Insulin producing cells from amniotic stem cells for diabetes therapy

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Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
Project Description:
[unreadable] (provided by applicant): Diabetes mellitus is a growing problem worldwide. In the US it affects over 18 million people and results in annual health care costs exceeding $130 billion. Insulin therapy of Type 1 diabetes, and in advanced cases of Type 2 diabetes, does not prevent serious long-term complications including neuropathy, vascular disease, retinopathy and renal failure. Transplantation of pancreatic islets to restore insulin production offers significant promise. However, the supply of donor pancreata falls far short of meeting the medical need. New sources of insulin producing cells will be required to realize the full potential of cell therapy for diabetes. We propose to generate pancreatic beta lineage cells by in vitro differentiation of stem cells isolated from amniotic fluid. These "AFS cells" are capable of both extensive expansion and differentiation into derivatives of all three embryonic germ layers. Our Preliminary Studies showed that mouse AFS cells can yield insulin producing cells and islet-like cell clusters ("neo-islets"), promoted by expression of the pancreatic transcription factor PDX-1. We now propose to produce neo-islets from human and non-human primate (NHP) AFS cells. To efficiently generate insulin producing cells, we will optimize delivery of a plasmid vector to express PDX-1, and will systematically test growth factors and substrates shown previously to promote pancreatic beta cell differentiation. The resulting neo-islets will be compared with authentic human and NHP pancreatic islets using tests developed for clinical transplantation. To assess their ability to restore control of glucose metabolism and production of insulin and C-peptide, neo-islets will be implanted in immunodeficient mice made diabetic with streptozotocin (STZ). Transplantation in STZ-treated NHP will assess the function of neo-islets in a model physiologically more similar to humans. NHP AFS cell lines will be derived after amniocentesis of pregnant mothers. These stem cells will be used to generate neo-islets for autologous transplantation into the corresponding offspring. The same donor cells will be compared in allogeneic recipients using clinically relevant immunosuppression regimens. Successful development of an abundant source of transplantable insulin producing cells potentially would have a profound impact on the treatment of a major public health problem. [unreadable] [unreadable] [unreadable]
 
