Transplantation Society. Transplantation Building Bridges to Excellence. World Wide Transplantation. Outline 9/28/2016

Transcription

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

2 Global distribution of transplantation activity 2010 Transplantation rate (pmp) <6 6 to <20 20 to <40 40 to <70 >70 Territory size is distorted in proportion to the number of organ transplants reported for each country in 2010 Provided by Sarah White, George Institute Data source: Global Observatory on Donation and Transplantation ( slide courtesy of S White 76,118 kidney transplants performed in 2011 On a waiting list for kidney transplantation in million Patients living on dialysis at 31st December 2011 Data sources: Global Observatory on Donation and Transplantation ( ESRD Patients in 2011: A Global Perspective. Fresenius Medical Care. Bad Homburg, Germany. = 10,000 treated cases of kidney failure Provided by Sarah White 2

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

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

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

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

7 Hepatocytes Made from Skin Cells Post-Transplant Proliferation Reprogramming pluripotency partial direct 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 Porcine 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,

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

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