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Kim Solez Transition transplant path to tissue engineering path new banff

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Dr. Kim Solez Presents "Transition Between Transplant Pathology and Tissue Engineering Pathology: Beginning A New Banff Classification" at the Alberta Transplant Institute Fellows Lecture Series January 10, 2017 at the University of Alberta in Edmonton, Alberta, Canada. Copyright (c) 2017, JustMachines Inc.

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Kim Solez Transition transplant path to tissue engineering path new banff

  1. 1. Kim Solez, MD
  2. 2. Stem Cell Technologies on Google Trends – News Headlines and Forecast
  3. 3. Current transplant protocols reach fewer than 10% of those in need.
  4. 4. 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 annually!
  5. 5.  Tissue engineered bladder. Regenerative Medicine Already Here! Working for Tubular Organs, Bladder, Trachea, Esophagus, Vagina.
  6. 6.  https://3dprintingindustry.com/news/organovo-3d- bioprinted-liver-tissue-make-fda-2019-101775/ Regenerative Medicine Already Here! 3D printed Liver Tissue May Be Ready for FDA approval in 2019.
  7. 7.  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.
  8. 8. 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
  9. 9. University of Alberta Health Law Institute http://www.hli.ualberta.ca/en/Publications.as px Stem cell Publications  Science, Celebrities, and Public Engagement Timothy Caulfield and Declan Fahy on Science, Celebrities, and Public Engagement in the Summer 2016 Issues in Science and Technology. www.issues.org JUNE 16, 2016  Science: Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines. MAY 13, 2016 
  10. 10. University of Alberta Health Law Institute http://www.hli.ualberta.ca/en/Publications.as px Stem cell Publications  Science: Confronting stem cell hype Professor Timothy Caulfield co-authors new stem cell policy guidelines. MAY 13, 2016  Stem cell hype: Media portrayal of therapy translation MARCH 30, 2015 Policy Options: Athletes and unproven stem cell therapies JANUARY 01, 2015
  11. 11. University of Alberta Health Law Institute http://www.hli.ualberta.ca/en/Publications.aspx Stem cell publications continued Research ethics and stem cells Is it time to re‐think current approaches to oversight? DECEMBER 04, 2014 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
  12. 12. 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
  13. 13. 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
  14. 14. “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
  15. 15. Nephrologists & Renal Pathologists May Be Only People Still Employed in 2045!
  16. 16. 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.
  17. 17. Banff Lesion Scoring: Sign of Educated Tx Pathologist imprimatur 1. The formula (=‘let it be printed’), signed by an official authorizing printing of a book;hence as sb. an official license to print. The Oxford English Dictionary (2nd. ed.) Banff lesion scoring: g cg i ci t ct v cv ah mm ptc C4d
  18. 18.  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
  19. 19. Significance of ‘Banff papers’ • More than 5,000 citations of the 14 Banff meeting reports • 977 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
  20. 20. Tissue Engineering Pathology Added Soon! •
  21. 21. 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
  22. 22. 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
  23. 23. The World is Changing Rapidly!
  24. 24. The World is Changing Rapidly!
  25. 25. The World is Changing Rapidly!
  26. 26. The World is Changing Rapidly!
  27. 27. Perfused 7 days without oxygen or nutrients! Of course no nuclei seen!
  28. 28. Canadian Data on Public Interest in Regenerative Medicine
  29. 29. The Technological Singularity
  30. 30. Podocytes go wandering into the interstitium! Song et al.
  31. 31. Many problems with stem cell generate organs not being discussed. Do not exclude yourself from the action in this area!
  32. 32. 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.
  33. 33.  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,
  34. 34.  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.
  35. 35. 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
  36. 36. 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
  37. 37. 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.
  38. 38. 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!)
  39. 39. Song et al. In addition to missing cells and disordered structures, you have cells in the wrong places. Podocytes in the interstitium.
  40. 40. Focus of Tissue Engineering Pathology  The focus of tissue engineering pathology will shift to the question: “Is this organ structurally intact enough to function safely and adequately in the recipient?” Using the kidney as an example, the specific questions become: (Images by Korey Fung)  1. Are there too many missing cells, distorted structures for the organ to function adequately?
  41. 41. Focus of Tissue Engineering Pathology  The focus of tissue engineering pathology will shift to the question: “Is this organ structurally intact enough to function safely and adequately in the recipient?” Using the kidney as an example, the specific questions become: (Images by Korey Fung)  2. Are there too many cells in the wrong places (e.g. podocytes in the interstitium)
  42. 42. Focus of Tissue Engineering Pathology  (Images by Korey Fung)  3. Are there missing/distorted structural elements that represent a risk to the patient? (missing loops of Henle causing lethal polyuria)
  43. 43. Focus of Tissue Engineering Pathology  Using the kidney as an example, the specific questions become:  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, 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!
  44. 44. Khouloud Saliba and I Presented These Ideas at TERMIS (Regenerative Medicine) Meeting in San Diego Dec. 11-14, 2016.
  45. 45. Met Astgik Petrosyan Who Has Written About the Many Additional Variables Which Will Add Complexity to New Banff Classification  Decellularized Renal Matrix and Regenerative Medicine of the Kidney: A Different Point of View Petrosyan Astgik, … and Perin Laura. Tissue Engineering Part B: Reviews. May 2016, 22(3): 183- 192.  A Step Towards Clinical Application of Acellular Matrix: A Clue from Macrophage Polarization. Petrosyan A, …Perin L. Matrix Biol. 2016 Aug 26. pii: S0945-053X(16)30133-0.
  46. 46. Astgik Petrosyan Variables Will Necessitate AI Approaches to New Banff Classification!

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