Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Concise Review: Manufacturing of Pancreatic Endoderm Cells for Clinical Trials in Type 1 Diabetes.

ABSTRACT: The cellular component of ViaCyte's VC-01 combination product for type 1 diabetes, pancreatic endoderm cells (PEC-01) derived from CyT49 human embryonic stem cells, matures after transplantation and functions to regulate blood glucose in rodent models. The aims in manufacturing PEC-01 at scale are to generate a consistent and robust transplantable population that functions reliably and safely in vivo. ViaCyte has integrated multiple bioprocessing strategies to enable a tightly controlled PEC-01 manufacturing process for clinical entry.

SUBMITTER: Schulz TC

PROVIDER: S-EPMC4511151 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Concise Review: Manufacturing of Pancreatic Endoderm Cells for Clinical Trials in Type 1 Diabetes.

Schulz Thomas C TC

Stem cells translational medicine 20150610 8

The cellular component of ViaCyte's VC-01 combination product for type 1 diabetes, pancreatic endoderm cells (PEC-01) derived from CyT49 human embryonic stem cells, matures after transplantation and functions to regulate blood glucose in rodent models. The aims in manufacturing PEC-01 at scale are to generate a consistent and robust transplantable population that functions reliably and safely in vivo. ViaCyte has integrated multiple bioprocessing strategies to enable a tightly controlled PEC-01 ...[more]

PMID: 26062982

Similar Datasets

Concise Review: Lessons Learned from Islet Transplant Clinical Trials in Developing Stem Cell Therapies for Type 1 Diabetes.

Project description:We examined data and patterns in clinical islet transplant studies registered on ClinicalTrials.gov (CTgov) for treatment of type 1 diabetes (T1D), with a goal of extracting insights to apply in the design of a pluripotent stem cell-derived islet therapy. Clinical islet transplantation, as a cell therapy (rather than solid organ transplant) is a unique precedent for stem cell-based islet therapies. Registration activity shows that the field is not growing significantly, and newer registrations suggest that the reasons for stagnation include need for a more optimal site of infusion/transplantation, and especially a need for better immune protective strategies to advance a more effective and durable therapy for T1D. Stem Cells Translational Medicine 2019;8:209&214.

| S-EPMC6392394 | biostudies-literature

Manufacturing mesenchymal stromal cells for phase I clinical trials.

Project description:Mesenchymal stromal cells (MSCs) are multipotent progenitor cells capable of differentiating into adipocytes, osteoblasts and chondroblasts as well as secreting a vast array of soluble mediators. This potentially makes MSCs important mediators of a variety of therapeutic applications. They are actively under evaluation for immunomodulatory purposes such as graft-versus-host disease and Crohn's disease as well as regenerative applications such as stroke and congestive heart failure. We report our method of generating clinical-grade MSCs together with suggestions gathered from manufacturing experience in our Good Manufacturing Practices facility.

| S-EPMC3611961 | biostudies-literature

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells.

Project description:Pancreatic adenocarcinoma remains one of the most challenging diseases of modern gastroenterology, and, even though considerable effort has been put into understanding its pathogenesis, the exact molecular mechanisms underlying the development and/or systemic progression of this malignancy still remain unclear. Recently, much attention has been paid to the potential role of bone marrow-derived stem cells (BMSCs) in this malignancy. Hence, herein, we comprehensively review the most recent discoveries and current achievements and concepts in this field. Specifically, we discuss the significance of identifying pancreatic cancer stem cells and novel therapeutic approaches involving molecular interference of their metabolism. We also describe advances in the current understanding of the biochemical and molecular mechanisms responsible for BMSC mobilization during pancreatic cancer development and systemic spread. Finally, we summarize experimental, translational, and/or clinical evidence regarding the contribution of bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem/progenitor cells, and pancreatic stellate cells in pancreatic cancer development/progression. We also present their potential therapeutic value for the treatment of this deadly malignancy in humans.Different bone marrow-derived stem cell populations contribute to the development and/or progression of pancreatic cancer, and they might also be a promising "weapon" that can be used for anticancer treatments in humans. Even though the exact role of these stem cells in pancreatic cancer development and/or progression in humans still remains unclear, this concept continues to drive a completely novel scientific avenue in pancreatic cancer research and gives rise to innovative ideas regarding novel therapeutic modalities that can be safely offered to patients.

| S-EPMC4922853 | biostudies-other

Clinical trials in youth with type 2 diabetes.

