Sebastian Giwa, PhD, NASA Research Park Cell:+1-857-222-6669 Organ Preservation Alliance Building 20, S. Akron Road [email protected] Co-Founder, President & CEO Moffett Field, CA 94035n Alliance organpreservationalliance.org
For Immediate Release:
World-Leading Surgeons, Scientists and the Organ Preservation Alliance Applaud Defense Department Initiated First-Ever Government Grant Programs Targeting Organ Cryobanking for Transplants
December 22, 2014, NASA Research Park, Moffett Field, CA – The Organ Preservation Alliance, a Silicon Valley nnonprofitonprofit working to savsavee millions of lives by catalyzingcatalyzing breakthroughs in the storagestorage of organs, together with world-leadingworld-leading transplant surgeons and scientists on the Alliance’sAlliance’s medical and scientific advisory boards, jointly ccongratulateongratulate the U.S.U.S. Department of Defense (DoD) on its announcement of the first-ever multi-million dollar grant funding poolspools dedicated to research on organ and tissue banking technologiestechnologies..
On January 15, 2015, the DoD will open three separaseparate,te, but complementarycomplementary,, organ cryopreservationcryopreservation grant programs. These programs could together fund research for 20 or moremore leading American research teams,teams, with strong, individual teamsteams potentially receiving $3-3.5 million across different phase 1 and 2 awards. These business innovation (SBIR) grantgrantss aaimedimed to support U.SU.S.. commercialization of science while achieving militamilitaryry health goals.
Sebastian Giwa, PhDPhD,, President and CEO of the Organ Preservation Alliance,Alliance, said:
“This bold step by the DoD will enable the crcrucialucial breakthroughs needed to create a future in whichwhich we can stop biological time for human organs, in much the way that we have, for decades, been able to bank stemstem cells, human eggs, sperm and embryos.”
“35% of all deaths in the UU.S..S. could be prevented or substantiallysubstantially delayed by organ transplantation, and this move by the DoD could be a true ggameame changer.”
“In the context of the huge investments the DoD is making in tissue engineering via the Armed Forces Institute of Regenerative Medicine (AFIRM), and the investments in the world’s largest hand and face transplant program, this investment in cryopreservation will not only add value on its own by improving current transplantation practices, but will support, complement and accelerate tissue engineering breakthroughs.”
Need for Organs is Vast, DoD Funding Could Transform Transplantation and Save Millions of Lives
“The supply of tissues is one of the major constraints we face in transplantation medicinemedicine todatodayy,, and organ banking technology would dramatically help rresolveesolve it. This is a majomajorr step forward in the fieldfield of transplantation,” sasaidid Harvard Medical School Professor Bodhan PomahacPomahac..
“Currently“Currently,, transplant organs cannot be stored for long at alall,l, so a high percentage of viable transplant organs are disdiscardedcarded before matches can be found and helicopter and jet transportation can be arranged. Hearts, for instance, can currently only survive for 4-5 hours outside of a body,”body,” said world-leading heart transplant surgeosurgeon,n, ProfessorProfessor JJacobacob Lavee. “If we could get longer preservation, so that just half of the wasted hearts and lungs could be used, the U.S. wait-list for these organs would be extinguished iinn a few
years.”
Dr. Gerald Brandacher, Scientific Director of the Composite Tissue AllotraAllotransplantationnsplantation Program at JohnsJohns Hopkins heralded this commitment: “People seem to underestimate what coulcouldd be comingcoming.. This is a big step towards a future in which we routinelyroutinely
replace damaged organs and tissues to restore both form and function, in aa way that only transplantation allows – replacing ‘like with like’.” “The ability to build real organ and tissue banks ccouldould transform the entire field of trtransplantation.ansplantation. This commitment from the DoD is taking us one step closer to that reality.”” reality.
The DoD’s Three Separate, but Complementary, Grant Programs are Designed to Catalyze Audacious Breakthroughs
The three new DoD grant programs target different, but related, proproblemsblems in the field. The first progprogramram aims to develdevelopop fundamental breakthroughs in the low temperaturtemperaturee physicsphysics underlying the preservation of living tissues;tissues; the second programs focuses on low toxicity cryoprotectants that prevent ice formation in cooled organs; and the third program targets effective and fast rewarming protocols to ‘out-warm’ the ice cryscrystallizationtallization process and for restoring functionfunction to cooled organs.
“At first look, the challenge of reversible banking of human organs seems daunting, but it can be broken down into a set of tractable sub-problems, each with many potential solutions. The different topics that the DoD is asking scientists to work on to a large extent cover the set of different sub-challenges that need to be overcome," said leading cryobiologist, Professor Boris Rubinsky at UC Berkeley.
