Factors affecting the turnaround time for manufacturing, testing, and release of cellular therapy products prepared at multiple sites in support of multicenter cardiovascular regenerative medicine protocols: a Cardiovascular Cell Therapy Research Network

AbstractWith few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.

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Cell Therapy and Bioengineering in Experimental Liver Regenerative Medicine: In Vivo Injury Models and Grafting Strategies

Current Transplantation Reports ◽

10.1007/s40472-021-00325-2 ◽

2021 ◽

Author(s):

G. Amato ◽

T. Saleh ◽

G. Carpino ◽

E. Gaudio ◽

D. Alvaro ◽

...

Keyword(s):

Regenerative Medicine ◽

Cell Therapy ◽

Cell Delivery ◽

Effective Strategies ◽

Multiple Strategies ◽

End Stage ◽

Therapy Strategies ◽

Injury Models ◽

Experimental Liver

Abstract Purpose of Review To describe experimental liver injury models used in regenerative medicine, cell therapy strategies to repopulate damaged livers and the efficacy of liver bioengineering. Recent Findings Several animal models have been developed to study different liver conditions. Multiple strategies and modified protocols of cell delivery have been also reported. Furthermore, using bioengineered liver scaffolds has shown promising results that could help in generating a highly functional cell delivery system and/or a whole transplantable liver. Summary To optimize the most effective strategies for liver cell therapy, further studies are required to compare among the performed strategies in the literature and/or innovate a novel modifying technique to overcome the potential limitations. Coating of cells with polymers, decellularized scaffolds, or microbeads could be the most appropriate solution to improve cellular efficacy. Besides, overcoming the problems of liver bioengineering may offer a radical treatment for end-stage liver diseases.

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Benefits and obstacles to cell therapy in neonates: The INCuBAToR (Innovative Neonatal Cellular Therapy for Bronchopulmonary Dysplasia: Accelerating Translation of Research)

Stem Cells Translational Medicine ◽

10.1002/sctm.20-0508 ◽

2021 ◽

Author(s):

Bernard Thébaud ◽

Manoj Lalu ◽

Laurent Renesme ◽

Sasha Katwyk ◽

Justin Presseau ◽

...

Keyword(s):

Cell Therapy ◽

Bronchopulmonary Dysplasia ◽

Cellular Therapy

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Regenerative medicine and traumatic brain injury: from stem cell to cell-free therapeutic strategies

Regenerative Medicine ◽

10.2217/rme-2021-0069 ◽

2021 ◽

Author(s):

Lianxu Cui ◽

Yasmeen Saeed ◽

Haomin Li ◽

Jingli Yang

Keyword(s):

Traumatic Brain Injury ◽

Stem Cells ◽

Stem Cell ◽

Brain Injury ◽

Regenerative Medicine ◽

Cell Therapy ◽

Therapeutic Strategies ◽

Study Data ◽

Health Concern ◽

Standardized Treatment

Traumatic brain injury (TBI) is a serious health concern, yet there is a lack of standardized treatment to combat its long-lasting effects. The objective of the present study was to provide an overview of the limitation of conventional stem cell therapy in the treatment of TBI and to discuss the application of novel acellular therapies and their advanced strategies to enhance the efficacy of stem cells derived therapies in the light of published study data. Moreover, we also discussed the factor to optimize the therapeutic efficiency of stem cell-derived acellular therapy by overcoming the challenges for its clinical translation. Hence, we concluded that acellular therapy possesses the potential to bring a breakthrough in the field of regenerative medicine to treat TBI.

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Abstract 295: The Stem Cell Therapy to Prevent Expansion of Abdominal Aortic Aneurysm (STOP-AAA) Trial: Rationale and Design

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.295 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Michael P Murphy ◽

