نفروژی بازسازی‌کننده

Since the publication of the first edition of this book in 2010, an explosion of spectacular discoveries in the field of regeneration has compelled the current revisit of the field of Regenerative Nephrology. This second edition features subjects as diverse as age and gender influencing regenerative processes; mechanisms and pathways of premature cell senescence affecting kidney regeneration; the ways intrinsic regenerative processes can become subverted by noxious stressors eventuating in disease progression; novel mechanistic and engineering efforts to recreate functional kidney or its component parts; cell reprogramming and reconditioning as emerging tools of future regenerative efforts; and effects of various biologicals on kidney regeneration. These newer additions to the armamentarium of Regenerative Medicine and Nephrology have become an integral part of the second edition of the book. Cutting-edge investigations are summarized by the constellation of the most experienced contributing authors coming together from around the world under the umbrella of the second edition. A significant expansion of section on induced pluripotent cells and trajectories of their differentiation. This will be followed by mechanisms and modalities of cell reprogramming for therapeutic purposes A new section on tissue engineering of the kidney of interest to nephrologists and urologists An entire section dedicated to causes of regenerative failure with the emphasis on recent discoveries of senescent cells in kidney disease, pathologic effects of senescent cells, advents in senotherapies and rejuvenation therapies A vastly expanded section on pharmacotherapies promoting kidney regeneration, trials of engineered organs, manufacturing in regenerative medicine and smooth transition to the clinical trials, with an update on some ethical issues a7bf9528_Cover(full permission) Front-Matter_2022_Regenerative-Nephrology Contributors_2022_Regenerative-Nephrology Contributors Copyright_2022_Regenerative-Nephrology Copyright Dedication_2022_Regenerative-Nephrology Dedication 7d6e9fc7_vii(full permission) 3794f1e2_viii(full permission) 13b63927_ix(full permission) 1c8616f6_xii(full permission) 1505f526_x(full permission) 3a9f3c06_xi(full permission) Introduction_2022_Regenerative-Nephrology Introduction Chapter-1---Nephrogenesis-in-health-and-disease_2022_Regenerative-Nephrology Nephrogenesis in health and disease Introduction Experimental models Developmental events preceding kidney development Cell populations in the metanephric kidney Molecular control of kidney development: The ureteric bud/collecting duct lineage Molecular control of kidney development: The metanephric mesenchyme/nephron lineage Urinary tract development Abnormal development of the renal tract Models of renal agenesis Models of renal dysplasia Models of renal hypoplasia Urinary tract malformations Summary Acknowledgments Conflict of interest statement References Chapter-2---Renal-organogenesis-in-the-lymph-node-mi_2022_Regenerative-Nephr Renal organogenesis in the lymph node microenvironment Introduction Generation of tissue-engineered kidneys Traditional transplantation sites for experimental kidney tissue engineering The lymph node microenvironment as an alternative site for kidney tissue engineering Engraftment of mouse and human fetal primary tissues in the lymph node Engraftment of isolated or artificially created nephron progenitors in the lymph node Lymphatic cues supporting kidney organogenesis Conclusions Acknowledgments Funding References Chapter-3---In-vivo-clonal-analysis-and-the-kidney--Impl_2022_Regenerative-N In vivo clonal analysis and the kidney: Implications to regenerative nephrology Introduction Principles of in vivo lineage tracing Lineage tracing for elucidation of critical steps in nephrogenesis Postnatal lineage tracing for elucidation of homeostatic and damage-response mechanisms in the kidney Lineage tracing in the adult kidney Multicolored transgenic mice Lineage tracing in the service of renal regenerative medicine Consideration and limitations Summary References Chapter-4---Nephrogenesis-in-malnutrition_2022_Regenerative-Nephrology Nephrogenesis in malnutrition Introduction Kidney development and nephrogenesis overview Impaired nephrogenesis during maternal malnourishment Effects of macronutrient and micronutrient deficiency on kidney development Protein Lipids, fats, and fatty acids Vitamin A Vitamin B Vitamin C Vitamin D Vitamin E Zinc Iron Other minerals Conclusion References Chapter-5---Endogenous-antiinflammatory-and-proresolving_2022_Regenerative-N Endogenous antiinflammatory and proresolving lipid mediators in renal disease Introduction Lipid mediators of inflammation Receptor activation by SPMs Renal