National Disease Research Interchange Advancing Medical Research Through Organ and Tissue Donation History & Overview NDRI Mission Statement To advance disease research through the procurement, preservation and distribution of human cells, tissues and organs. NDRI • Founded in 1980 • Based in Philadelphia • 501(c)(3) Governed by BOD • Operates 7 days a week, 24 hours a day • Served more than 5,000 investigators with over 300,000 biospecimens • Funded by the NIH for thirty-plus consecutive years • 2,700 publications Funded by National Institutes of Health for 30 Years NIH Office of the Director (ORIP, GTEx) NIDDK NEI NHGRI NIAMS NIAID ORDR NHLBI NIMH NCI Other Funding Streams Corporate • • Pharma/biotech industry Provided tissues to > 330 for-profit entities in last 5 years Special Initiatives • • • • • Cystic Fibrosis Foundation Collaboration Genotype-Tissue Expression Project ATSDR/Boston VA ALS Projects Joslin Medalist Diabetes Project Children’s Tumor Foundation Types of Tissue Requests Standard Requests • Eyes Custom Project Requests • Specialized sourcing • Solid organs • Special initiatives • Tissue bank specimens • Surgical specimens o o o o Eye sections Dorsal root ganglia GTEx ALS (VA, ATSDR) NDRI Reach & Network NDRI Procurement Network 240 Sites 56 Organ Procurement Organizations 46 Hospital Donor Sites 37 Eye Banks 23 Tissue Banks 18 Satellite Tissue Source Sites 200 Recovery Personnel Biospecimen Diversity • Normal • Diseased – common and rare • High quality, low-PMI organs and tissues • Brain/CNS • Cancer /normal adjacent • Cord blood/placenta/umbilical cord • Isolated normal /T1D/T2D pancreatic islet cells Versatility of Human Tissue in Research Viable, shipped at 4ºC • Stem cell isolation • • • • • • Regenerative medicine Cell culture Functional analysis Single cell analysis High throughput screening Toxicology/DMPK Snap-frozen/fixed • Expression analysis • Genotyping • IHC • Proteomics • Biomarkers • Biomechanics Functional Analysis Project Examples Genotype Tissue Expression Project (GTEX) • 5 year project - August 2010 to 2015 • 400 post mortem donors consented and recovered – 69% authorization rate • PMI range 1:22 to 6:51 (O), 7:01 to 24:00 (T) • 44,341 biospecimens collected • 96% released to NIH CaHuB inventory • 84% RNA integrity number > 6 GTEx Post-mortem Organs and Tissues • Skeletal muscle • Tibial nerve • Tibial artery • Skin (leg) • Adipose tissue • Whole brain • Brain tissues (cerebellum and cortex) • Heart (left anterior ventricle, right atrial appendage, coronary artery and aorta) • Greater omentum • Mammary tissue (male and female) • Lung • Stomach • Esophagus (mucosa and muscularis propria) • Pituitary gland • Thyroid gland • Minor salivary gland • • Skin (suprapubic region) Gastroesophageal junction • Liver • Spleen • Pancreas • Colon (transverse and sigmoid) • Lymphoid tissue of terminal ileum • Kidney (cortex) • Adrenal glands • Female (uterus, ovary and vagina) • Male (prostate gland and testes) GTEx Biospecimen Source Site Comparisons Heart Line : Y = -0.18295*X + 8.31891 Pearson correlation: r = -0.639804 t-score = -7.675229 Colon Line : Y = -0.18796*X + 7.89886 Pearson correlation: r = -0.722165 t-score = -10.543999 Cystic Fibrosis • Explanted lungs recovered from CF patients undergoing transplant • NDRI provided ~200 CF lungs for Cystic Fibrosis Foundation-funded project • Two new drugs developed Type 1 Diabetes • Pancreas, kidney, eyes recovered from long-standing T1D patients • Nationwide recoveries using NDRI Private Donor Program Amyotrophic Lateral Sclerosis • Two projects funded by • ATSDR/McKing Corp – 30 patients targeted for recovery • Boston VA – 200 patients registered • Patients identified and consented by collaborators • Nationwide recoveries using NDRI Private Donor Program o Collects brain, spinal cord, CSF, bone & skin o Recoveries completed < 24 hours post mortem NDRI Research Services Biospecimen Application Process • Application – – – – Tissue needs/donor profile IRB documentation Project synopsis CV/biosketch • Feasibility review – internal/external • Customized protocol development Standard Authorization/Consent • Protocol approved by Univ. of Pennsylvania IRB • Risk mitigation a priority • Authorization for general research including o For profit o Therapeutics and diagnostics o Genome sequencing • Potential access to complete health record • No payment to donor or family decision maker Customized Authorization/Consent • Project specific IRB approval • Incorporates additional objectives (e.g. product development) • Right to withdraw limits • Addresses risks associated with loss of identity (genotyping) • Unknown future uses • Cell line development (unlimited future use) Summary • Project-driven services to scientists • Nationwide collection centers • Worldwide distribution capabilities • Diseased and normal biospecimens available from multiple donor types • SOPs and total QMS in place for consent, recovery, & distribution Acknowledgements