Transplantation Society development of the science and clinical - PDF document

9/28/2016 Transplantation Society • development of the science and clinical practice Transplantation ‐ Building Bridges • scientific communication to Excellence • continuing education • guidance on the ethical practice How can we use our collective wisdom/education to optimize transplantation outcomes? Outline World Wide Transplantation • “State of the World” in transplantation • Current Limitations • Potential Solutions 1

9/28/2016 Global distribution of transplantation activity 2010 T r ansplantation r ate (pmp) <6 6 to <20 20 to <40 40 to <70 >70 T e rrito ry size is disto rte d in pro po rtio n to the numbe r o f o rgan transplants re po rte d fo r e ac h c o untry in 2010 Provided by Sarah White, George Institute Data source: Global Observatory on Donation and Transplantation (www.transplant-observatory.org), slide courtesy of S White 76,118 kidney tr 2.16 million Patients living on ansplants per for med in 2011 dialysis at 31st Dec ember 2011 On a waiting list for kidne y tr ansplantation in 2011 = 10,000 tr e ate d case s of kidne y failur e Provided by Sarah White Data sources: Global Observatory on Donation and Transplantation (www.transplant-observatory.org) ESRD Patients in 2011: A Global Perspective. Fresenius Medical Care. Bad Homburg, Germany. 2

9/28/2016 Current Issues in Transplantation Inadequate Numbers of Donors • Increasing numbers of recipients • Inadequate number of donor organs • Stagnant numbers of donors • Quality of donor organs • Long term complications of immunosuppression • Work force • Best practice Decreasing Demand ‐ Kidney Decreasing Demand ‐ Liver • HCV Rx • Weight loss ‐ dietary restriction • Bariatric surgery • Bariatric surgery • Treatment of fibrosis • Diabetic control • Lifestyle changes • Control hypertension • Compliance • Control rejection • Lifestyle changes • compliance • HCV treatment 3

9/28/2016 Quality of Donor Organs Mitigating Strategies • Fatty infiltration • Systemic Heparin • Older donors • High ‐ Dose Tissue Plasminogen Activator Flush • DCD • Aortic and portal vein flush • HCV+ donors • TPA prior to reperfusion • HIV+ donors • Fibrosis Mitigating Strategies • Machine preservation hypothermic vs. normothermic 4

9/28/2016 Prevention/treatment of Workforce Issues in Transplantation diseased organs • Develop network of transplant providers Heart • Historically multidisciplinary • cells • TTS partnership with ITNS • Mechanical support • Education Professional education Liver Guidelines • HCV Rx • Reversal of fibrosis • Reversal of fat infiltration Sister Centers Programs Minimum requirements to perform Linking Developing Centres deceased donor transplantation with established ones. Facilitating links developed by members Data Systems • To whom it may concern, Our hospital is located in Herat province of Afghanistan and We are a first ranked private 100 bed hospital in Afghanistan and the only Post Tx care HLA lab hospital that is doing the kidney transplantation surgeries inside the TTS has assisted country for the very first time. We have been able to successfully Organ Deceased donor Waiting list procurement transplant approx 20 patients since we started three months Myanmar & Fiji transplantation program ago. In these three months we have to come know that Partnership wth ISN for Renal Transplant Programs Develop Legislative the number of ESRD patients are much more than what we have Chronic On call team Drug program Framework for Organ expected at first,therefore, we are in need of your experiences and ICU Dialysis Minimum requirements support to accomplish this procedure smoothly. Program Donation & Transplantation Funding mechanisms Looking forward to hearing from you ASAP. Best Regards Legislative and Regulatory Framework ‐‐ Masoud Ghafoori Infrastructure/other specialist personnel Clinical care teams (surgeons, physicians and nursing) Legislation/regulation, financing and organization of health services delivery Source: J Chapman, Global Alliance for Transplantation meeting, Durban 2013 5

9/28/2016 ITN029ST Conclusions Withdrawal of Immunosuppression • Major goal of transplantation • Immunosuppression reduction / withdrawal with intense allograft monitoring has, thus far, been safe • Many different strategies • 12 / 20 participants are off of immunosuppression • Liver safer than kidney >1year with stable allograft function • Long term withdrawal after liver • 8 / 20 participants have failed withdrawal transplantation possible – 1 violation of inclusion / exclusion criteria • Best case – 5 for indeterminate ACR – Children – 2 for biopsy proven acute rejection – Living donor – Protocol biopsies over 5+ years do not show systematic – Further from transplant the better increase in either inflammation or fibrosis iWITH: Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients Building Organs 12 center, 100 patient prospective withdrawal trial • Define the prevalence of operational tolerance in • Clinical trials with stem cells are proceeding pediatric recipients of deceased and living donor liver transplants • Development of hepatocytes from patient’s • Determine safety of immunosuppression stem cells eliminates need for withdrawal immunosuppression • Derive biomarker of operational tolerance – Peripheral blood multi ‐ parameter flow cytometry – Peripheral blood and tissue microarray and QT ‐ PCR 6

9/28/2016 Post-Transplant Proliferation Hepatocytes Made from Skin Cells Reprogramming pluri- partial direct potency From Stem Cells to Liver Transplant • Organs need structure for long term function • Need to replace the original liver cells with recipient cells • Leave scaffold in place for function Po rcine liver decellularization. Whole native liver ( A ) before perfusion with Triton X ‐ 100 ( B ) and SDS ( C ). Indicated by panels on the SDS ‐ treated liver, the preserved major ( D ) and minor ( E ) vessels are visible at the end of the protocol American Journal of Pathology, Volume 183, Issue 2, 2013 7

9/28/2016 Building Organs • Infuse ghosts with hepatocytes. • Need endothelial cells, cholangiocytes, Kupffer cells? Novel Organs Ban lifted ‐ Human Stem cell work • EuroStemCell 2015 ‐ MRC Centre for Regenerative Medicine ‐ hepatic progenitors used to regrow damaged NIH to lift ban on funding research using livers in mice injected human stem cells into animals with • Cincinnati Children’s Hospital ‐ induced stem cells ‐ the specific purpose of try to grow human become human intestine and human stomach and tissues and organs in animals implanted in mouse • MRC (US) ‐ ghost kidney and ghost ‐ understand human diseases heart(UPitt)repopulated and functioned ‐ develop therapies for disease • Kings College and UCSF ‐ skin cells ‐ develop human organs for transplantation • Inst Mol Biotech(Austria and U Edinburgh) ‐ brain organoids 8

9/28/2016 Xeno ‐ transplant Pig Genome Modification • Pig organs may be ideal in terms of size and function • CRISPR/CAS 9 used to inactivate 62 PERVs in • Past use inhibited by presence of porcine pig embryos endogenous retro ‐ viruses (PERV) because of • Modification of 20 surface proteins thought concern of disease transmission. to be responsible for human immune • Surface proteins leading to rejection also response to pig cells. present Science. 2015 Oct 11. 9