoding RNA, or DNA to regulate gene expression in recipient cells and achieve immunomodulation. Progress has been made to elucidate the precise mechanisms underlying stem cell therapy and the homing, migration, distribution, and differentiation of transplanted stem cells in vivo using various imaging modalities. Noninvasive and safe tracer agents with high sensitivity and image resolution must be combined with long-term monitoring using imaging technology to determine the optimal therapy for stroke in terms of administration route, dosage, and timing. This review discusses potential therapeutic mechanisms of stem cell transplantation for the treatment of stroke and the limitations of current therapies. Methods to label transplanted cells and existing imaging systems for stem cell labeling and in vivo tracking will also be discussed.

scholarly journals Journey of Mesenchymal Stem Cells for Homing: Strategies to Enhance Efficacy and Safety of Stem Cell Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sung Keun Kang ◽  
Il Seob Shin ◽  
Myung Soon Ko ◽  
Jung Youn Jo ◽  
Jeong Chan Ra
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Human Mesenchymal Stem Cells ◽  
Cellular Damage ◽  
Efficacy And Safety ◽  
Clinical Benefits

Human mesenchymal stem cells (MSCs) communicate with other cells in the human body and appear to “home” to areas of injury in response to signals of cellular damage, known as homing signals. This review of the state of current research on homing of MSCs suggests that favorable cellular conditions and thein vivoenvironment facilitate and are required for the migration of MSCs to the site of insult or injuryin vivo. We review the current understanding of MSC migration and discuss strategies for enhancing both the environmental and cellular conditions that give rise to effective homing of MSCs. This may allow MSCs to quickly find and migrate to injured tissues, where they may best exert clinical benefits resulting from improved homing and the presence of increased numbers of MSCs.

scholarly journals Diabetic Retinopathy and Stem Cell Therapy

2021 ◽  
Author(s):  
Sevil Kestane
Keyword(s):  
Stem Cells ◽  
Diabetic Retinopathy ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Treatment Strategies ◽  
Cell Therapies ◽  
Long Time

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.

scholarly journals Treating Metastatic Brain Cancers With Stem Cells

2021 ◽  
Vol 14 ◽  
Author(s):  
Nadia Sadanandan ◽  
Alex Shear ◽  
Beverly Brooks ◽  
Madeline Saft ◽  
Dorothy Anne Galang Cabantan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Brain Metastases ◽  
Stem Cell Therapy ◽  
Brain Cancer ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Neurovascular Unit ◽  
Advantages And Disadvantages

Stem cell therapy may present an effective treatment for metastatic brain cancer and glioblastoma. Here we posit the critical role of a leaky blood-brain barrier (BBB) as a key element for the development of brain metastases, specifically melanoma. By reviewing the immunological and inflammatory responses associated with BBB damage secondary to tumoral activity, we identify the involvement of this pathological process in the growth and formation of metastatic brain cancers. Likewise, we evaluate the hypothesis of regenerating impaired endothelial cells of the BBB and alleviating the damaged neurovascular unit to attenuate brain metastasis, using the endothelial progenitor cell (EPC) phenotype of bone marrow-derived mesenchymal stem cells. Specifically, there is a need to evaluate the efficacy for stem cell therapy to repair disruptions in the BBB and reduce inflammation in the brain, thereby causing attenuation of metastatic brain cancers. To establish the viability of stem cell therapy for the prevention and treatment of metastatic brain tumors, it is crucial to demonstrate BBB repair through augmentation of vasculogenesis and angiogenesis. BBB disruption is strongly linked to metastatic melanoma, worsens neuroinflammation during metastasis, and negatively influences the prognosis of metastatic brain cancer. Using stem cell therapy to interrupt inflammation secondary to this leaky BBB represents a paradigm-shifting approach for brain cancer treatment. In this review article, we critically assess the advantages and disadvantages of using stem cell therapy for brain metastases and glioblastoma.

scholarly journals A REPORT ON STEM CELLS AND THEIR APPLICATIONS

2020 ◽  
pp. 1-2
Author(s):  
Shantha A R
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Building Blocks ◽  
Cell Types ◽  
The Body ◽  
Cell Therapies ◽  
Undifferentiated Cells ◽  
The Cost

Stem cells are the building blocks of life. They have remarkable potential to regenerate and develop into many different cell types in the body during early life and growth. They are also a class of undifferentiated cells that are able to be differentiated into specialized cells types. Stem cells are characterized by certain features such as totipotency, pluripotency, multipotency, oligopotent and unipotency. The history of stem cell research had an embryonic beginning in the mid 1800s with the discovery that few cells could generate other cells. In the 1900s the first stem cells were discovered when it was found that cells generate blood cells. Nowadays, stem cell therapy is under research and till now, a very few stem cell therapies have been regarded as safe and successful. It is also found that stem cell therapy cast a number of side effects too. The cost of the procedure too is expensive and is not easily affordable.

scholarly journals Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Boxian Huang ◽  
Chunfeng Qian ◽  
Chenyue Ding ◽  
Qingxia Meng ◽  
Qinyan Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ovarian Function ◽  
Ovarian Insufficiency ◽  
Apoptotic Genes

Abstract Background With the development of regenerative medicine and tissue engineering technology, almost all stem cell therapy is efficacious for the treatment of premature ovarian failure (POF) or premature ovarian insufficiency (POI) animal models, whereas little stem cell therapy has been practiced in clinical settings. The underlying molecular mechanism and safety of stem cell treatment in POI are not fully understood. In this study, we explored whether fetal mesenchymal stem cells (fMSCs) from the liver restore ovarian function and whether melatonin membrane receptor 1 (MT1) acts as a regulator for treating POI disease. Methods We designed an in vivo model (chemotherapy-induced ovary damage) and an in vitro model (human ovarian granulosa cells (hGCs)) to understand the efficacy and molecular cues of fMSC treatment of POI. Follicle development was observed by H&E staining. The concentration of sex hormones in serum (E2, AMH, and FSH) and the concentration of oxidative and antioxidative metabolites and the enzymes MDA, SOD, CAT, LDH, GR, and GPx were measured by ELISA. Flow cytometry (FACS) was employed to detect the percentages of ROS and proliferation rates. mRNA and protein expression of antiapoptotic genes (SURVIVIN and BCL2), apoptotic genes (CASPASE-3 and CASPASE-9), and MT1 and its downstream genes (JNK1, PCNA, AMPK) were tested by qPCR and western blotting. MT1 siRNA and related antagonists were used to assess the mechanism. Results fMSC treatment prevented cyclophosphamide (CTX)-induced follicle loss and recovered sex hormone levels. Additionally, fMSCs significantly decreased oxidative damage, increased oxidative protection, improved antiapoptotic effects, and inhibited apoptotic genes in vivo and in vitro. Furthermore, fMSCs also upregulated MT1, JNK1, PCNA, and AMPK at the mRNA and protein levels. With MT1 knockdown or antagonist treatment in normal hGCs, the protein expression of JNK1, PCNA, and AMPK and the percentage of proliferation were impaired. Conclusions fMSCs might play a crucial role in mediating follicular development in the POI mouse model and stimulating the activity of POI hGCs by targeting MT1.

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.

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