Military as well as Civilian Needs Outside of Vital Organs are Immense
“The DoD’s decision to support tissue cryopreservation research is critical to restoring the health and function of our brave service members,” said world-leading cryobiology scientist Mehmet Toner, Professor at Harvard, Mass General and MIT.
"Progress in cryobanking would be game-changing and would enable our ever-improving transplantationtransplantation abilitiesabilities to help maimed
AmericanDr. WP Andrew servicemen, Lee, who as well performed as firefightersfirefighters, the nation’nation’s, factoryfactorys first workersworkers, military, or double-arm civilians and transplants children aroundaro andund is DireDirectorthe worldctor of injureinjured the Departmentd by landmines,landmines,”” of said Plastic & Reconstructive Surgery at Johns Hopkins.Hopkins.
Dr. Lee’Lee’ss colleague, Dr. Pomahac at Harvard said: said: “In addition to scarce availability of vital organs like heart and kidneys, there is a tremendous lack of vascularized composite tissues forfor transplantation, trauma, reconstructive and regeregenerativenerative medicine needsneeds.. Over 1,600 service members have suffered amputations from injuries in Iraq and Afghanistan and over 4,000 Service members have sustained severe craniomaxillofacial injuries. Being able to bank complex vascularized tissue wouwouldld revolutionizerevolutionize the way we can restore these brave young women and men who serve our country.country.””
At the same time that the nnumberumber of catastrophic combat injuriesinjuries to limbs and face is unacceptablyunacceptably high, civiliaciviliann need for solutions to amputations is even greater: “Tw“Twoo million people are living with limb loss in the UU.S.,.S., with 185,000 amputations coconductednducted each year. ApproximatApproximatelyely 100,000 of those amputations stem from vascular disease and/or diabetes, and roughly 83,000 are due to trauma, often in young individuals,”individuals,” Dr. Lee added.
Decades of Cryobiology Research, as well as Valuable Understanding and Tools in Other - Often Radically Accelerating - Domains Have Set the Stage for the Needed Breakthroughs
“It is wonderful that the DoD has decided to target complex system cryopreservation at this moment in time. Cryobiologists have been able to preserve individual cells and a wide variety of organized tissues for decades, and even intestinal segments, whole uteri, and to some extent whole ovaries, by freezing. And exiting progress, including my group’s ability to cryopreserve and successfully transplant a rabbit kidney, with subsequent life support, by avoiding ice formation entirely, suggests that much more extensive successes may be possible in the future,” said Dr. Greg Fahy, Chief Science Officer at 21st Century Medicine.
“With all the possibilities cryopreservation research has opened upup,, there is now a lot of room for scientists in other fields to come in and apply their knowledge. As a result, we may bbee on the path to better cryoprotectantcryoprotectants,s, better rewarming techniques, better tools in almost every respect,” said Dr. Erik WWoodsoods,, President of the International Society of Cryobiology.
Important Move by the DoD in to Ensure that the U.S. does Not Fall Behind China; Large Commercial Value
"China has been making progprogressress lately in the field.field. The other day, I read a studystudy about an experiment iinn which Chinese scientists cryopreserved rat legs and successfully transplantedtransplanted them into recipient rants. It is a shame that China beat us to these important
proof-of-concept results, when the U.S. has arguably the best scientists in the world when it ccomesomes to cryopreservation.cryopreservation. The decision by the DoD to help support these scientistscientistss is a great step in the right direction,”said Harvard MedMedicalical School ProfessorProfessor Bodhan Pomahac.
"Even in the applications where cryopreservation is already clinically avavailableailable — the banking of cells and simple tissues — progress in organ preservation will lead to better techniques. The market value of these areas is large,large, and progress in them will inin turn lead to further cryopreservation investment. Because of this, targeting organ preservation pushes the overaoverallll field of regenerative medicine forwforward,"ard," said President and Chief Science Officer of Cell & Tissue Systems, Dr. KelviKelvinn BrockbanBrockbankk
Protecting Ovaries of Women with Cancer; Accelerating Drug Development With Less Animal Experiments
"One huge potential application for this technology will be in helping patients who have treatabletreatable cancer, but requirerequire strong doses of of chemo or radiation therapytherapy.. In these cases, cryobankingcryobanking could enable doctors to protect crucially important,important, but fragile, tissuestissues by removing them, banking them and then transplanting them back into the patient after the gonadotoxic therapy is completed."completed." says world leader in ovary cryopreservation and Professor Pasquale Patrizio, Director of the Yale UniversityUniversity Fertility Center
“Preserving human tissues for research on a broad range of diseases will facilitate and accelerate scientific advances and create impact at the clinic. It can also potentially reduce costs and decrease the need for animals in research. In a similar way, it will also aid drug screening and development reducing cost and time towards new therapies,” Professor Utkan Demirci, Director of Stanford University’s Bio-Acoustic MEMS in Medicine Labs.