Project description:Type 2 diabetes in youth was almost unheard of only two decades ago. However, tracking the recent dramatic rise in childhood obesity, type 2 diabetes has become increasingly prevalent. Thus, there is an urgent need for high-quality clinical trials to increase in-depth knowledge about pathophysiology, optimal treatment, and prevention. We therefore systematically reviewed published and ongoing clinical trials of type 2 diabetes in children and adolescents. The results demonstrate that (i) few randomized clinical trials have been completed and published in children with type 2 diabetes; (ii) ongoing trials in type 1 diabetes clearly outnumber trials in type 2 diabetes; and (iii) recruitment and enrollment into the latter trials are challenging, however once achieved, drop-out rates are not excessively high. We conclude that type 2 diabetes in youth is an important but difficult new field of clinical research, and we discuss the existing barriers to successful recruitment, conduct, and support of these clinical trials.

| S-EPMC3405735 | biostudies-other

Linagliptin for type 2 diabetes mellitus: a review of the pivotal clinical trials.

Project description:Patients with type 2 diabetes mellitus (T2DM) frequently require multiple therapies to effectively control hyperglycemia, and many new agents for glucose control have been developed over the past few decades. Linagliptin is a recently approved oral antidiabetic drug that acts by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4). Unlike other DPP-4 inhibitors, linagliptin is excreted chiefly via the enterohepatic system, and can be used without dose adjustment in patients with renal or hepatic impairment. Linagliptin was approved by the US Food and Drug Administration based on a large development program, including four pivotal trials in patients with T2DM, assessing the efficacy and safety of linagliptin when used as monotherapy or in combination with other oral antidiabetes drugs. Linagliptin was associated with significant improvements in glycosylated hemoglobin, fasting plasma glucose and postprandial glucose, and more patients receiving linagliptin showed meaningful improvements and achieved targets for glycosylated hemoglobin. Linagliptin was well tolerated, with an adverse event profile similar to that of placebo, and low rates of hypoglycemic events. Taken together, the pivotal trials confirm linagliptin is effective and safe in patients with T2DM: the convenience of oral dosing with no requirement for dose adjustment in patients with renal or hepatic impairment make linagliptin a valuable option when considering therapies for patients with T2DM.

| S-EPMC3498850 | biostudies-literature

Transplantation of Human Pancreatic Endoderm Cells Reverses Diabetes Post Transplantation in a Prevascularized Subcutaneous Site.

Project description:Beta-cell replacement therapy is an effective means to restore glucose homeostasis in select humans with autoimmune diabetes. The scarcity of "healthy" human donor pancreata restricts the broader application of this effective curative therapy. "?-Like" cells derived from human embryonic stem cells (hESC), with the capacity to secrete insulin in a glucose-regulated manner, have been developed in vitro, with limitless capacity for expansion. Here we report long-term diabetes correction in mice transplanted with hESC-derived pancreatic endoderm cells (PECs) in a prevascularized subcutaneous site. This advancement mitigates chronic foreign-body response, utilizes a device- and growth factor-free approach, facilitates in vivo differentiation of PECs into glucose-responsive insulin-producing cells, and reliably restores glycemic control. Basal and stimulated human C-peptide secretion was detected throughout the study, which was abolished upon graft removal. Recipient mice demonstrated physiological clearance of glucose in response to metabolic challenge and safely retrieved grafts contained viable glucose regulatory cells.

| S-EPMC5470173 | biostudies-literature

Strategies for clinical trials in type 1 diabetes.

