scholarly journals Transplantation Site Affects the Outcomes of Adipose-Derived Stem Cell-Based Therapy for Retinal Degeneration

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Chengyu Hu ◽  
Huanzhi La ◽  
Xuancheng Wei ◽  
Yue Zhou ◽  
Qingjian Ou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Neural Retina ◽  
Rosette Formation ◽  
Subretinal Space ◽  
Electric Response ◽  
Anatomic Structure ◽  
Cell Based Therapy ◽  
Transplantation Site

Adipose-derived stem cells (ASCs) have shown a strong protective effect on retinal degenerative diseases (RDD) after being transplanted into the subretinal space in an animal model. Recently, several clinical trials have been conducted to treat RDD with intravitreal transplantation of stem cells, including ASCs. However, the outcomes of the clinical trials were not satisfactory. To investigate if the transplantation site alters the outcome of stem cell-based therapy for RDD, we isolated rat ASCs (rASCs) and labeled them with green fluorescent protein. Autologous rASCs were grafted into the vitreous chamber or subretinal space in a rat RDD model induced by sodium iodate (SI). The electric response was recorded by ERG. The anatomic structure of the retina was observed in cryosections of rat eyes at posttransplantation weeks 1, 2, and 4. Neural retina apoptosis and epiretinal membrane- (ERM-) like structure formation were investigated by immunostaining. The intravitreal transplantation of rASCs resulted in an extinguished electric response, although the rosette formation and apoptosis of neural retina were reduced. However, the rASCs that grafted in the subretinal space protected the retina from the damage caused by SI, including a partial recovering of the electric response and a reduction in rosette formation. Intravitreally grafted rASCs formed a membrane, resulting in retina folding at the injection site. Müller cells, retinal pigment epithelial cells, and microglial cells migrated from the retina to the rASC-formed membrane and subsequently formed an ERM-like structure. Furthermore, vitreous fluid promoted rASC migration, and rASC-conditioned medium enhanced Müller cell migration as indicated by in vitro studies. These data suggested that the vitreous chamber is not a good transplantation site for ASC-based therapy for RDD and that a deliberate decision should be made before transplantation of stem cells into the vitreous chamber to treat RDD in clinical trials.

scholarly journals Induced Pluripotent Stem Cells: Hope in the Treatment of Diseases, including Muscular Dystrophies

2020 ◽  
Vol 21 (15) ◽  
pp. 5467
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Cynthia Machado Cascabulho ◽  
Luiz Anastácio Alves ◽  
Andrea Henriques-Pons
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Ips Cells ◽  
High Plasticity ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Induced pluripotent stem (iPS) cells are laboratory-produced cells that combine the biological advantages of somatic adult and stem cells for cell-based therapy. The reprogramming of cells, such as fibroblasts, to an embryonic stem cell-like state is done by the ectopic expression of transcription factors responsible for generating embryonic stem cell properties. These primary factors are octamer-binding transcription factor 4 (Oct3/4), sex-determining region Y-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and the proto-oncogene protein homolog of avian myelocytomatosis (c-Myc). The somatic cells can be easily obtained from the patient who will be subjected to cellular therapy and be reprogrammed to acquire the necessary high plasticity of embryonic stem cells. These cells have no ethical limitations involved, as in the case of embryonic stem cells, and display minimal immunological rejection risks after transplant. Currently, several clinical trials are in progress, most of them in phase I or II. Still, some inherent risks, such as chromosomal instability, insertional tumors, and teratoma formation, must be overcome to reach full clinical translation. However, with the clinical trials and extensive basic research studying the biology of these cells, a promising future for human cell-based therapies using iPS cells seems to be increasingly clear and close.

Moral obligations in conducting stem cell-based therapy trials for autism spectrum disorder

2021 ◽  
pp. medethics-2020-107106
Author(s):  
Nicole Shu Ling Yeo-Teh ◽  
Bor Luen Tang
Keyword(s):  
Autism Spectrum Disorder ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Therapeutic Benefit ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Moral Obligations ◽  
Direct To Consumer ◽  
Cell Based Therapy

