The Future of Transplantation
Atul Humar, MD
2017 CST-Astellas Canadian Transplant Fellows Symposium
Atul Humar is a Professor in the Department of Medicine, University ofToronto. Dr. Humar received his medical degree from the University ofOttawa. He completed his residency and did further training inTransplant Infectious Diseases in Toronto and Boston. Dr. Humar’sresearch interests are in virology with a focus on the pathogenesis ofherpesvirus infections post-transplant. He is involved in both basic andclinical research assessing immunologic and virologic determinants ofinfection. Dr. Humar is the Director of Multi Organ Transplant Programat the University Health Network and the University of TorontoTransplant Institute. He is also active in the Canadian Society ofTransplantation as a President and has been very active in both theAST and TTS. Dr. Humar operates a joint research lab with his wife, Dr.Deepali Kumar, who is also a faculty member at the University ofToronto.
The Future of Transplantation
Atul Humar, MD
Herrick twins 1954
1960
Year of transplant
Ac
ute
re
jec
tio
n/g
raft
su
rviv
al
(%)
80–90%
40–50%
5–20%
~60%
Azathioprine
PrednisoneCsA
MMF
Basiliximab
Tacrolimus
Sirolimus
Acute rejection80
100
60
20
40
2005 1965 1970 1975 1980 1985 1990 1995 2000 2010
0
ATG
Amazing AccomplishmentsWho would have believed it?…
1-year
graft survival
Everolimus
CsA, ciclosporin; ATG, anti-thymocyte globulin; MMF, mycophenolate mofetil
1. Morris PJ. N Engl J Med. 2004;351:267880; 2. Sayegh MH, et al. N Engl J Med. 2004;351:27616;
3. Khurana A, Brennan D. Current concepts of immunosuppression and side effects in Pathology of Solid Organ Transplantation, 2011 6
Benchmarking: One year Graft Survival Rate
0
20
40
60
80
100
Kidney
DD
Kidney
LD
Liver
DD
Liver
LD
Lung Heart Pancreas
1 year (%) UHN 1 year (%) US/International
One Year Transplant Survival comparison to available benchmark
Data source: OTTR, UNOS (SRTR) and ISHLT
Benchmarking: Ten year Graft Survival Rate
0
20
40
60
80
100
Kidney
DD
Kidney
LD
Liver
DD
Liver
LD
Lung Heart Pancreas
10 year (%) UHN 10 year (%) US/International
Ten Year Transplant Survival comparison to available benchmark
Data source: OTTR, UNOS (SRTR) and ISHLT 2004-13
Transplant Waiting List
Will the waiting list go down with new treatments for disease?
The FUTURE OF TRANSPLANTATION
Solving organ failure
Organ Utilization
Organ Donation
New sources / technologies
Regenerative medicine / bioengineering
Lung
Heart
Kidney
Liver
Organ Repair Lab
Ray Owen
The Holy Grail..Immune Tolerance
Regenerative medicine: Cellular Transplantation, stem cells, bioengineering
www.sernova.com
Islet
Transplan
t
Scheme of beta cell development
Human
pluripotent
stem
Definitive
endoderm
Pancreatic progenitors
insulin+glucagon+
NKX6.1-
first transition population
'primitive cells'
insulin+glucagon-
NKX6.1+
PDX-1+NKX6.1+
PDX-1+?NKX6.1-
CD142-
glucagon+
alpha cells
+additional
factors
2nd Transition
INS GCG DAPI INS SST DAPI
Islet structures derived from human ESCs
Nature Medicine 2010 Aug 16 (8): 927-33.
Decellularize: perfusion with detergents and phosphate buffered salineRecellularize: epithelial and endothelial cell seeding followed by transplantation
STEM CELLS, REGENERATIVE MEDICINE, BIOENGINEERING
Growing Organs in the Lab
Ott, H. Nature Medicine, 2010 Ott, H. Nature Medicine, 2008
BLASTOCYST COMPLEMENTATION: INTERSPECIES
ORGANOGENESIS
What is CRISPR?
• Genome-editing tool originally
discovered in prokaryotes
• Consist of specialized guide RNAs
(crRNAs) that are linked to a nuclease
(cas9)
• crRNAs are complimentary to target
regions of the genome
• If annealing takes place, nuclease causes
double stranded breaks in DNA
• Gene inactivation
(A) Image of the first born PERV-inactivated pig (B) PERV inactivation at genomic DNA level
Transplantation-The Future
• First 50 years of Transplantation (1960-2010)
– Solid organ transplantation (SOT) is now recognized as a highly effective therapy for patients with end stage organ injury.
• The next 50 years in Transplantation
– Opportunities to solve organ donor shortage
– Tolerance is achievable..at least in some
– New Technologies offer unparalleled opportunities… specifically the Regenerative Medicine field is poised to revolutionize all aspects of medicine
– Research Funding is now improving both for basic and translational research programs
27
Thanks you!
Questions?
28
http://hqgrandeprairie.com/health/human-head-
transplant-crazy-gamble/024939
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