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Introduction to Regenerative Medicine
Kim Solez, MD
If the subject of this talk interests you and you want to continue the conversation, there are two excellent ways to do that:
1. Vancouver Combined Banff CST Meeting Oct. 5-10, 2015
http://www.banfffoundation.org
2. Technology and Future of Medicine Course LABMP 590
Starts Sept 1st Tuesday and Thursdays 2-3:20 CCIS L1-140 Special 6 pm sessions in eHub, Hub Mall 9007 on Sept 3rd, 8th, and 10th http://www.singularitycourse.com
Stem Cell Technologies on Google Trends – News Headlines and Forecast
Current transplant protocols reach fewer than 10% of those in need.
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!
For the first time, a patient has received a synthetic windpipe (trachea) that was created in a lab with the patient's own stem cells.
Regenerative Medicine Already Here! Working for Tubular Organs, Bladder, Trachea, Esophagus, Vagina.
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.
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 2015https://www.youtube.com/watch?v=B0r89nMtg10
University of Alberta Health Law Institutehttp://www.hli.ualberta.ca/en/Publications.aspx Stem cell Publications
Stem cell hype: Media portrayal of therapy translationMARCH 30, 2015 Policy Options: Athletes and unproven stem cell therapiesJANUARY 01, 2015
Research ethics and stem cells Is it time to re‐think current approaches to oversight?DECEMBER 04, 2014
University of Alberta Health Law Institutehttp://www.hli.ualberta.ca/en/Publications.aspx Stem cell publications continued
Representations of Stem Cell Clinics on TwitterDECEMBER 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
University of Alberta Health Law Institutehttp://www.hli.ualberta.ca/en/Publications.aspx Stem cell publications continued
Stem Cell Tourism and Public Education: The Missing ElementsSEPTEMBER 04, 2014 Policy recommendations for addressing privacy challenges associated with cell-based research and interventionsFEBRUARY 03, 2014 Commercialization and Stem Cell Research: A Review of Emerging IssuesDECEMBER 20, 2013A Role for Patient Advocacy Groups in Countering the Premature Commercialization of Stem Cell InterventionsOCTOBER 01, 2013
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 replacement of human workers by machines.
“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 replacement of human workers by machines.
Nephrologists & Renal Pathologists May Be Only People Still Employed in 2045!
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.
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
BANFF Classification - Milestones
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
Tissue Engineering Pathology Added Soon!•
The Banff ProcessConsensus communication in renal transplantation
a
The Banff lesions
g, i, t, v - score
The Banff communityPathologistsNephrologistsTx-SurgeonsLab-Medicine
established by
consensus in 1991
The Banff classificationCurrent consensus for diagnostics
moderatedBanff meetings
thesis-antithesis-synthesis
tentative
thresholds
participate
refinementBanff Working Groups
Feedback concerning weaknesses and strengths by results from independent research
New membersBiostaticiansMolecular Biologists“Omics”-specialists
Off-springsLiverPancreasLung, HeartCTA
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 CendalesHeart : Patrick BrunevalKidney: Mark HaasLiver: Jake DemetrisLung: William Wallace and Carol FarverPancreas: Cinthia Drachenberg
Banff Working Group (BWG) Leads: Molecular transplantation pathology: Michael Mengel, Banu SisIsolated v-lesions: Banu Sis, Ed KrausQuality assurance in transplantation diagnostics: Michael Mengel and Parmjeet RandhawaC4d-negative ABMR: Mark Haas, Banu Sis, Alexandre LoupyFibrosis scoring: Robert Colvin, Brad Farris, Michael MengelDigital 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 LeFaucheurComposite tissues: Linda CendalesHeart : Patrick BrunevalLiver: Jake DemetrisLung: William Wallace and Carol FarverPancreas/Islets: Cinthia Drachenberg and John Papadimitriou
Secretary/Treasurer: Michael Mengel
funding
collaboration
reports to
reports to
collaboration
collaboration
reports to
collaborationprogress reports to Budged
proposal and accountability for meeting costs
support
BANFF Conferences On Allograft Pathology 1991-Forever?
The World is Changing Rapidly!
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
The Technological Singularity
Podocytes go wandering into the interstitium! Song et al.
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.
Banff Foundation for Allograft Pathology and Banff Meetings Must Adapt to Future Changes in Field of Transplantation
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,
It is OK to Allow the Natural Resistance to Change and Nostalgia for the Past to Motivate You!
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.
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
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
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.
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!)
Song et al. In addition to missing cells and disordered structures,you have cells in the wrong places. Podocytes in the interstitium.
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?
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)
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)
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!
In our original location we had mule deer poking their heads
into the meeting rooms!We’ve come a long way!
An Afterthought: The pathologist’s continuity of care, Self-aware artificial intelligence could insert itself at any point! “Why don’t you let me do it?”
The pathologist’s continuity of care, Self-aware artificial
intelligence could insert itself at any point!
The pathologist’s continuity of care, Self-aware artificial
intelligence could insert itself at any point!
The pathologist’s continuity of care, Self-aware artificial
intelligence could insert itself at any point!
The pathologist’s continuity of care, Self-aware artificial
intelligence could insert itself at any point!
The pathologist’s continuity of care, Self-aware artificial
intelligence could insert itself at any point!
Rich Sutton (UAlberta) Future of AI meeting Puerto Rico Jan
3, 2015
Acceptance. Share power. The AIs will not all be under our control. They will compete and cooperate with us just like other people, except with greater diversity and Asymmetries We need to set up mechanisms (social, legal, political, cultural) to ensure that this works out well Inevitably, conventional humans will be less important. Step 1: Lose your sense of entitlementStep 2: Include AIs in your circle of empathy Thought provoking for us all!