Bioengineering tools to elucidate and control the fate of transplanted stem cells

2014 ◽  
Vol 42 (3) ◽  
pp. 679-687 ◽  
Author(s):  
Rukmani Sridharan ◽  
Jeffrey M. Karp ◽  
Weian Zhao
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Cell Fate ◽  
Stem Cell Therapy ◽  
Search Term ◽  
Cell Therapies ◽  
Cellular Microenvironments ◽  
And Control

For the last decade, stem cell therapies have demonstrated enormous potential for solving some of the most tragic illnesses, diseases and tissue defects worldwide. Currently, more than 1300 clinical trials use stem cell therapy to solve a spectrum of cardiovascular, neurodegenerative and autoimmune diseases (http://www.clinicaltrials.gov, Jan 2014, search term: stem cell therapy; only currently recruiting and completed studies are included in the search). However, the efficacy of stem cell transplantation in patients has not been well established, and recent clinical trials have produced mixed results. We attribute this lack of efficacy in part to an incomplete understanding of the fate of stem cells following transplantation and the lack of control over cell fate, especially cell-homing and therapeutic functions. In the present review, we present two of our recently developed technologies that aim to address the above-mentioned bottlenecks in stem cell therapy specifically in the areas of MSCs (mesenchymal stem cells): (i) aptamer-based cell-surface sensors to study cellular microenvironments, and (ii) mRNA engineering technology to enhance the homing and immunomodulatory efficacy of transplanted stem cells. The first engineering strategy aims to elucidate the basic cellular signalling that occurs in the microenvironment of transplanted stem cells in real time. The second technique involves a simple mRNA transfection that improves the homing and anti-inflammatory capability of MSCs. Although we have specifically applied these engineering techniques to MSCs, these strategies can be incorporated for almost any cell type to determine and control the fate of transplanted stem cells.

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.

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.

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 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 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 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 Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Qi Zhang ◽  
Xin-xing Wan ◽  
Xi-min Hu ◽  
Wen-juan Zhao ◽  
Xiao-xia Ban ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Programmed Cell Death ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Effects ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Wide Range

Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.

scholarly journals Effects of nicotine on the translation of stem cell therapy

2020 ◽  
Vol 15 (5) ◽  
pp. 1679-1688
Author(s):  
Alex HP Chan ◽  
Ngan F Huang
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Therapeutic Potential ◽  
Electronic Cigarettes ◽  
Nicotine Exposure ◽  
Cell Therapies ◽  
Lifestyle Choices

Although stem cell therapy has tremendous therapeutic potential, clinical translation of stem cell therapy has yet to be fully realized. Recently, patient comorbidities and lifestyle choices have emerged to be important factors in the efficacy of stem cell therapy. Tobacco usage is an important risk factor for numerous diseases, and nicotine exposure specifically has become increasing more prevalent with the rising use of electronic cigarettes. This review describes the effects of nicotine exposure on the function of various stem cells. We place emphasis on the differential effects of nicotine exposure in vitro and as well as in preclinical models. Further research on the effects of nicotine on stem cells will deepen our understanding of how lifestyle choices can impact the outcome of stem cell therapies.

scholarly journals Cardiomyocyte Death and Genome-Edited Stem Cell Therapy for Ischemic Heart Disease

2021 ◽  
Author(s):  
Hyun-Min Cho ◽  
Je-Yoel Cho
Keyword(s):  
Stem Cells ◽  
Cell Death ◽  
Stem Cell ◽  
Heart Disease ◽  
Cell Therapy ◽  
Ischemic Heart Disease ◽  
Genome Editing ◽  
Stem Cell Therapy ◽  
Stem Cell Therapies ◽  
Cell Therapies

AbstractMassive death of cardiomyocytes is a major feature of cardiovascular diseases. Since the regenerative capacity of cardiomyocytes is limited, the regulation of their death has been receiving great attention. The cell death of cardiomyocytes is a complex mechanism that has not yet been clarified, and it is known to appear in various forms such as apoptosis, necrosis, etc. In ischemic heart disease, the apoptosis and necrosis of cardiomyocytes appear in two types of programmed forms (intrinsic and extrinsic pathways) and they account for a large portion of cell death. To repair damaged cardiomyocytes, diverse stem cell therapies have been attempted. However, despite the many positive effects, the low engraftment and survival rates have clearly limited the application of stem cells in clinical therapy. To solve these challenges, the introduction of the desired genes in stem cells can be used to enhance their capacity and improve their therapeutic efficiency. Moreover, as genome engineering technologies have advanced significantly, safer and more stable delivery of target genes and more accurate deletion of genes have become possible, which facilitates the genetic modification of stem cells. Accordingly, stem cell therapy for damaged cardiac tissue is expected to further improve. This review describes myocardial cell death, stem cell therapy for cardiac repair, and genome-editing technologies. In addition, we introduce recent stem cell therapies that incorporate genome-editing technologies in the myocardial infarction model.

scholarly journals Surfing the clinical trials of mesenchymal stem cell therapy in ischemic cardiomyopathy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Iman Razeghian-Jahromi ◽  
Anthony G. Matta ◽  
Ronan Canitrot ◽  
Mohammad Javad Zibaeenezhad ◽  
Mahboobeh Razmkhah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Clinical Practice ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ischemic Cardiomyopathy ◽  
Reverse Remodeling ◽  
Paracrine Factors

AbstractWhile existing remedies failed to fully address the consequences of heart failure, stem cell therapy has been introduced as a promising approach. The present review is a comprehensive appraisal of the impacts of using mesenchymal stem cells (MSCs) in clinical trials mainly conducted on ischemic cardiomyopathy. The benefits of MSC therapy for dysfunctional myocardium are likely attributed to numerous secreted paracrine factors and immunomodulatory effects. The positive outcomes associated with MSC therapy are scar size reduction, reverse remodeling, and angiogenesis. Also, a decreasing in the level of chronic inflammatory markers of heart failure progression like TNF-α is observed. The intense inflammatory reaction in the injured myocardial micro-environment predicts a poor response of scar tissue to MSC therapy. Subsequently, the interval delay between myocardial injury and MSC therapy is not yet determined. The optimal requested dose of cells ranges between 100 to 150 million cells. Allogenic MSCs have different advantages compared to autogenic cells and intra-myocardial injection is the preferred delivery route. The safety and efficacy of MSCs-based therapy have been confirmed in numerous studies, however several undefined parameters like route of administration, optimal timing, source of stem cells, and necessary dose are limiting the routine use of MSCs therapeutic approach in clinical practice. Lastly, pre-conditioning of MSCs and using of exosomes mediated MSCs or genetically modified MSCs may improve the overall therapeutic effect. Future prospective studies establishing a constant procedure for MSCs transplantation are required in order to apply MSC therapy in our daily clinical practice and subsequently improving the overall prognosis of ischemic heart failure patients.

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