Dr. Kim Solez TEP meets Human Cell Atlas Project, a glimpse into future of pathology, Technology and Future of Medicine course February 15, 2018 http://www.singularitycourse.com Copyright (c) 2018, JustMachines Inc.

1. Kim Solez, MD

2. Stem Cell Technologies on Google
Trends – News Headlines and Forecast

3. Current transplant protocols reach
fewer than 10% of those in need.

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.  Tissue engineered bladder.
Regenerative Medicine Already Here!
Working for Tubular Organs, Bladder,
Trachea, Esophagus, Vagina.

6. Tissue Engineering Pathology: Am.
Journal of Transplantation Feb. 2018

7. Something Missing In the Concept of
Tissue Engineering Pathology: The
Numbers – How Many Cells – How
Many Conditions Can Be Treated

8. Human Cell Atlas Begins to Answer
This: Was thought there were 300+
Main Cell Types in Human Body – 26
in Kidney (Al-Awqati and Oliver,2002)

9. Human Cell Atlas Begins to Answer
This: Studies in dendritic cells
suggest number of cell types will at
least double through HCAP analysis,
kidney cell types will go from 26-52.

10. So the Hitchhikers Guide to the
Galaxy is Off by Ten, the Meaning of
Life, the Universe, and Everything is
52 not 42

11. Human Cell Atlas Begins to Answer
This: 300+ Main Cell Types in Human
Body – 1000s of subtypes

12. Human Cell Atlas Begins to Answer
This Numbers Question: Analysis is
Inexpensive and Fast

13. Human Cell Atlas Begins to Answer
This Numbers Question: Analysis is
Inexpensive and Fast

14. Human Cell Atlas Already Leading to
Disease Insights Variants, Acting on
Them = Pathology

15. Human Cell Atlas Already Leading to
Disease Insights Variants, Acting on
Them = Pathology

16. Human Cell Atlas Pace of Change
Considerably Exceeds Moore’s Law

17. Human Cell Atlas Pace of Change
Considerably Exceeds Moore’s Law

18. Human Cell Atlas Pace of Change
Considerably Exceeds Moore’s Law

19. Human Cell Atlas Pace of Change
Considerably Exceeds Moore’s Law

20.  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.

21. 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

22. University of Alberta Health Law Institute
http://www.hli.ualberta.ca/en/Publications.as
px Stem cell Publications
 Combatting Unlicensed stem Cell interventions through
truthful advertising law: a survey of regulatory trends
January 3, 2017
 From Kim Kardashian to Dr. Oz: The Future Relevance of
Popular Culture to Our Health and Health Policy
October 26, 2016

23. 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


24. University of Alberta Health Law Institute
http://www.hli.ualberta.ca/en/Publications.as
px Stem cell Publications
 Media portrayal of non-invasive prenatal testing: a
missing ethical dimension MARCH 04, 2016
 Marginally scientific? Genetic testing of children and
adolescents for lifestyle and health
promotion JANUARY 15, 2016
 Trafficking in Human Beings for the Purpose of Organ
Removal and the Ethical and Legal Obligations of
Healthcare Providers January 4, 2016

25. 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

26. 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

27. 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

28. 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

29. “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

30. Nephrologists & Renal Pathologists May
Be Only People Still Employed in 2045!

31. 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.

32. 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

33.  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

34. 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

35. Tissue Engineering Pathology Added Soon!
•

36. 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

37. 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

40. The World is Changing Rapidly!

41. The World is Changing Rapidly!

42. The World is Changing Rapidly!

43. The World is Changing Rapidly!

44. Perfused 7 days without oxygen or
nutrients! Of course no nuclei seen!

45. Canadian Data on Public Interest in
Regenerative Medicine

46. The Technological
Singularity

47. Podocytes go wandering into the
interstitium! Song et al.

48. Many problems with stem cell generate
organs not being discussed. Do not exclude
yourself from the action in this area!

49. 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.

50.  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,

51.  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.

52. 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

53. 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

54. 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.

55. 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!)

56. Song et al. In addition to missing cells and disordered structures,
you have cells in the wrong places. Podocytes in the interstitium.

57. 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?

58. 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)

59. 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)

60. 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!