Unregulated patient treatments and approved clinical trials have been conducted with haematopoietic stem cells and mesenchymal stem cells for children with autism spectrum disorder (ASD). While the former direct-to-consumer practice is usually considered rogue and should be legally constrained, regulated clinical trials could also be ethically questionable. Here, we outline principal objections against these trials as they are currently conducted. Notably, these often lack a clear rationale for how transplanted cells may confer a therapeutic benefit in ASD, and thus, have ill-defined therapeutic outcomes. We posit that ambiguous and unsubstantiated descriptions of outcome from such clinical trials may nonetheless appeal to the lay public as being based on authentic scientific findings. These may further fuel caregivers of patients with ASD to pursue unregulated direct-to-consumer treatments, thus exposing them to unnecessary risks. There is, therefore, a moral obligation on the part of those regulating and conducting clinical trials of stem cell-based therapeutic for ASD minors to incorporate clear therapeutic targets, scientific rigour and reporting accuracy in their work. Any further stem cell-based trials for ASD unsupported by significant preclinical advances and particularly sound scientific hypothesis and aims would be ethically indefensible.

scholarly journals Stem cell-based therapy for COVID-19 and ARDS: a systematic review

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gabriele Zanirati ◽  
Laura Provenzi ◽  
Lucas Lobraico Libermann ◽  
Sabrina Comin Bizotto ◽  
Isadora Machado Ghilardi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Cell Therapy ◽  
Clinical Studies ◽  
Case Series ◽  
Potential Candidate ◽  
Phase I Clinical Trials ◽  
Cell Based Therapy

AbstractDespite global efforts to establish effective interventions for coronavirus disease 2019 (COVID-19) and its major complications, such as acute respiratory distress syndrome (ARDS), the treatment remains mainly supportive. Hence, identifying an effective and safe therapy for severe COVID-19 is critical for saving lives. A significant number of cell-based therapies have been through clinical investigation. In this study, we performed a systematic review of clinical studies investigating different types of stem cells as treatments for COVID-19 and ARDS to evaluate the safety and potential efficacy of cell therapy. The literature search was performed using PubMed, Embase, and Scopus. Among the 29 studies, there were eight case reports, five Phase I clinical trials, four pilot studies, two Phase II clinical trials, one cohort, and one case series. Among the clinical studies, 21 studies used cell therapy to treat COVID-19, while eight studies investigated cell therapy as a treatment for ARDS. Most of these (75%) used mesenchymal stem cells (MSCs) to treat COVID-19 and ARDS. Findings from the analyzed articles indicate a positive impact of stem cell therapy on crucial immunological and inflammatory processes that lead to lung injury in COVID-19 and ARDS patients. Additionally, among the studies, there were no reported deaths causally linked to cell therapy. In addition to standard care treatments concerning COVID-19 management, there has been supportive evidence towards adjuvant therapies to reduce mortality rates and improve recovery of care treatment. Therefore, MSCs treatment could be considered a potential candidate for adjuvant therapy in moderate-to-severe COVID-19 cases and compassionate use.

scholarly journals Stem Cell Therapy for Chronic Pain Management: Review of Uses, Advances, and Adverse Effects

2017 ◽  
Vol 4 (20;4) ◽  
pp. 293-305 ◽  
Author(s):  
Krishnan Chakravarthy
Keyword(s):  
Stem Cells ◽  
Chronic Pain ◽  
Clinical Trials ◽  
Neuropathic Pain ◽  
Stem Cell ◽  
Pain Management ◽  
Cell Therapy ◽  
Treatment Modalities ◽  
Chronic Pain Management ◽  
Cell Based Therapy

Background: This review article outlines the recent advances, uses, and adverse effects of cell-based therapy for chronic pain management. Cell based therapies are gaining increasing ground as novel treatment modalities for a variety of pain pathologies that include, but are not limited to, neuropathic pain and degenerative disc disease. As these treatment modalities become more common practice, we have focused our review to provide pain practitioners and other practicing physicians an understanding of the technology and to summarize key clinical data and existing clinical trials that are being pursued by clinical investigators worldwide. Objective: Review of stem cell technology and applications in pain management. Study Design: Narrative review. Methods: The Pubmed NCBI and EMBASE databases was utilized to review published reports of clinical studies reported from 2000 to 2015, and ClinicalTrials.gov (www. clinicaltrials.gov/ct2/search) search function was used to document ongoing clinical trials [keywords: “chronic pain,” “disc pain,” “cell therapy,” “osteoarthritis,” “neuropathic,” “stem cell”] currently active and recruiting patients. Results: Articles were screened by title, abstract, and full article review. They were then analyzed by specific clinical indications and appropriate data were presented based on critical analysis of those articles. Limitations: More studies looking at the systematic use of stem cells in pain management will be required to draw conclusions about the benefits of the technology. Conclusion: Though the data from existing studies look promising for the use of stem cells as a novel therapeutic strategy for discogenic pain, neuropathic pain, and osteoarthritis, additional clinical studies will be needed to validate the benefit of the technology for clinical use. However, we hope that this narrative review will help guide pain physicians in making informed decisions for their patients about the potential of cell-based therapy for treating chronic pain conditions. Key words: Stem cell therapy, chronic pain, clinical trials, disc pain, neuropathic pain, mesenchymal stem cells, osteoarthritis, pain management

scholarly journals Traumatic Brain Injury and Stem Cells: An Overview of Clinical Trials, the Current Treatments and Future Therapeutic Approaches

