The Origin of a New Progenitor Stem Cell Group in Human Development: An Immunohistochemical-, Light- and Electronmicroscopical Analysis

90 Pages·2019·7.966 MB·English

by  Hubert Wartenberg, Andreas Miething, Kjeld Møllgård

Advances in Anatomy, Embryology and Cell Biology
Hubert Wartenberg
Andreas Miething
Kjeld Møllgård
The Origin of a
New Progenitor
Stem Cell Group
in Human
Development
An Immunohistochemical-, Light- and
Electronmicroscopical Analysis
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UniversidadAutónomadeMadrid,Ave.ArzobispoMorcillos/n,28029Madrid,Spain
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2610Wilrijk,Belgium
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Advances in Anatomy,
Embryology
and Cell Biology
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Hubert Wartenberg Andreas Miething
Kjeld Møllgård
The Origin of a New
Progenitor Stem Cell Group
in Human Development
An Immunohistochemical-, Light- and
Electronmicroscopical Analysis
HubertWartenberg AndreasMiething
DepartmentofAnatomy DepartmentofNeuroanatomy
andCellBiology InstituteofAnatomy,UniversityofBonn
InstituteofAnatomy Bonn,Germany
UniversityofBonn
Bonn,Germany
KjeldMøllgård
DepartmentofCellularandMolecular
Medicine
UniversityofCopenhagen
KøbenhavnN,Denmark
ISSN0301-5556 ISSN2192-7065 (electronic)
AdvancesinAnatomy,EmbryologyandCellBiology
ISBN978-3-030-02049-1 ISBN978-3-030-02050-7 (eBook)
https://doi.org/10.1007/978-3-030-02050-7
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Preface
Since studies on human stem cells are legally restricted in Germany (Wiedemann
et al. 2004), the use of the stem cells in this study needs some introductory
explanations. The applied human embryos and fetal tissues have been obtained in
the years 1968 (Vossmeyer 1971 and Holstein et al. 1971) and 1985 (Wartenberg
1985,1989a,b):wegotthemfromlegalinterruptionsinlocalhospitalsinHamburg
and in the University Hospital Bonn, Germany. The material was taken from male
and female embryos and fetuses ranging from 21 to140 mm crown-rump length
(CRL).Theyderivedfrommedicalabortionswhichwereprovidedforpathological
examinations. In each case, the consent of the heads of the clinical institution
(in Bonn: Prof. Dr. Krebs, head of the Gynaecologic Clinic, University of Bonn,
Germany) and that of the physicians who performed the medical treatment were
obtained.Whenthepresentstudiesonstemcellswerestarted,theembeddedtissues
couldstillbeusedandgaveexcellentresultsevenafterseveraldecadesofstorage.In
all cases, the stem cells have been obtained long before the current legislation
restricted thestudies on human stem cells. The restrictions presented inthe Delphi
studyalreadymentioned(Wiedemannetal.2004)weremerelyretrospective.What-
everthelegalobligationsareabouttheuseofhumanstemcells,theresultspresented
here offer a very important view on stem cell biology. The human embryonic and
fetal material used for Chromogranin A-immunohistochemistry was based on the
specimens already described (Møllgård et al. 2010 and Mamsen et al. 2012). In
short, they were obtained in connection with legal abortions carried out in Copen-
hagen,Denmark.Oralandwritteninformationwasgivenandinformedconsentwas
obtainedfrom all contributing women, accordingto andapproved by theRegional
CommitteeonBiomedicalResearchEthicsCopenhagenandFrederiksbergCounties
(KF(01)258206).
Bonn,Germany HubertWartenberg
Bonn,Germany AndreasMiething
KøbenhavnN,Denmark KjeldMøllgård
v
vi Preface
References
Holstein,A.F.,Wartenberg,H.,Vossmeyer,J.:ZurCytologiederpränatalenGonadenentwicklung
beimMenschen.III.DieEntwicklungderLeydigzellenimHodenvonEmbryonenundFeten.Z.
AnatEmtwickl-Gesch.135,43–68(1971)
Mamsen, L.S., Brøchner, C.B., Byskov, A.G., Møllgard, K.: The migration and loss of human
primordialstemcellsfromthehindgutepitheliumtowardsthegenitalridge.IntJDevBiol.56,
771–778(2012)
Møllgård, K., Jespersen, A., Lutterodt, M.C., Yding Andersen, C., Høyer, P.E., Byskov, A.G.:
HumanprimordialgermcellsmigratealongnervefibersandSchwanncellsfromthedorsalhind
gutmesenterytothegonadalridge.MolHumReprod.16,621–631(2010)
Vossmeyer, J.: Zur Cytologie der praenatalen Gonadenentwicklung beim Menschen. I. Die
Histogenese des Hodens, an Eponschnitten untersucht. Z. Anat. Entwickl.-Geschichte. 134,
146–164(1971)
Wartenberg,H.:Morphologicalstudiesontheroleoftheperiductalstromaintheregressionofthe
