A5073166198- Pancreatic function and diabetes
- Diabetes Management and Research
- Diabetes and associated disorders
- Pluripotent Stem Cells Research
- Genomics and Chromatin Dynamics
- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Chronic Myeloid Leukemia Treatments
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA Interference and Gene Delivery
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immunotherapy and Immune Responses
- Congenital heart defects research
- Histone Deacetylase Inhibitors Research
- S100 Proteins and Annexins
- Developmental Biology and Gene Regulation
- Bipolar Disorder and Treatment
- Xenotransplantation and immune response
- Reproductive tract infections research
- TGF-β signaling in diseases
- Preterm Birth and Chorioamnionitis
- Virus-based gene therapy research
- Infant Nutrition and Health
- Eosinophilic Disorders and Syndromes
ViaCyte (United States)
2012-2023
Center for Beta Cell Therapy in Diabetes
2020
General Atomics (United States)
2005-2013
Maastricht University
2012
National Cancer Institute
2004
Institute of Molecular and Cell Biology
2004
Japanese Foundation For Cancer Research
2004
Cancer Genetics (United States)
2004
Montreal Clinical Research Institute
1998-2003
Hôpital Maisonneuve-Rosemont
2002
Development of a human embryonic stem cell (hESC)-based therapy for type 1 diabetes will require the translation proof-of-principle concepts into scalable, controlled, and regulated manufacturing process. We have previously demonstrated that hESC can be directed to differentiate pancreatic progenitors mature functional glucose-responsive, insulin-secreting cells in vivo. In this study we describe expansion banking methods suspension-based differentiation system, which together underpin an...
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 releasing insulin a physiologically regulated fashion. In this of 17 subjects aged 22-57 with diabetes, PEC-01 were implanted subcutaneously VC-02 macroencapsulation devices, allowing for direct vascularization the cells. Engraftment and expression observed 63% units...
The PEC-01 cell population, differentiated from human embryonic stem cells (hESCs), contains pancreatic progenitors (PPs) that, when loaded into macroencapsulation devices (to produce the VC-01 candidate product) and transplanted mice, can mature glucose-responsive insulin-secreting other endocrine involved in glucose metabolism. We modified protocol for making such that 73%-80% of population consisted PDX1-positive (PDX1+) NKX6.1+ PPs. PPs were further to islet-like (ICs) reproducibly...
Clinical studies on the treatment of type 1 diabetes with device-encapsulated pancreatic precursor cells derived from human embryonic stem found that insulin output was insufficient for clinical benefit. We are conducting a phase 1/2, open-label, multicenter trial aimed at optimizing cell engraftment (ClinicalTrials.gov identifier: NCT03163511 ). Here we report interim, 1-year outcomes in one study group received 2-3-fold higher doses devices an optimized membrane perforation pattern. β...
Complex genetic and biochemical interactions between HOX proteins members of the TALE (i.e., PBX MEIS) family have been identified in embryonic development, some these also appear to be important for leukemic transformation. We previously shown that HOXA9 collaborates with MEIS1 induction acute myeloid leukemia (AML). In this report, we demonstrate HOXB3, which is highly divergent from HOXA9, genetically interacts MEIS1, but not PBX1, generating AML. addition, show HOXB3 genes play key roles...
VC-01 is a novel cell replacement therapy being developed as potential long-term diabetes to more effectively control glycemia, reduce hypoglycemia risk and mitigate diabetes-related complications. derived from directed differentiation of human embryonic stem cells pancreatic progenitor cells, which are loaded into durable, retrievable delivery device then implanted subcutaneously. Once matured, the secrete insulin other islet hormones in response blood glucose levels. The immunoprotective...
β-Cells generated from large-scale sources can overcome current shortages in clinical islet cell grafts provided that they adequately respond to metabolic variations. Pancreatic (non)endocrine cells develop human embryonic stem (huES) following vitro derivation pancreatic endoderm (PE) is subsequently implanted immune-incompetent mice for further differentiation. Encapsulation of PE increases the proportion endocrine subcutaneous implants, with enrichment β-cells when are placed...
Human stem cells represent a potential source for implants that replace the depleted functional beta cell mass (FBM) in diabetes patients. embryonic cell-derived pancreatic endoderm (hES-PE) can generate with glucose-responsive capable of reducing hyperglycemia mice. This study device-encapsulated hES-PE (4 × 106 cells/mouse) determines biologic characteristics at which establish metabolic control during 50-week follow-up. A metabolically adequate FBM was achieved by (1) formation sufficient...
To overcome the donor shortage in treatment of advanced type 1 diabetes by islet transplantation, human embryonic stem cells (hESCs) show great potential as an unlimited alternative source beta cells. hESCs may have immune privileged properties and it is important to determine whether these are preserved hESC-derived cells.We comprehensively investigated interactions both innate adaptive auto- allo-immunity with pancreatic progenitor endocrine cells, retrieved after in-vivo differentiation...
A recurrent translocation between chromosome 1 (Pbx1) and 19 (E2A) leading to the expression of E2A-Pbx1 fusion oncoprotein occurs in approximately 5 10% acute leukemias humans. It has been proposed that some oncogenic potential could be mediated through heterocomplex formation with Hox proteins, which are also involved human mouse leukemias. To directly test this possibility, bone marrow cells were engineered by retroviral gene transfer overexpress E2A-Pbx1a together Hoxa9. The results...
To understand the regulatory diversity of rat family linked kallikrein genes, we have assayed expression members in 20 major organs. Reverse transcription-polymerase chain reaction analysis using primers and hybridization probes specific for each 10 expressed genes showed that no two share same organ-specific pattern expression. The only common site all known active is submandibular gland. presence mRNA at least one member detected 19 these organs (liver excepted), from as few three to many...
Patients with T1D exhibit a major loss in beta cell mass, associated low or undetectable circulating markers of function. C-peptide serves as biomarker used to assess the residual mass functional insulin-producing pancreatic cells present patients on insulin replacement therapies; this measurement is not confounded by exogenous insulin. Novel therapies address T1D, including VC-02 (PEC-Direct), have demonstrated ability control disease state and mitigate diabetes-related complications due...