Medicina ◽  
2020 ◽  
Vol 56 (3) ◽  
pp. 137 ◽  
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Traumatic Brain Injury ◽  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Brain Injury ◽  
Brain Damage ◽  
Physical Damage ◽  
Safety And Efficacy ◽  
Cell Based Therapy ◽  
The Brain

Traumatic brain injury represents physical damage to the brain tissue that induces transitory or permanent neurological disabilities. The traumatic injury activates an important inflammatory response, followed by a cascade of events that lead to neuronal loss and further brain damage. Maintaining proper ventilation, a normal level of oxygenation, and adequate blood pressure are the main therapeutic strategies performed after injury. Surgery is often necessary for patients with more serious injuries. However, to date, there are no therapies that completely resolve the brain damage suffered following the trauma. Stem cells, due to their capacity to differentiate into neuronal cells and through releasing neurotrophic factors, seem to be a valid strategy to use in the treatment of traumatic brain injury. The purpose of this review is to provide an overview of clinical trials, aimed to evaluate the use of stem cell-based therapy in traumatic brain injury. These studies aim to assess the safety and efficacy of stem cells in this disease. The results available so far are few; therefore, future studies need in order to evaluate the safety and efficacy of stem cell transplantation in traumatic brain injury.

scholarly journals Stem Cells Therapy for Spinal Cord Injury: An Overview of Clinical Trials

2020 ◽  
Vol 21 (2) ◽  
pp. 659 ◽  
Author(s):  
Serena Silvestro ◽  
Placido Bramanti ◽  
Oriana Trubiani ◽  
Emanuela Mazzon
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Stem Cell ◽  
Experimental Studies ◽  
Motor Deficits ◽  
Safety And Efficacy ◽  
Cell Based Therapy ◽  
Cord Injury

Spinal cord injury (SCI) is a traumatic lesion that causes disability with temporary or permanent sensory and/or motor deficits. The pharmacological approach still in use for the treatment of SCI involves the employment of corticosteroid drugs. However, SCI remains a very complex disorder that needs future studies to find effective pharmacological treatments. SCI actives a strong inflammatory response that induces a loss of neurons followed by a cascade of events that lead to further spinal cord damage. Many experimental studies demonstrate the therapeutic effect of stem cells in SCI due to their capacity to differentiate into neuronal cells and by releasing neurotrophic factors. Therefore, they appear to be a valid strategy to use in the field of regenerative medicine. The purpose of this paper is to provide an overview of clinical trials, recorded in clinical trial.gov during 2005–2019, aimed to evaluate the use of stem cell-based therapy in SCI. The results available thus far show the safety and efficacy of stem cell therapy in patients with SCI. However, future trials are needed to investigate the safety and efficacy of stem cell transplantation.

scholarly journals Perspective on Stem Cell Therapy in Organ Fibrosis: Animal Models and Human Studies

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1068
Author(s):  
Joanna Wiśniewska ◽  
Agnieszka Sadowska ◽  
Anna Wójtowicz ◽  
Magda Słyszewska ◽  
Anna Szóstek-Mioduchowska
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Animal Models ◽  
The Body ◽  
Preclinical Studies ◽  
Cell Based Therapy ◽  
Fibrotic Diseases ◽  
Fibrotic Disorders ◽  
Organ Fibrosis

Tissue fibrosis is characterized by excessive deposition of extracellular matrix (ECM) components that result from the disruption of regulatory processes responsible for ECM synthesis, deposition, and remodeling. Fibrosis develops in response to a trigger or injury and can occur in nearly all organs of the body. Thus, fibrosis leads to severe pathological conditions that disrupt organ architecture and cause loss of function. It has been estimated that severe fibrotic disorders are responsible for up to one-third of deaths worldwide. Although intensive research on the development of new strategies for fibrosis treatment has been carried out, therapeutic approaches remain limited. Since stem cells, especially mesenchymal stem cells (MSCs), show remarkable self-renewal, differentiation, and immunomodulatory capacity, they have been intensively tested in preclinical studies and clinical trials as a potential tool to slow down the progression of fibrosis and improve the quality of life of patients with fibrotic disorders. In this review, we summarize in vitro studies, preclinical studies performed on animal models of human fibrotic diseases, and recent clinical trials on the efficacy of allogeneic and autologous stem cell applications in severe types of fibrosis that develop in lungs, liver, heart, kidney, uterus, and skin. Although the results of the studies seem to be encouraging, there are many aspects of cell-based therapy, including the cell source, dose, administration route and frequency, timing of delivery, and long-term safety, that remain open areas for future investigation. We also discuss the contemporary status, challenges, and future perspectives of stem cell transplantation for therapeutic options in fibrotic diseases as well as we present recent patents for stem cell-based therapies in organ fibrosis.