"The power of cryopreservation stems from the universality of breakthroughs in one complex tissue system to others. What we learn in preserving liver tissue will help us preserve limb and the knowledge gained from the limb will lead to the preservation of heart, which will ultimately lead to bio-banking of complex tissues and organs for a myriad of clinical applications relevant to the injured soldiers," says Mehmet Toner, cryobiologist and Professor at Harvard, Mass General and MIT
Stopping Biological Time by Turning Tissue Into a Glassy, Non-Frozen, State
“The process of vitrification, turning the entire ttissueissue directly intointo a glassy state avoiding freezinfreezingg and ice damagedamage,, has opened up aa lot of new possibilities. It's brought us closer to addressingaddressing some of the major barriers to large tissue cryopreservationcryopreservation."." Dr.Dr. Mike Taylor Taylor,, world-leader in vitreousvitreous cryopreservation approacapproacheshes of tissue systems and Adjunct ProfessorProfessor at Carnegie MeMellon.llon.
“While the ability to store living systems for a few years is probably all we need for orgorganan banks to transform transplantation medicine, vitrification should actually enable storage of biological material for literally as long as anyone would ever want. Cryopreservation virtually stops biological time, indefinitelyndefinitely,”,” said Dr. Greg Fahy,Fahy, Chief Science Officer at 21st Century Medicine.
ABOUT THE ORGAN PRESERVATION ALLIANCE. The Organ Preservation Alliance is a non-profit incubatcubateded at SU Labs at NASA Research Park in Silicon Valley,Valley, which is working to catalyze breakthroughs on the remaining obstacles towards the long-term storage of organs by building on recent aadvancesdvances in cryobiologycryobiology and relevant fields. These bbreakthroughsreakthroughs will savesave and enrich the lives of millions; they will also accelerateaccelerate progressprogress towardstowards break-throughs in organ tissue engineering.engineering. InnovInnovationation in these technologies will enable cryobanked, tissue-engineered organs to be available off-the-shelf and on-demand, eventually revolutionizirevolutionizingng human health.
Appendix 1: ContactContact info, titlestitles,, etc, for the world leading trtransplantansplant surgeons andand scientist on our medical and scientific advisory boards that provided quotes above Appendix 2: EnablingEnabling Breakthroughs in TransplantationTransplantation through CryobankingCryobanking – Summary PresentationPresentation
Appendix 1 - Contact Info and Titles to World leading transplant surgeons and scientist
Name Role Title Contactinfo Website DDrr. SeebbaassttiiaanS. GnGiiwwaa CCoo--ffoouunnddeer orof tfthhe OeOrrggaan PnPrreesseerrvvaattiioon AnAlllliiaannccee CCEEOO//PPrreessiiddeenntt, O,Orrggaan PnPrreesseerrvvaattiioon AnAlllliiaannccee ((885577))222222--66666699 http://www.organpreservationalliance.org/betavideo [email protected] Lt Col LuLuisis AlvaAlvarez,rez, PhD Author ofof the DoDDoD CryobaCryobankingnking GGrantrant CallsCalls and ProgramProgram ManagerManager Co-Founding Deputy Director, Defense Tissue Injury & Regen Med [email protected] Program 1 and 2 for them Program 512-699-5281 www.dodsbir.net/solicitation/sbir151/dhp151.htm search for “cryo” to find the right sections Director of Molecular Science and Academy Professor, West Point Program 3: www.dodsbir.net/solicitation/sbi r151/army151.htm Military Academy search for “cryo” to find the right section
