Dr. Kim Solez presents Transplantation Pathology, Regenerative Medicine, and Where We Go From Here at the Nephrology Core Lecture Series on January 7th, 2015 at the University of Alberta in Edmonton, Canada. See https://www.youtube.com/watch?v=5wfdhB_VyJw

1. Kim Solez, MD

2. Future Concepts
 Machines are becoming
exponentially smarter than we
are. Will be smarter than an
individual human in 2029 and
smarter than the whole human
race in aggregate in 2045.
 Machines will replace most
human labor in the next thirty
years.

3. Nephrologists May Be Only People
Still Employed in 2045!

4. Who Am I?

5. Who Am I?

7. Banff Classification of Kidney Transplant Pathology
Histologic criteria for the diagnosis of rejection and
other conditions in the transplanted kidney, began
1991, updated and expanded every two years in
consensus meeting.

8. BANFF Classification Standard For
Transplant Biopsy Interpretation
• Began in kidney (Solez
et al. 1993), and was
then extended to liver,
pancreas, composite
tissue grafts etc.
Meetings also
consider heart, lung,
small bowel.
• Uses semi-
quantitative lesion
scoring 0-3+ and
diagnostic categories.

9.  1991 First Conference
 1993 First Kidney International publication
 1995 Integration with CADI
 1997 Integration with CCTT classification
 1999 Second KI paper. Clinical practice guidelines. Implantation biopsies.
 2001 Classification of antibody-mediated rejection: Regulatory agencies
participating
 2003 Genomics focus, ptc cell accumulation scoring
 2005 Gene chip analysis. Elimination of CAN, identification of chronic
antibody-mediated rejection.
 2007 First meeting far from a town called “Banff” – La Coruna, Spain.
 2009 Working groups. Meeting in Banff, Alberta, Canada
 2013 Establishment of Banff Foundation for Allograft Pathology

10. Significance of ‘Banff papers’
• 4244 citations of the 9 Banff meeting reports
• 790 Banff / Transplantation papers in PubMed
• Banff 2003 meeting report (ABMR criteria) = most cited AJT
paper
• 3 Banff meeting reports are among the top 4 cited AJT articles

11. Genomics Versus Traditional Pathology. Banff Schema Will
Ultimately Incorporate Both, Banff Phase II.
 Genome Canada
transplant transcriptome project.
 Traditional pathology techniques.
Affymetrix GeneChip® probe array.
Image courtesy of Affymetrix.

12. BANFF Governance
Structure -
• Until 2013 we have
had none beyond
Drs. Racusen and
Solez.
• Formed Swiss
foundation legal
entity in 2013, to
enable us to enter
into formal
relationships with
other organizations
we could not do
before..

13. Organizational structure of the Banff Foundation For Allograft Pathology
Board of Trustees:
K. Solez (Chair), L. Racusen, D. Glotz, J. Demetris, M. Mengel, M. Mihatsch, D. Seron, N.
Schmidt
2015 Local Conference
chair: Michael Mengel
Organ Steering committee
Chairs:
Composite tissues: Linda Cendales
Heart : Rene Rodriguez
Kidney: Mark Haas
Liver: Jake Demetris
Lung: William Wallace and Carol
Farver
Pancreas: Cinthia Drachenberg
Banff Working Group (BWG) Leads:
Molecular transplantation pathology: Michael Mengel, Banu Sis
Isolated v-lesions: Banu Sis, Ed Kraus
Quality assurance in transplantation diagnostics: Michael Mengel and
Parmjeet Randhawa
C4d-negative ABMR: Mark Haas, Banu Sis, Alexandre Loupy
Fibrosis scoring: Robert Colvin, Brad Farris, Michael Mengel
Digital Pathology in Transplantation: Jake Demetris
2015 Scientific program committee:
Alex Loupy (Chair)
Mark Haas, Banu Sis, Kathryn Tinkham, Candice
Rofousse, Chris Bellamy, Lynn Cornell, Carmen
LeFaucheur
Composite tissues: Linda Cendales
Heart : Rene Rodriguez
Liver: Jake Demetris
Lung: William Wallace and Carol Farver
Pancreas/Islets: Cinthia Drachenberg and John
Papadimitriou
Secretary/Treasurer:
Michael Mengel
funding
collaboration
reports to
reports to
collaboration
collaboration
reports to
collaboration
progress
reports to Budged
proposal and
accountability
for meeting
costs
support

