Kim Solez combining resources in tx and regen med make no small plans TERMIS-AM Meeting Dec. 4 2019

1. Combining Resources in
Transplantation and Regenerative
Medicine:
Kim Solez, MD
2019 TERMIS-AM Meeting
Make No Small Plans

2. Regenerative
Medicine
Organ
Regeneration
Organ Repair
Whole Organ
Manufacturing
Regenerative medicine (RM) is a field in the health sciences that aims to
regenerate, repair or replace functionally impaired tissues and organs in
order to restore function. - Giuseppe Orlando, M.D., Ph.D.
The process of regenerating body parts can occur in vivo or ex vivo and
may require cells, natural or artificial scaffolding materials, growth
factors, genetic manipulation, or combinations of them.
RM promises to address the longest standing limitations of organ
transplantation:
1 – the identification of an inexhaustible source of transplantable organs
2 – immunosuppression (IS)-free transplantation
3 – organs-on-demand.
This will rule out the need for lifelong IS and ischemia-reperfusion, by
allowing implantation of the graft immediately RM will eliminate the
waiting list..

3. PHASES IN THE HISTORY OF ORGAN TX
1900 1970 2000
Surgery
Organ preservation
Tissue typing
I/R
Xenotransplantation
Immunosuppression
Tolerance
Expansion of indications
Expansion of donor pool
Expansion of type of
transplants
Omics technology
Xenotransplantation
Big Data
Organ Bioengineering,
Regeneration & Repair
- Identification of a new,
inexhaustible source of organs
- IS-free transplantation
- Full Way Technology
- Organ on demand
CRISPR-Xenotransplantation
Big Data
Incentives to Donation
Omics technology
SURGERY IMMUNOLOGY REGENERATIVE
MEDICINE

4. BANFF CLASSIFICATION TRANSPLANT
PATHOLOGY MEETINGS SINCE 1991
FOUNDED BY SOLEZ/ RACUSEN

5. BANFF CLASSIFICATION TRANSPLANT
PATHOLOGY MEETINGS SINCE 1991
CONSENSUS GENERATION TECH

6. TRANSPLANT PATHOLOGISTS BECOME
TISSUE ENGINEERING PATHOLOGISTS -
PLAYS OUT IN BANFF IN EVERY ORGAN
• As identified in 2017 Banff meeting in Barcelona, it is our
intention that every organ system in the Banff Meetings and
Consensus Process will be engaged in planning their
regenerative medicine future. New Banff Classification of
Tissue Engineering Pathology. (AJT Personal Viewpoint 2018)
• That may be easier for our newest partners GI pathologists
where they look at stem cells in crypts every day and the
epithelium renews every 4-5 days. In other organs the activities
of stem cells are much more nuanced!

7. TRANSPLANT PATHOLOGISTS BECOME
TISSUE ENGINEERING PATHOLOGISTS -
PLAYS OUT IN BANFF IN EVERY ORGAN
• Stem cells in the
intestinal epithelium.

8. TRANSPLANT PATHOLOGISTS
BECOME TISSUE ENGINEERING
REGEN. MEDICINE PATHOLOGISTS
• First Suggested in After Dinner Speech at Banff 2011 in Paris
• The Canadian Society of Transplantation met jointly with the Cell Therapy
Regenerative Medicine Society in Halifax in 2017
• The Canadian Transplant Summit since 2018 includes Regenerative Medicine
• Tx Regen Med COP of AST (Giuseppe Orlando - Kim Solez) Planning First World
Congress on Regenerative and Transplant Medicine (FWCRTM) involving AST,
ASTS, ESOT, TXAST, TTS, IPITA, IXS, ISVCA, CTRMS, TERMIS, ISCT, and ISSCR in
Boston in April 2021. Currently in discussion with these organizations.
At this FWCRTM meeting Regen Med and Transplant communities would be discussing
together their common future. Currently identifying who will be lead organization(s). Smaller
organizations have already signed on. All conversations positive so far.
Also Tx - Regen Med cooperation a major theme of 2021 Banff meeting Oct. 4-7 at Banff
Centre which will be live streamed. Our 2021 meeting will sustain momentum of FWCRTM.

9. FIRST WORLD CONGRESS OF
REGENERATIVE AND TX MED
TIMELINE ROADMAP

10. FIRST WORLD CONGRESS OF
REGENERATIVE AND TX MED
COMBINING RESOURCES
AT LEAST 6 ORGANIZATIONS
WORKING TOGETHER WITH ONE IN
LEAD

11. FIRST WORLD CONGRESS OF
REGENERATIVE AND TX MED
IMPORTANT TAIL NOT WAG DOG

12. THE FUTURE AND ALL THAT JAZZ
REGEN MED IN POETRY AND MUSIC

13. THE FUTURE AND ALL THAT JAZZ
PERFORMED AT TERMIS-AM IN 2017

14. THE FUTURE AND ALL THAT JAZZ
MALLORY CHIPMAN BAND HAS ADDED
MOD SYNTH HOPES TO BE AT WCRTM
IN BOSTON IN APRIL 2021

15. STATUS QUO NOW
2002
2009
• Cell types & lab methods
stagnant for 20 years
• CKD & Dialysis-based
• Consensus-based classification
• Rising output, dropping cost of
scRNA-seq
• Increasing # of classified cell
types
• More data available for AI
*Data from the ASN
*Data from Svensson et al. Nat Protoc, 2018.

16. SINGLE-CELL SEQUENCING
• 47 novel, distinct cell subtypes in
mouse cerebral cortex &
hippocampus
• 6  12 subtypes of human blood
dendritic cells
• 21 distinct cell subtypes in mouse
kidneys; 3 novel types
• We predict the number of human
kidney cell subtypes will double
from 26  52
*Figure 3 from Lu et al. Kidney International, 2017.

17. MACHINE LEARNING: DATA
• Whole-Slide Imaging
• Humans & ML systems make different mistakes
• Computer programs can examine sub-visual features
• Computer-assisted diagnosis – Eventually computers will
write preliminary reports before we see slides!
• Solid organ transplant prognostication
• Massive multi-factor analysis using donor and recipient
history

18. MACHINE LEARNING: DATA
• Regenerative Medicine is All About Getting Right Cells in
Right Places
• Human Cell Atlas single cell transcriptomics identifies who
the cellular players are in the drama unfolding in
transplanted and tissue engineered organs.
• Success will require a combination of regenerative
medicine and artificial intelligence. Computational
biologists will be key.

19. FROM CONSENSUS TO BIOLOGY
• Banff Classification is the standard for solid organ transplant
pathology & biopsy interpretation
• Currently lacks external science validation although has
clinical validation
• Poor inter-pathologist agreement
• Consensus-based classification since 1991
• Current classification based on phenotypes, cell surface
markers, and morphology
• In future biology will tell its own story

20. APPLICATIONS
• Patient Care
• Pathology
• Computer Science
• AI
• Computational Biology
• Ethics
• Patients
• Every organ system

21. CONCLUSION
Every aspect of the
medical and healthcare
spheres will be affected
by Regenerative
Medicine and AI. Each
year Banff and TERMIS
will be more and more
about Regenerative
Medicine and AI.
Support WCRTM plans!

22. THANK YOU
Questions?