Dr. BDr. Bohdohdan Poan Pomahmahacac WorWorld leld leadinading transpnsplanlanttrag surgeoneon;surgt ; led ththe teae teamm that perfperformeormed thed the Director, Plastic Surgery Transplantation Brigham and Women's Hospital http://physiciandirectory.brighamandwomens.org/Details/1250 first full face transplant in United States Medical Director, BWH Burn Center 75 Francis Street, Boston, MA 0211502115 Associa Associatete Professor ssor Profe Phone: (617) 732-7796 Harvard Medical School Fax: (617) 732-6387 Dr. W.P.P.WDr. And. Andrewrew LeLeee WorWorld leald leaderder in transransplaplantt surgerygery;surnt pperf; erformeormedd the nanationtion’s fir’s firstst doubleble--dou Director of the Department of Plastic and Reconstructive Surgery at Phone: 443-287-2001 http://www.hopkinsmedicine.org/profiles/results/directory/profile hand transplant the Johns Hopkins University School of Medicine Appoint Appointmentment Phone:Phone: 443443-997-9-997-9466466 /7041285/wei-ping-lee [email protected]
Dr. Gerald BrandacBrandacherher Was instrumentalinstrumental in designindin esigningg a novel cell-bacell-basedsed immunomimmunomodulatoodulatoryry Scientific Director of the Composite Tissue Allotransplantation Department of Plastic and http://www.hopkinsmedicine.org/transplant/team/team_bios/ger treatment protocol for Vascularized Composite Allotransplantation Program at Johns Hopkins University School of Medicine Reconstructive ald_brandacher.html Surgery, Johns Hopkins (443) 287-6679; [email protected]
D r. Dr. MehMehmetmet ToTonerner Co-fCo-founounderder of the CenCenterter for EngEngineeineerinring ig in Mn Medicedicineine and co-co-AuthAuthoror PPrrooffeessssoorraat tHHaarrvvaarrdd//MMGGH Hannda dMMIITT CCoonnttaaccttIInnffoorrmmaattiioonn https://hst.mit.edu/users/mehmettonerhmsharvardedu of 2014 rat liver 617-724-5336 preservation breakthroughs published in Nature [email protected]
D r. Dr. BoriBoris Rus Rubinbinskysky DiscDiscoveoverrerer of fof fishish antantifreifreezeeze proproteinteins forfos crr cryopyopresreservaervationtion solsolutioutionsns PPrrooffeessssoorraat tUUC CBBeerrkkeelleeyy 66112244EEttcchheevveerrrry yHHaallll, ,MMaaiil lssttoopp11774400 http://www.me.berkeley.edu/faculty/rubinsky/ and innovative University of California, Berkeley isochoric cryopreservation approach Berkeley, CA 94720-1740 [email protected] (510) 725-5845 DrDr. Utk. Utkan DemirmirciciDean CreCreatatoror of iinnonovavativtiven hige high-th-thrhrououghghpuput nant nanololiteiter celr cell manl manipipulaulatiotionn Director of Bio-Acoustic MEMS in Medicine Labs at Partners Research Building https://connects.catalyst.harvard.edu/Profiles/display/Person/4 technologies for Stanford University Renal Division-Rm 267 426 cryopreservation 65 Landsdowne St Cambridge MA 02139 [email protected]
DrDr. GregegororyGr. Fay Fahyhy LeLeadad scscienientistist bet behihind thetnd he firfirst sucucsst cecessssfuful trl trananspsplalant ont of af a ChChieieff ScScieiencncee OfOffificecerr at 2 121stst CeCentntururyy MeMedidicicinene 2 121stst CeCentntururyy MeMedidicicinene,, FoFontntanana,a , CACA http://www.21cm.com/contact.html cryopreserved and vitrified [email protected] mammalian organ (rabbit kidney) Toll Free in the U.S.: (866) 889-1215 Outside the U.S.: (909) 466-8633 FAX: (909)-466-8618
Dr. KeKelvin BrocrockbakbanknkBlvin InvInventoentorr ooff clinicaicalclin cryol cryoprespreservervatioationn methmethodsods currerrentlycu ently emplmployeoyed ford for President and Chief Science Officer of Cell & Tissue Email [email protected] http://www.clemson.edu/ces/bioe/faculty- viable meniscal Systems Phone 843-514-6164 staff/directory/brockbank.html allografts, allogeneic heart valves, ligaments, and vascular grafts DrDr. ErikE. rik WoWoododss DevDevelelopopeded enenhahancnceded metmethohodsds fofor tr thehe prpreseserervavatiotion andan nd babanknkining og off President of the International Society of Cryobiology and [email protected] http://www.cookgbt.com/?page=contact umbilical cord CEO of Cook General BioTechnology and Genesis Bank Phone: 800.265.0945 blood-derived stem cells Fax: 317.917.3444