Project Terms:
2-Deoxy-2-((methylnitrosoamino)carbonyl)amino-D-glucose 2-deoxy-2-(3-methyl-3-nitrosoureido)-D-glucopyranose 2-deoxy-2-[[(methylnitrosamino)-carbonyl]amino]-D-glucopyranose Address Affect Allogenic Amniocentesis Amniotic Fluid Aqua Amnii Autograft Autologous Autologous Transplantation Autotransplant B9 endocrine pancreas Beta Cell C-Peptide Cell Differentiation Cell Differentiation process Cell Line Cell Lineage Cell Lines, Strains Cell Therapy Cell Transplantation CellLine Cells Chemotherapy-Hormones/Steroids Clinical Clonal Expansion Connecting Peptide Development Diabetes Mellitus Diabetes Mellitus, Adult-Onset Diabetes Mellitus, Brittle Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus, Juvenile-Onset Diabetes Mellitus, Ketosis-Prone Diabetes Mellitus, Ketosis-Resistant Diabetes Mellitus, Non-Insulin-Dependent Diabetes Mellitus, Noninsulin Dependent Diabetes Mellitus, Slow-Onset Diabetes Mellitus, Stable Diabetes Mellitus, Sudden-Onset Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Type I Diabetes Mellitus, Type II Disease Disorder Donor, Organ Drugs Embryo Embryonic Endocrine Gland Secretion Face GFAC Gastrointestinal Tract, Pancreas Genes, Regulator Germ Layers Goals Grafting, Islets of Langerhans Growth Agents Growth Factor Growth Factors, Proteins Growth Substances Health Care Costs Health Costs Healthcare Costs Hormones Human Human, General Humulin R IDD IDDM Immunodeficient Mouse Immunosuppressants Immunosuppression Effect Immunosuppressions (Physiology) Immunosuppressive Agents Immunosuppressive Effect Implant In Vitro Insulin Insulin (ox), 8A-L-threonine-10A-L-isoleucine-30B-L-threonine- Insulin Cell Insulin Secreting Cell Insulin, Regular Insulin-Dependent Diabetes Mellitus Islands of Langerhans Islet Cell Islet Cells Islets of Langerhans Islets of Langerhans Transplantation Kidney Failure Kidney Insufficiency Laboratories Liquor Amnii MODY Mammals, Mice Man (Taxonomy) Man, Modern Maturity-Onset Diabetes Mellitus Medical Medication Mice Modeling Mother Cells Mothers Murine Mus NIDDM Natural immunosuppression Nesidioblasts Neuropathy Non-Insulin Dependent Diabetes Non-Insulin-Dependent Diabetes Mellitus Novolin R Organ Donor Pancreas Pancreas, Endocrine Pancreatic Pancreatic Islets Pancreatic beta Cell Pars endocrina pancreatis Patients Pharmaceutic Preparations Pharmaceutical Preparations Phase Phenotype Plasmid Cloning Vector Plasmid Vector Pluripotent Stem Cells Population Production Progenitor Cells Program Development Programs (PT) Programs [Publication Type] Protocols, Treatment Public Health RGM Regimen Regulator Genes Renal Failure Renal Insufficiency Research Retinal Diseases Retinal Disorder STZ Source Stem cells Streptozocin Streptozotocin Structure of beta Cell of islet System System, LOINC Axis 4 T1 diabetes T1D T1DM T2D T2DM Testing Therapeutic Hormone Therapy, Cell Transcriptional Regulatory Elements Transplantation Transplantation, Autologous Transplantation, Islands of Langerhans Transplantation, Islands of Pancreas Transplantation, Islet Transplantation, Pancreatic Islets Treatment Protocols Treatment Regimen Treatment Schedule Type 1 diabetes Type 2 diabetes Type II diabetes Vascular Diseases Vascular Disorder Waters (Amniotic Fluid) Zanosar adult onset diabetes amniotic fluid derived stem cell amniotic fluid stem cell base beta cell development blood glucose regulation blood vessel disorder cell type cell-based therapy clinical relevance clinically relevant cultured cell line diabetes diabetes mellitus therapy diabetes therapy diabetic disease/disorder drug/agent endocrine pancreas endocrine pancreas development experiment experimental research experimental study facial falls glucose control glucose homeostasis glucose metabolism glucose regulation hESC human ES cell human ESC human embryonic stem cell immunosuppression immunosuppressive improved in vivo insulin dependent diabetes insulin secretion islet islet beta cell transplantation islet cell transplant islet cell transplantation islet development islet progenitor islet transplantation juvenile diabetes juvenile diabetes mellitus ketosis prone diabetes ketosis resistant diabetes maturity onset diabetes meetings neuropathic non-human primate nonhuman primate novel offspring pancreas beta cell patient population pre-clinical preclinical pregnant prevent preventing progenitor programs public health medicine (field) quantum regulatory gene research study retina disease retina disorder retinopathy stem stem cell differentiation trans acting element transcription factor transplant type I diabetes vector
Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
Project Categories:
• Natural Sciences > Aging Diseases and Pathology > Cancer & related diseases > Malignant neoplasms (including in situ) > Gastrointestinal cancers > Pancreatic Cancer
 
Other Information:
Fiscal Year: 2007
Project Start Date: 30 September 2007
Project End Date: 31 August 2011
Administering Institute Or Center: EB
 
Project Funding Information:
Total Funding: $1,025,080
Year Funding Organization Total Funding, $
2009 NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING $1,025,080
Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
Project_number Title Year FY Total Cost
There are no results for this project in database.
Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
Project number Project title Organization FY Funding Organization FY Total Cost
1R01EB008009-01Insulin Producing Cells from Amniotic Stem Cells for Diabetes TherapyWAKE FOREST UNIVERSITY HEALTH SCIENCES2007NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
$1,058,000
5R01EB008009-02Insulin Producing Cells from Amniotic Stem Cells for Diabetes TherapyWAKE FOREST UNIVERSITY HEALTH SCIENCES2008NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
$1,025,080
3R01EB008009-01S1Insulin Producing Cells from Amniotic Stem Cells for Diabetes TherapyWAKE FOREST UNIVERSITY HEALTH SCIENCES2008NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
$111,000
3R01EB008009-02S1Insulin Producing Cells from Amniotic Stem Cells for Diabetes TherapyWAKE FOREST UNIVERSITY HEALTH SCIENCES2009NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
$38,766
5R01EB008009-03Insulin Producing Cells from Amniotic Stem Cells for Diabetes TherapyWAKE FOREST UNIVERSITY HEALTH SCIENCES2009NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING
$1,025,080
Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
Project number Project title Principal investigator
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Project Title: Insulin producing cells from amniotic stem cells for diabetes therapy
Principal Investigators (PI): ATALA ANTHONY
Project Number: 5R01EB008009-03
Organization: WAKE FOREST UNIVERSITY HEALTH SCIENCES
 
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