Project description:During the past one to two decades, substantial progress has been made in our understanding of the immunopathology of type 1 diabetes (T1D) and the potential for immune interventions that can alter the natural history of the disease. This progress has resulted from the use of standardized study designs, endpoints, and, to a certain extent, mechanistic analyses in intervention trials in the setting of new-onset T1D. To date, most of these trials have involved single-agent interventions but, increasingly, future trials will test therapeutic combinations that are based on a compelling scientific rationale and testable mechanistic hypotheses. These increasingly complex trials will benefit from novel trial designs (such as factorial or adaptive designs), enhanced clinical endpoints that more directly assess islet pathology (such as ?-cell death assays and islet or pancreatic imaging), improved responder analyses, and sophisticated mechanistic assays that provide deep phenotyping of lymphocyte subsets, gene expression profiling, in vitro T cell functional assessments, and antigen-specific responses. With this developing armamentarium of enhanced trial designs, endpoints, and clinical and mechanistic response analyses, we can expect substantial progress in better understanding the breakdown in immunologic tolerance in T1D and how to restore it to achieve significant and long-lasting preservation of islet function.

| S-EPMC4903883 | biostudies-literature

Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device.

Project description:These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion. In this study of 17 subjects aged 22-57 with type 1 diabetes, PEC-01 cells were implanted subcutaneously in VC-02 macroencapsulation devices, allowing for direct vascularization of the cells. Engraftment and insulin expression were observed in 63% of VC-02 units explanted from subjects at 3-12 months post-implant. Six of 17 subjects (35.3%) demonstrated positive C-peptide as early as 6 months post-implant. Most reported adverse events were related to surgical implant or explant procedures (27.9%) or to side-effects of immunosuppression (33.7%). Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants.

| S-EPMC8714853 | biostudies-literature

Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes.

Project description:The evolution of Type 1 diabetes (T1D) therapy has been marked by consecutive shifts, from insulin replacement to immunosuppressive drugs and targeted biologics (following the understanding that T1D is an autoimmune disease), and to more disease-specific or patient-oriented approaches such as antigen-specific and cell-based therapies, with a goal to provide efficacy, safety, and long-term protection. At the same time, another important paradigm shift from treatment of new onset T1D patients to prevention in high-risk individuals has taken place, based on the hypothesis that therapeutic approaches deemed sufficiently safe may show better efficacy if applied early enough to maintain endogenous β cell function, a concept supported by many preclinical studies. This new strategy has been made possible by capitalizing on a variety of biomarkers that can more reliably estimate the risk and rate of progression of the disease. More advanced ("omic"-based) biomarkers that also shed light on the underlying contributors of disease for each individual will be helpful to guide the choice of the most appropriate therapies, or combinations thereof. In this review, we present current efforts to stratify patients according to biomarkers and current alternatives to conventional drug-based therapies for T1D, with a special emphasis on cell-based therapies, their status in the clinic and potential for treatment and/or prevention.

| S-EPMC5021120 | biostudies-literature

A review of clinical trials: mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus.

Project description:Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass. Both diseases can cause severe health consequences. Despite the globally increasing prevalence of both T1DM and T2DM there remains to be a medically defined cure for either of these diseases. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible curative treatment method. In this review, we explain the molecular mechanisms underlying MSCs and their potential ability to treat T1DM and T2DM. We describe the capability of MSCs to differentiate into insulin-producing cells and regenerate pancreatic beta cells, as well as assess their role in modulating the immune system. Lastly, we evaluate the current literature focusing on the clinical application of MSC transplantation in T1DM and T2DM. Despite the favorable results, study designs and analyses cast doubt on the effectiveness of MSCs for the management of T1DM. Conversely, the positive metabolic effects consistently demonstrated in the literature offer hope for MSCs as a treatment for T2DM, at least in the short-term.

| S-EPMC6261870 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data