D rDr.. JJaaccoobb LLaavveeee LLeeaaddiinngg hheeaarrtt ssuurrggeeoonn Director of Heart Transplantation, Sheba Medical Center E-mail - [email protected] http://eng.sheba.co.il/Sheba_Hospitals/Acute_Care_H http://eng.sheba.co.il/Sheba_Hospitals/Acute_Care_Hospital/Dospital/D Implanted the first left Ventricular Assist Device in Israel President of the Israel Society of Transplantation. ivision_of_Surgery/Cardiac/Heart_Transplantation/
patientsNational authority in the management of terminally ill heart failure Associat AssociateMedicinee of ProfessorProfes the Telsor Aviv of SurgeryS Universityurgery at the FacultyFaculty oof f Dr. PDr. Pasqasqualuale PatrizioizioPatre LeaLeadinding cling cliniciaician in Inn Infertfertilitility. SpecpecialiialistSy. st in WholholeW ovae ovaryry Director of the Yale Fertility Program Appt(20 Appt(203)3) 785-47084708785- http://medicine.yale.edu/obgyn/people/pasquale_patrizio.profile cryopreservation, Oocyte Professor of obstetrics, gynecology & reproductive sciences at the Office(203) 764-5866 freezing, Genetics of oocytes and cumulus cells YaleYale [email protected] School of Medicine
DrDr. MikikeM. TayaylolorrTe WoWorldrld-le-leadadeerr in vivitretreouous cs cryryopoprereseservarvatiotion an apppproroacachehes os of tf tisissusuee Adjunct ProfessorProfessor at CarnegieCarnegie MMellonellon andand VP foforr R&D, Cell & TissueeTissu Email: [email protected] http://www.cmu.edu/me/people/taylor.html http://www.cmu.edu/me/people/taylor.html systems Systems
t f a r d
ENABLING BREAKTHROUGHS IN ORGAN TRANSPLANT MEDICINE
Maria Bill Lee Mary
THEY WERE SOME OF THE LUCKY ONES
Millions of others are waiting for a new organ worldwide. Many will die before receiving one
WE WANT TO CHANGE THAT WITH YOUR HELP
2
AN INTERDISCIPLINARY TEAM ENABLING BREAKTHROUGHS AN OFINTERDISCIPLINARY DOCTORS, SCIENTISTS, TEAM INENABLING THE LONG-TERM BREAKTHROUG PRESER-HS POLICY INFLUENCERS, VATION OF ORGANS TO COMMUNICATORS & SAVE MILLIONS ENTREPRENEURS OF LIVES
NASA Research ParkEligible | Building to receive 20, S.tax Akron deductible Road donations| Moffett Fieldvia 50 | CA1(c)(3) 94035 scal | OrganPreservationAlliancsponsorship e.org
3
IN PARTNERSHIP INCUBATED AT SU LABS AT NASA WITH RESEARCH PARK IN SILICON VALLEY
prizes & partnerships to advance using accelerating technologies the regeneration, preservation to address humanity’s biggest and engineering of organs challenges
4
ACCELERATING THE DEVELOPMENT OF ACCELERATING THE DEVELOPMENT OF REVERSIBLE LONG-TERM HUMAN ORGAN STORAGE
TO CATALYZE A VITAL NEW INDUSTRY THAT
PERFECTPROCESS,S THE SAVING ORGAN AND PRES ENRICHINGERVATION MILLIONS OF LIVES
5
BREAKTHROUGHS IN ORGAN TRANSPLANTATION OVER THE LAST 2-3 DECADES SAVE LIVES EVERY HOUR
“Kidney transplants seem so routine now. But the rst one was like Lindbergh’s ight across the ocean.” Dr. Joseph E. Murray, Nobel Prize recipient and surgeon for rst successful kidney transplant 6
ELLEN, AGE 38 is dying of organ failure; she may or may not receive an organ in time
Note: All case studies shown are illustrative examples and do not represent real persons. 7
SHORTAGETHE GROWING
Waiting List 120,873
Transplants Donors
28,052 17, 917 13, 140 5,927 14,013
2012
THE U.S. ORGAN WAIT LIST HAS GROWN RAPIDLY, WHILE THE NUMBER OF ORGAN DONORS HAS STAGNATED
Source: OPTN/SRTR 2012 Annual Report and website data 8
TRUE NEED COULD BE 10X LARGER THAN OFFICIAL WAITING LIST SUGGESTS
Annual transplants 28,000