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Cell Therapy ◽

Autologous Bone Marrow ◽

Research Network ◽

Stem Cell Population ◽

Abdominal Aortic ◽

Autologous Bone

Background: Abdominal aortic aneurysm (AAA) is the 13 th leading cause of death in the United States. The only options for treatment at present for AAA are open surgical and endovascular repair, both of which are associated with significant morbidity, mortality, and expense.Thus AAA represents an unmet medical need. AAA pathogenesis is a multifactorial inflammatory process characterized by activation of T-cells,macrophages and neutrophils resulting in degradation of the aortic wall. Mesenchymal stromal cells (MSCs) suppress T-cell and macrophage activation, inhibit matrix metalloproteinases and have been shown to decrease aneurysm expansion in murine models. Methods: The STOP-AAA trial, from the NHLBI funded Cardiovascular Cell Therapy Research Network, is a randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of autologous bone marrow derived MSCs in suppressing expansion of small AAA (35-50mm).Forty patients will be randomized in a 1:1 fashion to receive systemic administration of placebo or 3 doses of 2x10 6 MSC/kg. at baseline, 24, and 52 weeks. The primary endpoint will be change in AAA diameter at 18 months as measured by a single blinded observer using contrast enhanced helical computed tomographic angiography (CTA).The secondary endpoints include time to elective repair, incidence of AAA related deaths and rupture,change in aortic mural inflammation at 18 months as quantified by F18-fluorodeoxyglucose (FDG) uptake with integrated positron emission tomography and computed tomography (PET/CT), changes in circulating mRNA, microRNA, and inflammatory cell profiles, changes in serum cytokine levels, and major adverse cardiac events. Conclusion: The STOP-AAA will be the first in man study to assess the efficacy of autologous bone marrow derived MSCs to suppress AAA expansion. Furthermore the data collected from this novel trial will provide unique mechanistic insights in the immunomodulatory properties of this stem cell population.

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The Iranian National Guideline for Cell Therapy and Regenerative Medicine

Regenerative Engineering and Translational Medicine ◽

10.1007/s40883-021-00239-6 ◽

2021 ◽

Author(s):

Javad Verdi ◽

Mahdi Shadnoush ◽

Ghasem Janbabai ◽

Alireza Shoae-Hassani ◽

Seyed Abdolreza Mortazavi-Tabatabei ◽

...

Keyword(s):

Regenerative Medicine ◽

Cell Therapy ◽

National Guideline

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Burden of illness for metastatic melanoma in Canada, 2011–2013

Current Oncology ◽

10.3747/co.23.3161 ◽

2016 ◽

Vol 23 (6) ◽

pp. 563 ◽

Cited By ~ 8

Author(s):

D.S. Ernst ◽

T. Petrella ◽

A.M. Joshua ◽

A. Hamou ◽

M. Thabane ◽

...

Keyword(s):

Metastatic Melanoma ◽

Burden Of Illness ◽

Registry Data ◽

Research Network ◽

Mutation Status ◽

Factors Affecting ◽

Time To Recurrence ◽

Disease Characteristics ◽

Initial Stage ◽

Sites Of Metastases

Background Detailed epidemiology for patients with advanced metastatic melanoma in Canada is not well characterized. We conducted an analysis of patients with this disease in the province of Ontario, with the aim being to study the presentation, disease characteristics and course, and treatment patterns for malignant melanoma.Methods In this Canadian observational prospective and retrospective study of patients with malignant melanoma, we used data collected in the Canadian Melanoma Research Network (cmrn) Patient Registry. We identified patients who were seen at 1 of 3 cancer treatment centres between April 2011 and 30 April 2013. Patient data from 2011 and 2012 were collected retrospectively using chart records and existing registry data. Starting January 2013, data were collected prospectively. Variables investigated included age, sex, initial stage, histology, mutation type, time to recurrence, sites of metastases, resectability, and previous therapies.Results A cohort of 810 patients with melanoma was identified from the cmrn registry. Mean age was 58.7 years, and most patients were men (60% vs. 40%). Factors affecting survival included unresectable or metastatic melanoma, initial stage at diagnosis, presence of brain metastasis, and BRAF mutation status. The proportion of surviving patients decreased with higher initial disease stages.Conclusions Using registry data, we were able to determine the detailed epidemiology of patients with melanoma in the Canadian province of Ontario, validating the comprehensive and detailed information that can be obtained from registry data.

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946 Standardized transcriptional profiling for optimizing cellular therapies: a multi-center PICI-NanoString collaboration

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.946 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A995-A995

Author(s):

Sarah Church ◽

Christina Bailey ◽

Sarah Warren ◽

Lisa Butterfield

Keyword(s):

Cell Therapy ◽

Cellular Therapy ◽

Expression Profiles ◽

Network Cell ◽

Cellular Therapies ◽

Cancer Data ◽

Individual Site ◽

Essential Components ◽

Study Gene Expression ◽

Car T

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).

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