humanmaleMüllerianduct.AnatEmbryol.171,311–323(1985)
Wartenberg,H.:DifferentiationandDevelopmentofthetestes.In.TheTestis,SecondEdition,edit.
byH.BurgerandD.deKretser,RavenPress,NewYork(1989a).
Wartenberg,H.:Ultrastructureoffetalovaryincludingoogenesis.In:Blerkom,V.,Motta,J.(eds.)
Ultrastructureofhumangametogenesisandearlyembryogenesis:Chapter3,pp.61–84(1989b)
Wiedemann, P.M., Simon, J., Schicktanz, S., Tannert, C.: The future of them cell research in
Germany.ADelphiStudy.EMBOreports.5,927–931(2004)
Acknowledgement
TheexcellenttechnicalassistanceofMrs.U.Schwaabisgratefullyacknowledged.
vii
Abstract
In light and electron microscopic sections of plastic-embedded human embryonal
andfetalorgans,theoriginofanewgroupofprogenitorstemcellshasbeenfound
whicharedealtwithinthepresentstudies.Thedistributionofthesecellscanresultin
a large quantity of ectopic stem cells. The observation of these ectopic stem cells
leads us to postulate the existence of a basic wave of stem cell progenitors. This
processproceedsearlierandindependentlyfromgermcellmigration.Thisfirstwave
of progenitor stem cell migration initially reaches the peri-aortal AMG region
(Aortal-Mesonephric-Gonadal region). From here, some of these progenitor cells
entertheaorta,aredistributedthroughthevascularsystem,andbecometheembry-
onal stem cells (reserve cells) in many peripheral tissues. A second part delivers
progenitorcellsfortheadrenal“anlage.”WithintheperipheralZonadefinitivaofthe
adrenal cortex, the progenitor cells multiply and subsequently leave the adrenal
cortex through a gate of the capsule. The progenitor cells arrive at the pre-aortal
sympathetic plexus (“second brain”). Within the plexus ganglia they form new
organ-likeclusters,theparaganglia.Inasecondprocess,theprogenitorcells(chro-
maffin cells) enter sympathetic nerve bundles. Here an “axonal migration” starts,
whichguidestheprogenitorcellstoseveralperipheralorgans.Duringthismigration
process, the stem cells develop into their final state. In the adrenal cortex, the
ingrowing nerves guide the stem cells to the adrenal medulla. In the pancreas, the
ingrowingnervefibersguidethestemcellstotheislets.
Keywords Human(cid:1)Progenitorstemcells(cid:1)AMGregion(cid:1)Adrenal(cid:1)Zonadefinitiva
(cid:1) Para-aortal plexus (cid:1) Paraganglia (cid:1) Autonomic nervous system (cid:1) Guided axonal
migration (cid:1) Pancreas (cid:1) Gonadal and Intestine stem cells (cid:1) Stem cells II (cid:1) APUD
system(cid:1)Teratoma
ix
Contents
1 TheOriginofaNewProgenitorStemCellGroupinHuman
Development. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 DistributionofProgenitorStemCellsfromtheAMG-Systemandthe
Adrenal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1.1 Introduction.. . . .. . . .. . . .. . . .. . . .. . . . .. . . .. . . .. . 1
1.1.2 MaterialsandMethods. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.2 DevelopmentoftheAdrenalMedullaandOtherEndocrine
Glands. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
1.2.1 DevelopmentoftheAutonomicInnervationoftheAdrenal
GlandandtheFormationoftheAdrenalMedulla. . . . . . . . . 34
1.2.2 DevelopmentoftheAutonomicInnervationoftheHuman
PancreasandOriginofthePancreaticIslets. . . . . . . . . . . . . 37
1.2.3 DevelopmentoftheHumanParathyroidGland. . . . . . . . . . 44
1.2.4 FetalStemCellsatPerigonadalandIntragonadalSites. . . . . 46
1.2.5 Down-GrowthofAutonomicNervesintheStomachandthe
IntestineTube:TheMigrationandtheWhereaboutsofthe
StemCells. . .. . . . .. . . .. . . . .. . . .. . . .. . . . .. . . .. . . 51
1.2.6 Discussion:TheProcessofStemCellDistributionand
MigrationWithintheAutonomicNervestoOrgansofthe
HumanDevelopingOrganism. . . . . .. . . . . . .. . . . . .. . . . 56
1.3 FinalViewonStemCellOriginDuringHumanDevelopment. . . . . 57
1.3.1 Introduction.. . . .. . . .. . . .. . . .. . . .. . . . .. . . .. . . .. . 57
1.3.2 TheOriginoftheStemCellsofGroupII. . . . . . . . . . . . . . 59
1.3.3 TypesofStemCells. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
1.3.4 FurtherStemCellCategoriesDuringtheHuman
DevelopmentalProcess:TheRôleoftheAMG-Region. . . . 64
1.3.5 HowFetalStemCellsDelivertheProgenitorCellsofthe
AdrenalCortexandHowTheyPassIntotheLocalAutonomic
Plexus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
1.3.6 TheCellsMultiplicatedintheAdrenalCortexBecomeFetal
StemCells. . .. . . . .. . . .. . . . .. . . .. . . .. . . . .. . . .. . . 66
xi