Stem Cell Therapy This pageintentionallyleftblank Stem Cell Therapy Practical Considerations HALA M. GABR Department of ClinicalPathology, Cairo University, Cairo, Egypt WAEL ABO EL-KHEIR Egyptian Society forProgenitor Stem Cell Research (ESPCR), Cairo,Egypt Scientific illustrator:Abdullah Mahmoud AcademicPressisanimprintofElsevier 125LondonWall,LondonEC2Y5AS,UnitedKingdom 525BStreet,Suite1650,SanDiego,CA92101,UnitedStates 50HampshireStreet,5thFloor,Cambridge,MA02139,UnitedStates TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UnitedKingdom Copyright©2023ElsevierInc.Allrightsreserved. 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ISBN:978-0-12-821569-2 ForInformationonallAcademicPresspublications visitourwebsiteathttps://www.elsevier.com/books-and-journals FigureswerecreatedusingBiorender.com Publisher:StacyMasucci AcquisitionsEditor:ElizabethBrown EditorialProjectManager:SamanthaAllard ProductionProjectManager:KiruthikaGovindaraju CoverDesigner:MarkRogers TypesetbyMPSLimited,Chennai,India Dedication This book is dedicated to our beloved family. This page intentionallyleftblank Contents Part I Stem cells: basic biology 1 1. Introduction 3 1.1 Establishingtheconceptofstemcells 3 Furtherreading 4 2. Anatomy andHistology 7 2.1 Bloodsupply 8 2.2 Niche 10 2.3 Hemopoieticstemcellniches 11 2.4 Differencesbetweenosteoblasticandvascularniches 12 2.5 Componentsofthehemopoieticstemcellniche 12 2.6 Mesenchymalstemcellniche 14 2.6.1 Bonemarrowmesenchymalstemcellniche 14 2.7 Mesenchymalstemnicheinadiposetissue 15 2.7.1 Epidermalstemcellniche 16 2.7.2 Intestinalepithelialniche 16 2.8 Nichefunctions 17 2.9 Regulationofnichefunction 17 Furtherreading 19 3. Stem cells: definition, biological types, classifications, and properties 21 3.1 Definition 21 3.2 Classification 21 3.3 Properties 22 3.3.1 Potency 22 3.3.2 Self-renewal 25 3.3.3 Stemcellplasticity 25 3.3.4 Evidenceofstemcelltransdifferentiation 27 3.3.5 Theoriesoftransdifferentiation 27 3.4 Differentiation 29 3.5 Homingandengraftment 29 3.5.1 Definition 29 3.5.2 Mechanismofhoming 30 3.5.3 Enhancedanddirectedhoming 30 vii viii Contents 3.5.4 Stemcelltrafficking 31 3.5.5 Mechanismofstemcelltrafficking 31 3.5.6 Roleofstemcelltraffickinginregeneration 32 Furtherreading 32 Part II Stem cell induced regeneration: principles and applications 4. Mechanisms of stem cell(cid:1)relatedregeneration 37 4.1 Regulationoftissueregeneration 38 4.2 Overviewofthemechanismofregeneration 38 4.2.1 Transdifferentiation 39 4.2.2 Contributiontotissueregeneration 40 4.2.3 Variationintransdifferentiationpotential 40 4.2.4 Molecularmechanismsoftransdifferentiation 41 4.3 Signalingpathwaysinvolvedinstemcelltransdifferentiation 42 Mogrifyalgorithm 43 4.4 Activationofendogenousrepairsystem 43 4.5 Inductionofangiogenesis 44 4.5.1 Variabilityinangiogenicpotentialofmesenchymal stemcells 46 4.6 Secretoryfunction 47 4.6.1 Microvesiclesandexosomes 47 4.6.2 Paracrineaction 48 4.7 Mitochondrialtransfer 49 4.7.1 Inducersoftransfer 50 4.7.2 Mechanisms 50 4.7.3 Effects 50 4.7.4 Variabilityinmitochondrialtransferaccordingtomesenchymal stemcellsource 50 4.8 Microenvironmentmodulation 51 4.9 Conclusion 53 Furtherreading 53 5. Sources of stem cells for regenerative purposes 57 5.1 Characteristicsoftheidealsourceofstemcells 57 5.2 Sourcesofmesenchymalstemcells 58 5.3 Skinmesenchymalstemcells 62 5.4 Periodontalligamentstemcells 62 Contents ix 5.4.1 Sourcesofhemopoieticstemcells 62 5.5 Cordblood 63 5.5.1 Sourcesofendothelialcells 63 5.6 Tissue-specificstemcells 64 Furtherreading 66 6. Basic concepts in stem cell therapy: stem cell therapy strategy development 69 6.1 Introduction 69 6.2 Whatisthebasicdefect? 70 6.2.1 Cellulardefects 70 6.2.2 Structuraldefects 71 6.3 Whichcelllineageisthebestforrepair?Choosingoptimum celllineage 71 6.4 Whatisthebestsourceforacelltype?Choosingtheoptimum cellsource 74 6.4.1 Hemopoieticstemcells 74 6.4.2 Mesenchymalstemcells 74 6.5 Whatistheoptimumlaboratoryprotocol? 74 6.6 Choosingtheoptimumrouteofinjection 76 6.7 Factorsaffectinghomingofstemcells 77 6.7.1 Methodstoimprovestemcellhoming 78 6.7.2 Mesenchymalstemcellhoming 78 6.8 Optimaltimingforcelltherapy 79 6.9 Optimumnumberofcellsforinjection 79 6.10 Choosingthemethodofevaluation 80 Furtherreading 80 Part III Guidelines for stem cell therapy 7. Stem Cell Therapy:Laboratory guidelines 85 7.1 Introduction 85 7.1.1 Regulatorybodies 86 7.2 Laboratoryguidelines 87 7.2.1 Structuralfacilities 88 7.2.2 Personnelqualificationsandjobdescription 94 7.3 Qualitycontrolteam 96 Furtherreading 96