inflammation, resolution, and fibrosis From biology to therapy? Conclusion References Chapter-6---T-cells-in-kidney-injury-and-regenera_2022_Regenerative-Nephrolo T cells in kidney injury and regeneration Introduction Conventional T cells and resident kidney T cells Evidence of T cells in AKI and allograft kidney rejection T cell subpopulations in mouse kidney IRI CD4 + and CD8 + T cells in AKI Mechanisms of T cells in kidney AKI Antigen-independent versus -dependent mechanisms in kidney IRI IFN- γ and NGAL in AKI Th1/Th2 and STAT4/STAT6 pathways in kidney IRI IL-17A and Th17 in AKI Resident innate-like T cells in kidney IRI: NKT cells and innate lymphoid cells (ILCs, including NK cells, γ δ T cells, ... Invariant natural killer T (iNKT) and type II NKT cells in kidney IRI Double negative (DN) α β TCR T cells in AKI and kidney repair Innate lymphoid cells (ILCs) Mucosal-associated invariant T (MAIT) cells T cells in the cholinergic antiinflammatory pathway in AKI γ δ T cells in AKI and kidney fibrosis Regulatory T cells in AKI, kidney repair, and regeneration Treg immunosuppressive mechanisms Tregs in AKI Tregs in kidney ischemic preconditioning (IPC) Tregs in nephrotoxic AKI Tregs in septic AKI Tregs in recovery/repair from AKI Treg therapeutic approaches for AKI Tregs in kidney transplant CD4 + IL-22 + cells in kidney regeneration/repair Conclusion Acknowledgments References Chapter-7---Monocytes-and-dendritic-cells-in-injury-a_2022_Regenerative-Neph Monocytes and dendritic cells in injury and regeneration Models of kidney injury Injury Tubular epithelial cells Neutrophils Dendritic cells Macrophages Eosinophils Recovery Tubular epithelial cells Macrophages Myeloid-derived suppressor cells Failure to recover Macrophages Current therapies Acknowledgments References Chapter-8---Mast-cells-in-kidney-regeneration_2022_Regenerative-Nephrology Mast cells in kidney regeneration Introduction Basic biology of mast cells Origin, tissue distribution and heterogeneity of mast cells Mast cell mediators Receptors expressed by mast cells Model systems to study mast cell functions Positive roles of mast cells in inflammation Mast cells as regulators of immune and inflammatory reactions Inflammation and kidney diseases: A regenerative perspective MC in kidney disease Localization of mast cells in normal and pathologic kidneys MC in human renal diseases Insights from animal models Animal models to study the role of mast cells in renal disease: A general overview Mast cells in autoimmune glomerulonephritis Mast cells in acute kidney injury Mast cells in renal fibrosis Positive actions of mast cell mediators in kidney disease Fibrinolytic system Heparin MC proteases Matrix metalloproteinases Histamine Immunoregulatory properties of mast cells Growth factors Lipid derived mediators Concluding remarks References Chapter-9---Regeneration-and-replacement-of-endothelial-_2022_Regenerative-N Regeneration and replacement of endothelial cells and renal vascular repair Introduction Endothelial impairment in acute and chronic kidney injury Progenitor cells for repairing resident vascular endothelium Overview of cells that repair or regenerate vascular endothelium Historical context for defining “endothelial progenitor cells” Myeloid angiogenic cells (MACs) Definitions, lineage relationships, phenotypes, and functions Endothelial colony-forming cells (ECFCs) Definitions, lineage relationships, phenotypes, and functions Evidence for MAC and ECFC in acute and chronic kidney disease Myeloid angiogenic cells in kidney injury and repair Endothelial colony-forming cells in kidney Hypothesis: Low ECFC activity and impaired MAC activity contribute to disease progression Potential therapeutic benefit of PAC or ECFC Concluding remarks, future directions Acknowledgments References Chapter-10---Stem-cells-in-regenerative-processes--Indu_2022_Regenerative-Ne Stem cells in regenerative processes: Induced pluripotent stem cells Introduction iPSCs Kidney development Directed differentiation into kidney lineages Expansion culture of kidney progenitors Cell therapy Kidney reconstruction Disease modeling Hurdles to overcome Conclusions Acknowledgment References Chapter-11---Nephroprotective-effect-of-urine-derived-s_2022_Regenerative-Ne Nephroprotective effect of urine-derived stem cells for renal injury Introduction Origin of urine-derived stem cells Treatment of acute renal insufficiency Treatment of chronic renal failure Diabetic nephropathy models Gentamicin + ischemia model Aging-related CRF Future directions References Chapter-12---Amniotic-stem-cells-and-their-exosom_2022_Regenerative-Nephrolo Amniotic stem cells and their exosomes Introduction The amniotic stem cell The origin of amnion and amniotic stem cells Amniotic epithelial cells Amniotic