Total waiting list 120,000
Annual deaths prevent- 900,000 able by transplantation
0 200,000 400,000 600,000 800,000 1,000,000
AN ESTIMATED 35% OF ALL U.S. DEATHS COULD BE PREVENTED OR SIGNIFICANTLY DELAYED BY ORGAN TRANSPLANTATION
Source: Human Organ Project; OPTN/SRTR 2012 Annual Report and website data; Fahy, Wowk, and Wu, “Cryopreservation of Complex Systems,” Rejuvenation Research V9,II 2006; National Vital Statistics Report. Lanza, West, Atala, et al, “Generation of Histocompatible Tissues Using Nuclear Transplantation”, Nature Biotechnol. 2002, and Lanza, et al., “ The ethical reasons for stem cell research”, Science 293, 1299 (2001) 9
EVEN FOR THOSE FORTUNATE ENOUGH TO RECEIVE COMPATIBLE ORGAN TRANSPLANTS IN TIME, SERIOUS CHALLENGES REMAIN
VITALITY LONGEVITY COST
Immunosuppressants that keep Transplanted organs often don’t Immunosuppression treatment, which your body from rejecting an organ last long. You need a new one must be administered for the duration of can harm your immune system, every 5-15 years, forcing you to patients lifetime, can cost hundreds of raising the odds of severe illness endure the waiting list each time thousands of dollars for a single person
1 http://kidney.niddkhttp://kidney.niddk.nih.gov/.nih.gov/ 2 Lanza, West, Atala, et al, “Generation of HistocompHistocompatibleatible TissuesTissues Using Nuclear Transplantation”, Nature Biotechnol 10
SEMU, AGE 14, KENYA Due to logistical challenges, no attempt will be made to nd an organ for Semu. In other parts of the world, the life-saving transplant operation he needs is done routinely
11
GLOBALLY GLOBALLY THE PROBLEM IS EVEN MORE SEVERE THAN IN THE US
number of organs transplanted per mln population
0-2,4
2,5-9
10-24
25-49
50-74
> 75
unknown/ not applicable
ACCORDING TO THE WORLD HEALTH ORGANIZATION, ORGAN TRANSPLANTS ARE CURRENTLY MEETING LESS THAN 10% OF THE GLOBAL NEED
Source: World Heath Organization and Global Observatory on Donation and Transplantation (http://www.transplant-observatory.org/) 12
SONIA AGE 15 UK MARK AGE32 US SONIA, AGE 15, UK MARK, AGE 32, US has cancer that is curable, but her ovaries will be lost both his arms while on duty damaged by the required chemotherapy. She will for the military and would like never have children and will suer health issues nothing more than to receive related to hormone imbalances successful arm transplants 13
A COMMON NEED
14
THE REVERSIBLE AND EFFICIENT BANKING OF LARGE TISSUE SYSTEMS WOULD SAVE MILLIONS OF LIVES AND RADICALLY IMPROVE MILLIONS OF OTHERS
15
A POWERFUL SOLUTION
WHAT IF ORGANS COULD BE RELIABLY PRESERVED, FOR WHEN THEY ARE NEEDED?
BETTER FEWER LESS IMMUNO- MORE MATCHES REJECTIONS1 SUPPRESSION1 ORGANS2
LOWER LESS DISEASE MORE LIVES SAVED BETTER PROTECTION COSTS3 TRANSMISSION IN EMERGENCIES4 OF FERTILITY5
1 Long-term organ preservation would provide time to train a recipient’s immune system - leading to both organ rejection and the need for immunosuppressants potentially falling to zero as the promising work on immunologic toler- ance induction is perfected. 2 Ability to bank organs will enable use of more organs and based on the better matches and fewer rejections lead to less loss of organs. In time, limbs and appendages can probably be preserved by similar methods used for vital organs. 3 Treatment for kidney decease costs $43 billion a year in the US and the aggregate cost has been estimated at more than $1 trillion during a decade (kidney.niddk.nih.gov and Lanza, West, Atala, et al, “Generation of Histocompatible Tissues Using Nuclear Transplantation”, Nature Biotechnol) 4 Banked organs could make it possible to save policemen, re-ghters and civilians in accidents who urgently need an organ within hours to save their life; long-term preservation would also allow for an inventory of limbs and organs for use in war-related injuries. 5 Concept has been demonstrated using ovarian tissue in humans and full ovaries in other mammals. 16