scholarly journals Preclinical efficacy of stem cell therapy for skin flap: a systematic review and meta-analysis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan Li ◽  
Qi-lin Jiang ◽  
Leanne Van der Merwe ◽  
Dong-hao Lou ◽  
Cai Lin
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Stem Cell ◽  
Survival Rate ◽  
Meta Analysis ◽  
Skin Flap ◽  
Cochrane Library ◽  
Skin Flaps ◽  
Cell Based Therapy ◽  
Stem Cell Treatment

Abstract Background A skin flap is one of the most critical surgical techniques for the restoration of cutaneous defects. However, the distal necrosis of the skin flap severely restricts the clinical application of flap surgery. As there is no consensus on the treatment methods to prevent distal necrosis of skin flaps, more effective and feasible interventions to prevent skin flaps from necrosis are urgently needed. Stem therapy as a potential method to improve the survival rate of skin flaps is receiving increasing attention. Methods This review followed the recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statements. Twenty studies with 500 animals were included by searching Web of Science, EMBASE, PubMed, and Cochrane Library databases, up until October 8, 2020. Moreover, the references of the included articles were searched manually to obtain other studies. All analyses were conducted using Review Manager V.5.3 software. Results Meta-analysis of all 20 studies demonstrated stem cell treatment has significant effects on reducing necrosis of skin flap compared with the control group (SMD: 3.20, 95% CI 2.47 to 3.93). Besides, subgroup analysis showed differences in the efficacy of stem cells in improving the survival rate of skin flaps in areas of skin flap, cell type, transplant types, and method of administration of stem cells. The meta-analysis also showed that stem cell treatment had a significant effect on increasing blood vessel density (SMD: 2.96, 95% CI 2.21 to 3.72) and increasing the expression of vascular endothelial growth factor (VEGF, SMD: 4.34, 95% CI 2.48 to 6.1). Conclusions The preclinical evidence of our systematic review indicate that stem cell-based therapy is effective for promoting early angiogenesis by up regulating VEGF and ultimately improving the survival rate of skin flap. In summary, small area skin flap, the administration method of intra-arterial injection, ASCs and MSCs, and xenogenic stem cells from humans showed more effective for the survival of animal skin flaps. In general, stem cell-based therapy may be a promising method to prevent skin flap necrosis.

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.

Amniotic Stem Cell-Conditioned Media for the Treatment of Nerve and Muscle Pathology: A Systematic Review

2021 ◽  
Author(s):  
Chukwuweike Gwam ◽  
Ahmed Emara ◽  
Nequesha Mohamed ◽  
Noor Chughtai ◽  
Johannes Plate ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Regeneration ◽  
Cell Damage ◽  
Conditioned Media ◽  
Nerve Tissue ◽  
Muscle Pathology ◽  
Loss Of Function ◽  
Cell Based Therapy

Muscle and nerve tissue damage can elicit a significant loss of function and poses as a burden for patients and healthcare providers. Even for tissues, such as the peripheral nerve and skeletal muscle, that harbor significant regenerative capacity, innate regenerative processes often lead to less than optimal recovery and residual loss of function. The reasons for poor regeneration include significant cell damage secondary to oxidative stress, poor recruitment of resident stem cells, and an unfavorable microenvironment for tissue regeneration. Stem cell-based therapy was once thought as a potential therapy in tissue regeneration, due to its self-renewal and multipotent capabilities. Early advocates for cellular-based therapy pointed to the pluripotent nature of stem cells, thus eluding to its ability to differentiate into resident cells as the source of its regenerative capability. However, increasing evidence has revealed a lack of engraftment and differentiation of stem cells, thereby pointing to stem cell paracrine activity as being responsible for its regenerative potential. Stem cell-conditioned media houses biomolecular factors that portray significant regenerative potential. Amniotic-derived stem cell-conditioned media (AFS-CM) has been of particular interest because of its ease of allocation and in vitro culture. The purpose of this review is to report the results of studies that assess the role of AFS-CM for nerve and muscle conditions. In this review, we will cover the effects of AFS-CM on cellular pathways, genes, and protein expression for different nerve and muscle cell types.

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