mesenchymal stem cells Regenerative medicine with amniotic stem cells Amniotic stem cells ameliorate renal injury and accelerate renal repair Homing and differentiation of exogenous amniotic stem cells Paracrine and endocrine mechanism of exogenous amniotic stem cells Amniotic stem cell-derived exosomes and renal injury Introduction of exosomes Amniotic epithelial cell-derived exosomes and acute kidney injury Amniotic mesenchymal stem cell-derived exosomes and kidney injury Clinical trials for amniotic stem cells in renal injury Conclusions Acknowledgment References Chapter-13---Regenerative-potential-of-stem-cell-derive_2022_Regenerative-Ne Regenerative potential of stem-cell-derived extracellular vesicles Introduction Classification of EVs and their biogenesis Contents of EVs and their mechanism of action Paracrine action of stem-cell-derived EVs EVs in the treatment of experimental AKI Ischemia-reperfusion injury Drug-induced AKI EVs in the treatment of experimental CKD Unilateral ureter obstruction Subtotal nephrectomy Diabetic nephropathy References Chapter-14---Stem-cell-therapies-in-diabetes_2022_Regenerative-Nephrology Stem cell therapies in diabetes Introduction Islet cell transplantation Mesenchymal stem cells Human pluripotent stem cells Generation of clinical-grade hPSCs Differentiation of hPSCs in vitro Generation of kidney cells from hPSCs Generation of pancreatic β cells from hPSCs Enrichment of differentiated cells derived from hPSCs Scalable manufacturing of differentiated cells derived from hPSCs Clinical applications of hPSCs Protection from immune rejection Encapsulation Autologous transplantation Generation of universal or hypoimmunogenic hiPSCs References Chapter-15---Progression-of-kidney-disease-as-a-maladap_2022_Regenerative-Ne Progression of kidney disease as a maladaptive response to injury Mitochondria Mitochondrial fusion and fission Mitochondrial biogenesis Endoplasmic reticulum (ER) stress ER stress sensor PERK-eukaryotic initiation factor 2 α (eIF2α)-ATF4 pathway IRE1-X-box-binding protein 1 (XBP1) pathway ATF6 pathway Maladaptive UPR response in CKD Apoptosis Chronic inflammation Fibrosis Crosstalk between ER and mitochondria in maladaptive response in kidney injury Lysosomes and autophagy Conclusion References Chapter-16---Molecular-mechanisms-of-cellular-sene_2022_Regenerative-Nephrol Molecular mechanisms of cellular senescence What is cellular senescence and why it is important? Discovery Triggers of cellular senescence DNA damage, telomeres, and oxidative stress in cellular senescence Developmental or programmed senescence Cell cycle arrest Morphological and functional changes The SASP Components of SASP SASP induction and regulation Prosurvival mechanisms in cellular senescence Dynamics and heterogeneity of the senescence phenotype Acknowledgments References Chapter-17---Characteristics-of-senescent-cells_2022_Regenerative-Nephrology Characteristics of senescent cells Definition of senescence Different types of senescence Developmental senescence Replicative senescence Stress-induced senescence Phenotype of senescent cells and detecting cellular senescence Functional consequences of senescence Physiology Pathophysiology Potential role of senescence in transplantation References Chapter-18---Stress-induced-senescence-of-tubular-_2022_Regenerative-Nephrol Stress-induced senescence of tubular cells Introduction Senescence in human renal disease Evidence from animal models that senescence predisposes to chronic kidney disease Tubular senescence in Acute Kidney Injury Purported features of renal tubular epithelial senescence G2/M cell cycle arrest in response to sustained renal injury Biomarkers of tubular senescence Conclusions References Chapter-19---Stress-induced-senescence-as-a-forme-fruste-of_2022_Regenerativ Stress-induced senescence as a forme fruste of chronic kidney disease—A case for failed regeneration Introduction Multiple points of convergence between CKD and cell senescence Endostatin and tissue transglutaminase in aging kidney: A paradigm of kidney senescence with broader implications The fate of senescent cells—From rejuvenation to persistence of senescent state or cell death Local and systemic effects of senescent cells Therapeutic corollaries Acknowledgments References Chapter-20---Premature-vascular-aging-and-senescence-in_2022_Regenerative-Ne Premature vascular aging and senescence in chronic kidney disease Introduction—CKD and vascular phenotype Premature vascular senescence in chronic kidney disease Early vascular aging in chronic kidney disease Uremic retention solutes and EVA Inflammation, oxidative stress, and early vascular aging The endocrine phosphate-FGF23-klotho axis and early vascular aging The NRF2-KEAP1 axis and early vascular aging