MANY MORE ORGANS
% OF UNHARVESTED ORGANS FROM DECEASED DONORS
if half of the wasted hearts and lungs 100% could be used, the U.S. waitlist for could be used, the U.S. waitlist for these organs would be extinguished in about 2- 3 years 80%
60%
40%
20%
0% INTESTINE HEART PANCREAS LUNG LIVER KIDNEY Equivalent Procurement $586M $452M $323M $305M $95M $78M Cost
PROCUREMENT COSTS ALONE OF THOSE ORGANS WOULD CONTRIBUTE A MULTI-BILION DOLLAR MARKET
Source: Based on 2012 numbers from US Dept. of Health and Human Services. 17
IMAGINE A FUTURE IN WHICH TISSUE ENGINEERING OF ORGANS IS ROUTINE Sheila, 68, would be able to maintain “backup copies” of each of her organs, prolonging her health and potentially saving her life
18
COMBINING ORGAN MANUFACTURING & BANKING
THE ABILITY TO REPLACE VITAL ORGANS ON DEMAND IS ESTIMATED TO SIGNIFICANTLY DECREASE HUMAN MORTALITY
COMBINED, TISSUE ENGINEERING AND Hypothetical 100100 2020 e e v v with major organ ORGAN BANKING CAN POTENTIALLY: l l i i A A replacement g g i i n n 8080 t t l l n n n n a a i i e e v v • a a s s i i DELAY MORE THAN 30% OF DEATHS Present e e v v m m r r r r e e P P u u R R / / S S n n 6060 l l f f o o a a o o i i 1010 c c • t t i i d d INCREASE THE LIKELIHOOD OF LIV- a a t t o o l l e e o o u u h h t t h h p p l l i i ING TO 80 BY 2 TIMES o o 4040 o o e e P P p p k k f f y y i i o o H H L L t t Hypothetical/ n n e e Present (right axis) • c c 2020 INCREASE LIKELIHOOD OF LIVING P P e e r r TO 90 BY 10-20 TIMES 22 00
00 2200 4400 6600 8800
Age (Years)
Source: Fahy, Wowk, and Wu, “Cryopreserva“Cryopreservationtion of ComplexComplex Systems,” Rejuvenation Research V9,V9,IIII 2006; NationalNational Vital Statistics Report. Lanza, West,West, Atala, et al, “Generation of Histocompatible Tissues Using Nuclear Transplantationation”,”, Nature Biotechnol. 2002, and Lanza, et al., “The ethical reasons for stem cell research”, ScienSciencece 293, 1299 (2001) 19
THE ABILITY TO BANK ORGANS WOULD ACCELERATE THE DE- VELOPMENT OF TISSUE ENGINEERING TECHNOLOGIES
INCREASED GREATER INCREASED DEMAND IMPACT FUNDING
Ecient ways to store and The ability to generate backup Increased future demand and manage backup organs would organs would save more lives greater impact should generate likely increase demand for if coupled with the commen- increased interest and funding, likely increase demand for if coupled with the commen increased interest and funding, tissue engineered organs by surate ability to store them so thereby accelerating the pace several orders of magnitude1 they are on demand in times of of tissue engineering urgent need2 breakthroughs
could1 The demandhave a unqiue, for tissue-engineered compatible set organsof backup could organ thens basedincrease on dramatically his or her unique as the DNA. reliable The banking demand of for organs tissue-engineered becomes possible. organs At could the extreme,increase fromonce aroundthese technologies 30-50,000 are a readilyyear to availableas much as in 1.8 the bnUS, initially every American (300 mn * 6 organs) and 18 mn a year after that (3 mn newborns annually * 6 organs). And that’s just the US. 2 Organs banks will increase the survival rate dramatically for individuals requiring a transplant urgently — whether within a few weeks with just hours. This could help any of us, and is particularly important for the policemen, remen and soldiers who serve us, as well as those with pre-existing medical conditions. 20
AND YET...
