scholarly journals New trends in cellular therapy

Development ◽  
2020 ◽  
Vol 147 (18) ◽  
pp. dev192567 ◽  
Author(s):  
Hideyuki Okano ◽  
Doug Sipp

ABSTRACTRegenerative therapies, including both gene and cellular therapies, aim to induce regeneration of cells, tissues and organs and restore their functions. In this short Spotlight, we summarize the latest advances in cellular therapies using pluripotent stem cells (PSCs), highlighting the current status of clinical trials using induced (i)PSC-derived cells. We also discuss the different cellular products that might be used in clinical studies, and consider safety issues and other challenges in iPSC-based cell therapy.

2008 ◽  
Vol 24 (3-4) ◽  
pp. E18 ◽  
Author(s):  
Matthew T. Harting ◽  
James E. Baumgartner ◽  
Laura L. Worth ◽  
Linda Ewing-Cobbs ◽  
Adrian P. Gee ◽  
...  

Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.


2019 ◽  
Vol 81 (1) ◽  
pp. 335-357 ◽  
Author(s):  
Melissa H. Little ◽  
Lorna J. Hale ◽  
Sara E. Howden ◽  
Santhosh V. Kumar

Human kidney tissue can now be generated via the directed differentiation of human pluripotent stem cells. This advance is anticipated to facilitate the modeling of human kidney diseases, provide platforms for nephrotoxicity screening, enable cellular therapy, and potentially generate tissue for renal replacement. All such applications will rely upon the accuracy and reliability of the model and the capacity for stem cell–derived kidney tissue to recapitulate both normal and diseased states. In this review, we discuss the models available, how well they recapitulate the human kidney, and how far we are from application of these cells for use in cellular therapies.


StemJournal ◽  
2021 ◽  
pp. 1-11
Author(s):  
Dinesh Boopalan ◽  
Ramanan Pandian ◽  
Gokul Kesavan

Stem cells offer a promising therapeutic strategy to not only treat several incurable diseases but also regenerate damaged tissues. The current global boom in the field of stem cell and regenerative therapies had led to India becoming a global hotspot for stem cell-based therapies. In this review, we assess the current status of stem cell therapy trials in India and show that the bone marrow-derived stem cells, like mesenchymal stem/stromal cells (MSCs), are predominantly used. Phase 1 and 2 clinical trials have also used MSCs to alleviate symptoms of severe novel coronavirus infections. Recent breakthroughs in gene editing technologies, combined with stem cell therapy, can be effectively harnessed to devise large-scale and affordable treatments for haematological diseases that are highly prevalent in India, like beta-thalassemia and sickle cell diseases. Innovations in stem cell therapy in India can make treatments more affordable to address the needs of in-country patients.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gabriele Zanirati ◽  
Laura Provenzi ◽  
Lucas Lobraico Libermann ◽  
Sabrina Comin Bizotto ◽  
Isadora Machado Ghilardi ◽  
...  

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.


2020 ◽  
Vol 136 (1) ◽  
pp. 127-141
Author(s):  
Sheeba Khan ◽  
Reenam S Khan ◽  
Philip N Newsome

Abstract Introduction Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact. Data sources A literature review was carried out using Pubmed. Keywords used for search were ‘ATMP’, ‘immune mediated’, ‘autoimmune liver disease’ and ‘immune mediated gastrointestinal conditions’, ‘cell therapy’, ‘MSC’, ‘HSCT’, ‘Regulatory T cells’, ‘GVHD’, ‘Coeliac disease’ ‘IBD’, ‘PSC’, ‘AIH’, ‘PBC’. No new data were generated or analysed in support of this review. Areas of agreement There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to ‘reset’ the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications. Areas of controversy There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data. Growing points MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies. Areas timely for developing research Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further.


Neurosurgery ◽  
2020 ◽  
Author(s):  
Ben Jiahe Gu ◽  
David K Kung ◽  
Han-Chiao Isaac Chen

Abstract Cell therapy has been widely recognized as a promising strategy to enhance recovery in stroke survivors. However, despite an abundance of encouraging preclinical data, successful clinical translation remains elusive. As the field continues to advance, it is important to reexamine prior clinical trials in the context of their intended mechanisms, as this can inform future preclinical and translational efforts. In the present work, we review the major clinical trials of cell therapy for stroke and highlight a mechanistic shift between the earliest studies, which aimed to replace dead and damaged neurons, and later ones that focused on exploiting the various neuromodulatory effects afforded by stem cells. We discuss why both mechanisms are worth pursuing and emphasize the means through which cell replacement can still be achieved.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A995-A995
Author(s):  
Sarah Church ◽  
Christina Bailey ◽  
Sarah Warren ◽  
Lisa Butterfield

BackgroundThe field of cellular therapy remains one of the most promising areas for the development of new cancer treatments. To further these improvements, it is imperative to broadly understand cell therapy products at the molecular level and to identify factors that contribute to their efficacy. NanoString and the Parker Institute for Cancer Immunotherapy (PICI) have established a ground-breaking collaboration to characterize up to 1,000 apheresis and cellular therapy infusion products with the primary goal to dissect and study molecular pathways that correlate with optimal cellular therapies.MethodsUsing a large and diverse sample cohort collected from eight PICI network Cell Therapy Centers the team will aim to study gene expression profiles (GEP) that correlate with optimal apheresis and downstream cellular products, identifying biomarkers and signatures for clinical response or toxicity and further explore unique cancer-specific and shared characteristics that make an optimal and effective chimeric antigen receptor (CAR) T cell. As shown here, this first of its kind study will include samples that target dozens of different antigens covering both primary and metastatic hematological and solid tumors. Samples will be characterized using the standardized set of genes included in the nCounter CAR-T Characterization Panel and will measure essential components of CAR-T including: metabolic fitness, phenotype, TCR diversity, toxicity, activation, persistence, exhaustion and cell typing along with individual transgene expression.ResultsPresented here are initial questions that will be asked as part of this study. Meta-analysis will be performed as an aggregated set of data and individual site-specific analysis. Data will further be analyzed across individual cancer types, target types, outcome and manufacturing conditions as examples. We anticipate this information will prove useful across many aspects of the development, manufacturing and clinical applications for cellular therapies and further hypothesize that these findings will promote the understanding of pathways affecting safety and efficacy that may help optimize the therapy.ConclusionsThe project is anticipated to begin Fall of 2021 with work continuing in phases through 2022 with periodic data reports to be shared through scientific conferences. All data and findings will be made publicly available to the scientific community through PICI’s Cancer Data and Evidence Library analysis platform (CANDEL).


2020 ◽  
Vol 22 (3) ◽  
pp. 286-305 ◽  
Author(s):  
Shuai Zhang ◽  
Brittany Bolduc Lachance ◽  
Bilal Moiz ◽  
Xiaofeng Jia

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.


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