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?

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http://hqgrandeprairie.com/health/human-head-

transplant-crazy-gamble/024939