Table Of ContentAdvances in Experimental Medicine and Biology 1247
Cell Biology and Translational Medicine
Kursad Turksen Editor
Cell Biology and
Translational
Medicine,
Volume 8
Stem Cells in Regenerative Medicine
Advances in Experimental Medicine
and Biology
Cell Biology and Translational Medicine
Volume 1247
SubseriesEditor
KursadTurksen
Moreinformationaboutthissubseriesathttp://www.springer.com/series/15838
Kursad Turksen
Editor
Cell Biology and
Translational Medicine,
Volume 8
Stem Cells in Regenerative Medicine
Editor
KursadTurksen(Retired)
OttawaHospitalResearchInstitute
Ottawa,ON,Canada
ISSN0065-2598 ISSN2214-8019 (electronic)
AdvancesinExperimentalMedicineandBiology
ISSN2522-090X ISSN2522-0918 (electronic)
CellBiologyandTranslationalMedicine
ISBN978-3-030-45892-8 ISBN978-3-030-45893-5 (eBook)
https://doi.org/10.1007/978-3-030-45893-5
#SpringerNatureSwitzerlandAG2020
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Preface
InthisnextvolumeintheCellBiologyandTranslationalMedicineseries,we
continuetoexplorethepotentialutilityofstemcellsinregenerativemedicine.
Chapters in this volume cover advances and challenges in applications of
particular stem cell populations in a variety of diseases and conditions, and
certaingovernanceandpolicyissuesandoptions.
I remain very grateful to Gonzalo Cordova, the Associate Editor of the
seriesandacknowledgehiscontinuoussupport.
I would also like to acknowledge and thank Sara Germans-Huisman,
Assistant Editor, for her outstanding efforts in helping to get this volume to
theproductionstages.
A special thank you goes to Rathika Ramkumar and Anand
Venkatachalam fortheiroutstandingeffortsintheproductionofthisvolume.
Finally,sincerethankstothecontributorsnotonlyfortheirsupportofthe
series, but also for their insight and effort to capture both the advances and
remaining obstacles in their areas of research. I trust readers will find their
contributionsasinterestingandhelpfulasIhave.
Ottawa,ON,Canada KursadTurksen
v
Contents
TheFutureofStemCellResearchanditsClinicalTranslation
inCanada:ExploringQuestionsofGovernanceandPolicy
Options. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
AmyZarzeczny
FutureCellandGeneTherapyforOsteoarthritis(OA):
PotentialforUsingMammalianProteinProductionPlatforms,
IrradiatedandTransfectedProteinPackagingCellLinesfor
Over-ProductionofTherapeuticProteinsandGrowthFactors. . . 17
AliMobasheri
TheHorizonofGeneTherapyinModernMedicine:Advances
andChallenges. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
BabakArjmand,BagherLarijani,MotaharehSheikhHosseini,
MoloudPayab,KambizGilany,ParisaGoodarzi,
PeyvandParhizkarRoudsari,MobinaAmanollahiBaharvand,
andNeginsadatHoseiniMohammadi
DevelopmentsinArtificialPlateletandErythroidTransfusion
Products. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
NeslihanMeric,GulenGuneyEsken,MerveUslu,
andFatihKocabas
AdvancingMesenchymalStemCellTherapywith
CRISPR/Cas9forClinicalTrialStudies. . . . . . . . . . . . . . . . . . . . 89
AliGolchin,ForoughShams,andFarshidKarami
MesenchymalStemCellsinAsthma. . . . . . . . . . . . . . . . . . . . . . . 101
TuncAkkoc
OocyteAging:TheRoleofCellularandEnvironmentalFactors
andImpactonFemaleFertility. . . . . . . . . . . . . . . . . . . . . . . . . . . 109
TokaA.Ahmed,SaraM.Ahmed,ZaynabEl-Gammal,
ShaimaaShouman,AshrakatAhmed,RagaaMansour,
andNagwaEl-Badri
vii
viii Contents
TargetingCancerMetabolismandCellCyclebyPlant-Derived
Compounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
EsraAydemirÇoban,DidemTecimel,FikrettinŞahin,
andAyşenAsl{H{zl{Deniz
DifferentiationPotentialofMesenchymalStemCellsinto
Pancreaticβ-Cells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
SafaAydin,DeryaSağraç,andFikrettinŞahin
ZoominginacrosstheSkin:AMacro-to-MolecularPanorama. . . 157
AyşenAslıHızlıDeniz,EzgiAvşarAbdik,HüseyinAbdik,
SafaAydın,FikrettinŞahin,andPakizeNeslihanTaşlı
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
AdvExpMedBiol-CellBiologyandTranslationalMedicine(2020)8:1–16
https://doi.org/10.1007/5584_2019_450
#SpringerNatureSwitzerlandAG2019
Publishedonline:21November2019
The Future of Stem Cell Research and its
Clinical Translation in Canada: Exploring
Questions of Governance and Policy
Options
Amy Zarzeczny
Abstract context is particularly timely at present given
theemergingdomesticprivatemarketforstem
Stem cell research is a promising area of bio-
cell-basedinterventionscoupledwithscientific
medicalresearchwithtremendouspotentialfor
developments in the field that are highlighting
increasing our understanding of human devel-
ambiguities and other challengeswith ourcur-
opment and for improving clinical treatment
rentregulatoryframework.
options across a range of serious conditions.
