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Kim Solez Transplant Pathology Regen Med 2015

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Kim Solez ,
Kim Solez ,

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

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Kim Solez, MD
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.
Nephrologists May Be Only People Still Employed in 2045!
Who Am I?
Who Am I?
Kim Solez Transplant Pathology Regen Med 2015
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.
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.
 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
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
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.
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..
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
Kim Solez Transplant Pathology Regen Med 2015
Kim Solez Transplant Pathology Regen Med 2015
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
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
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.
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.
Kim Solez Transplant Pathology Regen Med 2015
Moore’s Law&Eroom’s Law , the technological Singularity and exponential change, exponential decline in # new drugs per billion dollars R&D expenditure.
The Technological Singularity
The World is Changing Rapidly! Banff Phase III Regenerative Medicine
The World is Changing Rapidly!
The World is Changing Rapidly!
The World is Changing Rapidly!
Perfused 7 days without oxygen or nutrients! Of course no nuclei seen!
Canadian Data on Public Interest in Regenerative Medicine
Podocytes go wandering into the interstitium! Song et al.
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!
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.
Many problems with stem cell generate organs not being discussed. Do not exclude yourself from the action in this area!
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.
 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,
 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.
Kim Solez Transplant Pathology Regen Med 2015

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Kim Solez Transplant Pathology Regen Med 2015

  • 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!
  • 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.
  • 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.