Confronting the Question of Stem Cells and the Future

of Transplantation Kim Solez, MD

Who Am I?

Who Am I?

Twenty-three years ago Kim Solez and Lorraine Racusen presided over a unique Meeting in Banff Canada.

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’• 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

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 CendalesHeart : Rene RodriguezKidney: 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 : Rene RodriguezLiver: 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?

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 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

The Banff Allograft Pathology Meetings Are Sometimes Said to be the “Best Meetings In Transplantation”. How Can This Possibly Be So?

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.

What People Mean is that They Like the Size, Atmosphere, Spirit, and Productivity of the Banff Meetings. These Attributes Must be Maintained.

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.

Dunbar’s Number of 150 People You Can Have Significant Empathetic Friendships With. Need to Maintain This Intimate Feeling in A Larger Meeting of 600.

Future ConceptsMoore’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 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.

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.

Turtles All

the Way

Down abstrusegoose.com/155

Animal Analogies

Limited.Need Human

Alter Egos

CCM-L Characters Off-Topic

DiscussionsNEPHROL

No CharactersNo Off-Topic Discussions

Many Military Awards, Karate

Black BeltNo Civilian AwardsNever Served in

MilitaryMany Civilian

Awards

Rock BandMotorcycles

Colorful History in 60’s and 70’s

No Band orMotorcycle

Boring Young Person

Crippen A Myth?

Proves the Metaphor

Works!

In our original location we had mule deer poking their heads

into the meeting rooms!We’ve come a long way!