Dr. Kim Solez presents "Bridge between Transplantation and Regenerative Medicine" at the Banff Transplant Pathology meeting in Vancouver October 5, 2015. Copyright (c) 2015, JustMachines Inc.
2. I first spoke about the inevitable transition from
transplant pathology to tissue engineering
pathology at Banff 2011 in Paris, and Banff 2013
in Brazil, and then at length at the New Orleans
Pathology 2015 meeting in July 2015.
A paper in press in Critical Care Medicine references those
previous presentations and notes that many different
modalities of examination may be used to detect tissue
engineering pathology in the future including detection of
soluble biomarkers. Solez K; Multibiomarker Article Gives a
Taste of What the Era of Regenerative Medicine/Tissue
Engineering Pathology Will Be Like, Crit Care Med. (in press)
This presentation is the first definitive platform
presentation before a transplantation audience.
5. Worldwide 1.2 million people are in
need of transplantation for end
stage organ failure. Current
transplant protocols reach fewer
than 10% of this number.
Regenerative medicine can save the
remaining 90%, over one million
people annuallly!
6. ViaCyte Announces Highly
Anticipated Encapsulation Clinical
Trial Site Expansion into Canada
JDRF-funded researcher, Dr. James Shapiro
will be the lead investigator at the Canadian
site. TORONTO, July 29, 2015 -- ViaCyte, Inc.
announced the opening of a second site in its
Phase 1/2 trial for Type I Diabetes which utilizes
PEC-01™ pancreatic progenitor cells and the
proprietary Encaptra® drug delivery system which
is designed to protect the transplanted cells from a
patient’s immune system.
Regenerative Medicine Already Here!
Viacyte Trial for Diabetes Therapy.
7. Double Think: Stem Cells are Greatest Hope
and Greatest Hype, Stem Cell Tourism
Estimated to be $3 Billion a Year Industry and
Growing, with More than 700 Clinics Worldwide
Mason C et al. Regen Med. 2011 May;6(3):265-72. doi:
10.2217/rme.11.28. Cell therapy industry: billion dollar
global business with unlimited potential.
Timothy Caulfield - Stem Cell Tourism June 2015
https://www.youtube.com/watch?v=B0r89nMtg10
8. University of Alberta Health Law Institute
http://www.hli.ualberta.ca/en/Publications.as
px Stem cell Publications
Stem cell hype: Media portrayal of therapy
translation MARCH 30, 2015
Policy Options: Athletes and unproven stem cell
therapies JANUARY 01, 2015
Research ethics and stem cells Is it time to re‐think
current approaches to oversight? DECEMBER 04, 2014
9. University of Alberta Health Law Institute
http://www.hli.ualberta.ca/en/Publications.aspx
Stem cell publications continued
Representations of Stem Cell Clinics on
Twitter DECEMBER 01, 2014
Unproven stem cell-based interventions & physicians'
professional obligations; a qualitative study with
medical regulatory authorities in Canada. OCTOBER 14,
2014 Professional Regulation: A Potentially Valuable
Tool in Responding to "Stem Cell
Tourism" SEPTEMBER 09, 2014
10. University of Alberta Health Law Institute
http://www.hli.ualberta.ca/en/Publications.aspx
Stem cell publications continued
Stem Cell Tourism and Public Education: The Missing
Elements SEPTEMBER 04, 2014
Policy recommendations for addressing privacy
challenges associated with cell-based research and
interventions FEBRUARY 03, 2014 Commercialization
and Stem Cell Research: A Review of Emerging Issues
DECEMBER 20, 2013 A Role for Patient Advocacy
Groups in Countering the Premature Commercialization
of Stem Cell Interventions
OCTOBER 01, 2013
11. The Positive Aspects of Stem Cell Therapies,
The True Hope, Has Potential to Reverse Three
Looming Problems in Medicine:
1. The loss of “luster” in transplantation.
2. Workforce problems in nephrology due to lack of appeal
to young people/potential trainees worldwide.
3. Technological unemployment in medicine due to
12. “They will never be able to reverse those
trends.” Together we can do those things,
reverse those trends, make life good again!
1. The loss of “luster” in transplantation.
2. Workforce problems in nephrology due to lack of appeal
to young people/potential trainees worldwide.
3. Technological unemployment in medicine due to
14. 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.
15. 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
16. Significance of ‘Banff papers’
• More than 5,000 citations of the 14 Banff meeting reports
• 915 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
18. 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
19. 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
2015 Local Conference
chair: Michael Mengel
Organ Steering committee
Chairs:
Composite tissues: Linda Cendales
Heart : Patrick Bruneval
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 : Patrick Bruneval
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
30. Many problems with stem cell generate
organs not being discussed. Do not exclude
yourself from the conversation in this area!
31. 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
heparinized 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. Logo still works for future!
32. Transplant
pathologists will also
become tissue
engineering
pathologists,
pathologists who
analyze 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.
33. 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.
34. Beginning at the Very Beginning!
“We are at the very beginning of time for the human race. It
is not unreasonable that we grapple with problems. But
there are tens of thousands of years in the future. Our
responsibility is to do what we can, learn what we can,
improve the solutions, and pass them on.” - Richard P.
Feynman, (1918-1988) Physicist, Nobel Prize Winner
"The sense of the future is behind all good policies. Unless
we have it, we can give nothing either wise or decent to
the world." - Snow CP, (1905-1980) Novelist and
Philosopher.
"To a large extent, the future lies before us like a vast
wilderness of unexplored reality. The God who created and
sustained the evolving universe through eons of progress
and development has not placed our generation at the tag
end of the creative process. God has placed us at a new
beginning. We are here for the future." - Sir John
Templeton (1912-2008 ), Financial Analyst
35. Beginning at the Very Beginning!
Like 1851 when the first International Classification of
Diseases was presented in the Grand Exhibition of
Technology at London’s Crystal Palace
Emphasis was on cause of death
36. Classification focus is on sustaining life.
Native and transplanted organ diseases can also occur in
tissue engineered organs.
The classification focus of the new pathology discipline of
Regenerative Medicine/Tissue Engineering Pathology is
exactly the opposite of traditional classification of disease
which starts with causes of death. In Regenerative
Medicine/Tissue Engineering Pathology the emphasis is on
the degree of normality necessary to sustain life:
Normal,
Abnormalities of unknown functional significance,
Abnormalities which will impair the main functions of the
organ,
Abnormalities leading to severe organ dysfunction where
function may not be great enough to sustain life.
37. Song et al. Interstitium, vessels, and glomeruli with missing cells.
Disordered tubule formation with multiple interconnecting
lumina of differing sizes. “Can you really call this a kidney?” (Yes!)
38. Song et al. In addition to missing cells and disordered structures,
you have cells in the wrong places. Podocytes in the interstitium.
39. Focus of Tissue Engineering Pathology
The specific questions become: 1. Are too many cells
missing, 2. Are too many cells in in the wrong places? 3.
Are too many structures missing (long loops of Henle)?
4. Is there too much endothelial disruption for the organ
to be properly perfused? 5. What are the risks of
neoplastic transformation?
Classification categories should be not one-off, but
reproducible, generalizable.
Tissue engineering pathology has been up to now really
dull (articles since 1967), since most reports were of
scaffolds with no inflammatory reaction "Move along,
nothing to see here" pathology, but from today becomes
really exciting with novel morphological changes and
lives hanging in the balance, clinical trials starting!
Banff Classification of Tissue Engineering Pathology
major focus 2017 meeting in Spain and 2019 in Turkey.