OVER THE LAST 30 YEARS VERY LIMITED FUNDING AND RESEARCH HAVE GONE TOWARD SOLVING THE LONG-TERM ORGAN PRESERVATION PROBLEM
21
LONG-TERM ORGAN BANKING IS ACHIEVABLE
Stem cells, sperm, eggs, and embryos have been routinely cryopreserved for long-term banking in a reversible fashion for decades Breakthroughs in ice blockers, cryoprotectants and vitrication have made it possible to preserve arteries, veins, heart valves, tracheas, cartilage, corneas, organ slices and more in recent years
Feasibility demonstrated by progress with rat hearts, pig and rodent livers, sheep ovaries and pig uteri, for instance, as well as in the ground- breaking cryopreservation and successful transplantation of a rabbit kidney
Sources: Gavish, Z., et al,. 2008. “Cryopreservation of whole murine and porcine livers”, Rejuvenation Res, 11, 765-72, Armitage WJ, Pegg DE., “The contribution of the cryoprotectant to total injury in rabbit hearts frozen with ethylene glycol”, Cryobiology. 1979, G. Amir et al., “Improved viability and reduced apoptosis in sub-zero 21-hour preservation of transplanted rat hearts using anti-freeze proteins,” J Heart Lung Transplant, 24:1915-29, 2005., G. Fahy et al, ”Physical and biological aspects of renal vitrication “, Organogenesis. 2009 Jul-Sep; 5(3): 167–175 and Xu H, et al, “An experimental research on cryopreserving rabbit trachea by vitrication”, Cryobiology. 2009, Arav A., et. al, Oocyte recovery, embryo development and ovarian function after cryopreservation and transplantation of whole sheep ovary.Hum Reprod. 2005 Dec;20(12):3554-9. Epub 2005 Sep 20. 22
A TALE OF TWO KIDNEYS
-140°C
STRAIGHT VITRIFIED FROZEN
Source: 21st Century Medicine 23
GROUND-BREAKING, SUCCESSFUL TRANSPLANT OF CRYOPRESERVED RABBIT KIDNEY published by Dr Gregory M Fahy, Dr Brian Wowk, et al, at 21st Century Medicine in 2009
STARTING FROM A LOW BASE, UNDERSTANDING OF CRYOPRESERVATION HAS IMPROVED SIGNIFICANTLY
PUBLICATIONS MENTIONING PUBLICATIONS MENTIONING “CRYOPRESERVATION” “VITRIFICATION”
1600 250
s 1400 s l e l e i c i c r t r t 200 a 1200 a d d e e M M b b P u 1000 P u 150 l l a a u 800 u n n n n A A f f 100 o 600 o r r e e b b m 400 m u u N N 50 200
0 0 0 4 8 9 2 9 6 0 4 8 1 2 0 4 8 9 2 9 6 0 4 8 1 2 9 8 9 8 9 8 9 9 0 0 0 0 9 8 9 8 9 8 9 9 0 0 0 0 1 1 1 1 1 2 0 2 0 2 0 2 1 1 1 1 1 2 0 2 0 2 0 2 25
SCIENTISTS WITH RELEVANT CRYOBIOLOGY EXPERTISE EXIST AROUND THE WORLD
Examples: Berkley, Carnegie Mellon, Harvard, University of Tennessee, MIT, University of Minnesota Villanova University, Arizona State ACADEMIC University, US Department of Agriculture’s ARS INSTITUTIONS Laboratory and St. Luke’s Hospital (St Louis)
Examples: Cell & Tissue Systems, 21st Century Medicine, Cook General BioTechnology and Innovative Biological Preservation Technologies PRIVATE SECTOR Corporation LABS
Examples: University of Liverpool, University College London, Fertilesafe (Core Dynamics) - Advanced Cryopreservation Technologies, INTERNATIONAL University of Seville, University of Groningen, and the UNESCO Chair in Cryobiology
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THE CHALLENGE CAN BE BROKEN DOWN INTO A FEW SOLVABLE “ENGINEERING PROBLEMS”
1. EXCESSIVE ICE 2. ABOVE THRESHOLD 3. TOO EXTREME FORMATION LEVEL OF MECHANICAL / A. TOO MUCH ICE NUCLEATION CRYOPROTECTANT THERMO DYNAMIC B. TOO RAPID ICE GROWTH/ TOXICITY STRESS CRYSTALLIZATION (DURING COOL-DOWN, BUT PRIMARILY COOL DOWN, BUT PRIMARILY DURING REWARMING)
4. POTENTIAL FOR TOO MUCH CHILLING INJURY
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TOOLS AND UNDERSTANDING FROM OTHER RAPIDLY ACCELERATING DOMAINS COULD HELP CREATE NEEDED BREAKTHROUGHS
Metabolomics, Proteomics and Genomics
to better understandshock and and fi ndtoxic ways reactions to interve to cryoprotectantsne with chilling injury, osmotic High throughput screening and computational and conceptual chemistry and methods to discover more effective cryoprotectant cocktails Gas persuf flaton to accelerate cooling, warming and avoid fracturing
Mechanical engineering and material science to better re-understand and avoid fracturing
Civilian and military trauma and resuscitation medicine and hypothermic surgery to minimize ischemic injury and optimize revival Stem cell science, regenerative medicine and expertise in key metabolites, enzymes and certain amino acids to prepare and harden cells ahead of potential damage and optimize healing of any that occurs
And many other domains such as Biochemistry, Molecular Biology, Electron Microscopy and Scanning Sciences, Automation and General Engineering and Surgeon Skill
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