16. Target Audience for the 2015 joint
CST/Banff meeting: total ~600 expected
delegates
 Basic Scientists
 Pathologists
 Immunogeneticists and HLA experts
 Transplant Physicians: Internal Medicine, Surgery,
Infectious Diseases, Critical Care
 Allied Health Care
 Students, Trainees, Fellows

17. The Banff Process
Consensus communication in renal transplantation
a
The Banff
lesions
g, i, t, v - score
The Banff
community
Pathologists
Nephrologists
Tx-Surgeons
Lab-Medicine
established by
consensus in 1991
The Banff
classification
Current consensus for
diagnostics
moderated
Banff meetings
thesis-antithesis-synthesis
tentative
thresholds
participate
refinementBanff Working
Groups
Feedback concerning weaknesses and strengths by results
from independent research
New members
Biostaticians
Molecular Biologists
“Omics”-specialists
Off-springs
Liver
Pancreas
Lung, Heart
CTA

18. The Banff Schema was first developed
at a meeting of pathologists, clinicians
and surgeons in Banff, Alberta, Canada,
August 2-4, 1991 and has become the
worldwide standard for the interpretation
of transplant biopsies.

19. The Banff Schema was first developed
at a meeting of pathologists, clinicians
and surgeons in Banff, Alberta, Canada,
August 2-4, 1991 and has become the
worldwide standard for the interpretation
of transplant biopsies.

21. Moore’s Law&Eroom’s Law , the
technological Singularity and
exponential change, exponential
decline in # new drugs per
billion dollars R&D expenditure.

22. The Technological
Singularity

23. The World is Changing Rapidly! Banff
Phase III Regenerative Medicine

24. The World is Changing Rapidly!

25. The World is Changing Rapidly!

26. The World is Changing Rapidly!

27. Perfused 7 days without oxygen or
nutrients! Of course no nuclei seen!

28. Canadian Data on Public Interest in
Regenerative Medicine

29. Podocytes go wandering into the
interstitium! Song et al.

30. The Banff Foundation for Allograft Pathology
Must Remain Youthful and Relevant for the
Future – Must Adapt, Plan for Changes
 As the field changes and stem-cell-grown organs replace
transplantation, the organization must change with it
 Transplantation may be loosing its luster but luster of the
Banff Foundation for Allograft Pathology can remain
strong.
 As an exercise in alternative realities I asked participants
to consider the very different life of David Crippen, my
counterpart in critical care medicine. We need to consider
changes that large!

31. The spectacular dynamics influencing the
pace of stem generation of organs replacing
transplantation in the future.
 There were YouTube videos (now removed) suggesting
that stem cell generation of complex organs in humans
would be routine by 2020. Problems of clotting, endothelial
loss, and cell type selection errors not mentioned.
 The dramatic slowdown of new drug approvals (Eroom’s
Law) by the FDA suggests that the FDA is ripe for
disruptive innovation. Has happened.
 However stem cell therapies may be the last area the FDA
will relax regulation in, as unproven bogus stem cell
therapies are causing widespread suffering and protection
of the general public is needed.

32. Many problems with stem cell generate
organs not being discussed. Do not exclude
yourself from the action in this area!

33. Many problems with stem cell generate
organs not being discussed. Need to get
those conversations to happen.
 The recellularized organ clots like crazy, impossible to
regenerate more than 80% of endothelial surface. Artificial
heparized surface not fenestrated. Cell traffic abnormal.
 Hard to get right types of cells to right places.
 Podocytes seems to be terminally differentiated cells,
when attempt to culture them they turn into different type of
cell.
 Kidney progenitor stem cell difficult to identify, kidney work
has lagged behind.
 Easy to make stem cell generated kidneys that lack loop of
Henle. Could produce lethal polyuria. What is “function”?
 Many old fashioned questions of physiology about how the
stem cell generated organ works, not just true for kidney,
true for every organ.

34.  Transplant
pathologists will also
become tissue
engineering
pathologists,
pathologists who
analyse organs grown
from stem cells. This is
not something beyond
us, we can adapt to a
work life that includes
stem cells.. Someone
needs to cross the
disciplines,

35.  Many of the questions
that need to be posed
about stem cell
generated organs are old
fashioned questions,
intact nephron
hypothesis, cell
regeneration, stunned
myocardium, contraction
band necrosis etc. Use
your nostalgia! Stimulate
conversations between
stem cell researchers and
transplant physicians.