However,ithashistoricallyalsobeenacomplex
Keywords
field, both scientifically and ethically. It raises
numerous policy tensions including those Stemcell·Policy·Ethics·Regulation·
relatedtotheacceptabilityofdifferentformsof Governance·Unproveninterventions
researchinthefieldand,morerecently,regard-
inghowtorespondtotherapidlygrowingpri-
vate market for clinical applications that lack 1 Introduction
broadly accepted forms of evidence of safety
and efficacy. Using the Canadian market for Regulating fast moving fields of science, like
unproven stem cell interventions as a case stem cell research, is no simple feat. One chal-
study,thisreviewpaper identifiesquestions of lengepolicymakersfaceisthatitcanbedifficult
governanceandpolicyoptionsastheyrelateto to predict with any accuracy both the potential
the future of stem cell research and its clinical benefits and also the potential risks of new
translation in Canada. Key areas of inquiry technologies and avenues of research (Butenko
include the roles and influence of evidence, and Larouche 2015; Harmon et al. 2013). How-
scientific and clinical imperatives, and public ever,understandingbenefitsandrisksiscritically
pressure on policy decisions, as well as the important when it comes to trying to balance
roleofregulationinmanagingrisksanduncer- diverse and sometimes competing policy
tainty in fast moving fields of biomedicine. priorities. For example, in the stem cell field
Examining these questions in a Canadian (as is true in others), there are a number of both
pushes and pulls relevant to policy choices
including, though certainly not limited to, the
A.Zarzeczny(*) desiretostimulateeconomicgrowth,createjobs,
JohnsonShoyamaGraduateSchoolofPublicPolicy,
encourage biomedical developments likely to
UniversityofRegina,Regina,Canada
improve clinical treatment options, respond to
e-mail:[email protected]
1
2 A.Zarzeczny
pressure from the public, patients or other stake- 2 Stem Cells: Promises, Pitfalls
holder groups, address ethical, moral, and/or and Policy Challenges
otherconcerns,andberesponsivetointernational
pressures.Althoughnotalwaysclearlydelineated 2.1 Context – Regulation
or directly acknowledged, it is important to be and Governance of Stem Cell
cognizant of these various potential influences Research in Canada
on decision-making with respect to science and
innovation policy (Phillips and Schmeiser 2017) Stemcellresearchisapromisingareaofbiomed-
–includinginthecontextofstemcellresearch– ical research with tremendous potential for
whenidentifyingandconsideringpolicyoptions. increasing our understanding of human develop-
Itcanalsobedifficultforregulatorstoidentify mentandforimprovingclinicaltreatmentoptions
whattoolsorstrategiesarethebestfitforagiven acrossarange ofseriousconditions.However,it
area or issue in order to achieve their desired has historically also been a complex field, both
objectives while limiting negative or unintended scientifically and ethically. It raises numerous
effects.Inmanycases,hardlawapproachessuch policy tensions including those related to differ-
as criminalization are ill-suited to regulate fields ent avenues of stem cell research. For example,
thatarechangingquickly.Theirinflexiblenature early debates about the acceptability – or lack
can make it difficult to adapt to unanticipated thereof–ofresearchinvolvingthedestructionof
developments intheregulated field,risking legal human embryos and concerns about different
ambiguityand/orunintendedconsequenceswhen kinds of applications such as reproductive clon-
thelawdoesnotkeeppacewithscientificrealities ing,shapedmuchoftheearlypolicydiscoursein
(Ogbogu et al. 2018b). Legal authority is also the field and featured prominently in public
generally restricted by jurisdiction. Indeed, lim- forums including the media (Caulfield et al.
ited jurisdictional reach for regulators is a grow- 2010) and Canadian parliamentary debates
ingconcern,particularlywhenconsideringissues (CaulfieldandBubela2007).
withinternationalimplicationsthatincludecross- Inmanyways,thecurrentgovernanceofstem
border and internet-based activities, such as cellresearchinCanadaisaproductofthoseearly
marketsforstemcell-basedinterventions(Shalev debates, with a long history of controversy. It is
2010;Sippetal.2017). beyond the scope of this paper to provide a ful-
In this review paper, I will identify questions some account of that history here (see Cattapan
ofgovernanceandpolicyoptionsastheyrelateto and Snow 2017). The work of the Royal Com-
the future of stem cell research and its clinical mission on New Reproductive Technologies,
translation in Canada, using the market for established in 1989, was particularly influential.
unprovenstemcellinterventionsasacasestudy. Its1993report,ProceedwithCare–FinalReport
Tosetthestageforthisdiscussion,Iwillbeginby of the Royal Commission on New Reproductive
framing the relevant regulatory context and by Technologies(Baird1993),calledfortheregula-
introducing what I suggest are governance tionofawiderangeofactivitiesrelatedtorepro-
challenges in this space, drawing on current ductive technologies, including research using
examples from the field of stem cell research to human embryos. This report was followed by a
highlight specific issues. I will then use the mar- numberoffailedlegislativeinitiatives,ultimately
ketforunprovenstemcellinterventionsasacase leading to the passing of the Assisted Human
study to illustrate these governance challenges, Reproduction Act (S.C. 2004, c. 2) (AHRA) in
and to serve as a foundation for an exploration 2004. The AHRA was federal legislation that
offuturestrategies.Thepaperwillconcludewith purported to govern aspects of reproductive
a brief discussion of policy options and gover- technologies as well as particular avenues of
nance strategies, with a view to contributing to research. It did so by way of creating two
futureresearchstrategiesinthisarea. categories of activities – those that were