Holistic therapeutical approaches for early vascular aging in chronic kidney disease Klotho—Could it be targeted? NRF2—A cytoprotective transcription factor that can be targeted by lifestyle factors Could senolytics arrest early vascular aging in chronic kidney disease? Conclusions Declaration of interest Funding Author contributions References Chapter-21---Injury-and-regeneration-in-renal-agi_2022_Regenerative-Nephrolo Injury and regeneration in renal aging Introduction Injury of aging kidney Systemic vs renal aging Renal aging Mechanisms of aging Cell senescence Cell senescence induced by DNA alterations Autophagy in cell senescence Circulating factors in aging Cell-specific aspects of renal aging Senescence of glomerular epithelial cells Cell senescence of tubular epithelial cells Senescence in other renal cells Molecular signatures of the aging kidney Regeneration of aging kidney Cellular basis of renal regeneration Amelioration of cell senescence Targeting DNA damage Targeting mitochondria Targeting autophagy Removal of senescent cells Replacement/reprogramming of senescent cells Systemic basis of renal regeneration Circulating factors Metabolic manipulation Summary Acknowledgment References Chapter-22---Gender-dependent-mechanisms-of-injury-_2022_Regenerative-Nephro Gender-dependent mechanisms of injury and repair Sex hormones and mechanisms of renal injury Cellular metabolism Cytokines, growth factors, and vasoactive agents Cellular apoptosis Renin/angiotensin/aldosterone system Renal hemodynamics Sex hormones and mechanisms of repair and regeneration after injury Kidney Cardiovascular system Muscle Liver Nervous system Peripheral, spinal, and cranial nerves Central nervous system Conclusion References Chapter-23---Glomerular-stem-cells-_2022_Regenerative-Nephrology Glomerular stem cells ☆ Introduction Glomerular progenitor cells Molecular pathways regulating glomerular progenitor cells in homeostasis and in response to injury Conclusion References Chapter-24---Reconstitution-of-the-kidney-glomerular-_2022_Regenerative-Neph Reconstitution of the kidney glomerular capillary wall Introduction Structure and function of the glomerulus Overview of mammalian glomerulogenesis and the development of the glomerular filtration barrier Glomerular basement membrane Considerations for recapitulating the glomerular filtration barrier in vitro Engineered model of human kidney glomerulus Extracellular matrices for cell adhesion and differentiation A novel method for the directed differentiation of podocytes from human pluripotent stem cells Engineering a glomerulus-on-a-chip that reconstitutes human kidney glomerular function in vitro Design of microfluidic organ-on-a-chip devices Role of mechanical strain on tissue development and function Testing of filtration function in an engineered model of the glomerulus In vitro model of drug-induced glomerular injury and proteinuria Conclusions and outlook Acknowledgments References Chapter-25---Microfluidic-modeling-of-the-glomerulus-a_2022_Regenerative-Nep Microfluidic modeling of the glomerulus and tubular appartus Introduction Current microphysiological models of the kidney Introduction to MPS Glomerulus MPS Proximal convoluted tubule MPS Glomerulus and proximal tubule MPS Loop of Henle/distal convoluted tubule MPS/collecting duct MPS Design considerations Fabrication Lithography Micromachining 3D printing Cells Materials Applications Clinical use Commercialization Challenges References Chapter-26---Matrix-scaffolds-in-kidney-engineeri_2022_Regenerative-Nephrolo Matrix scaffolds in kidney engineering Introduction Whole organ bioengineering Rodent models Porcine models Nonhuman primate models ECM scaffolds derived from the human kidney Renal ECM hydrogels Bio-printing scaffolds Bio-inks References Chapter-27---Reprogramming-toward-kidney-regeneration--N_2022_Regenerative-N Reprogramming toward kidney regeneration: New technologies and future promises Introduction Cell plasticity Induced pluripotent stem cells—An extreme example of cell plasticity In vitro nephrogenesis I—A detour via iPSCs Direct differentiation to specific renal lineages Kidney organoids Missing pieces in the jigsaw puzzle and how to find them Disease modeling using kidney organoids—Playing to its strength In vitro nephrogenesis II—Capturing kidney progenitors using a synthetic niche In situ kidney cellular regeneration In vivo lineage reprogramming Exploiting cell fate plasticity in vivo Is in vivo lineage reprogramming a far-fetched goal for kidney regeneration? Interspecies chimeras for kidney regeneration—A legendary mission? Conclusion References Chapter-28---Therapeutic-cell-reconditioning_2022_Regenerative-Nephrology Therapeutic cell reconditioning Definition of cellular reconditioning Cellular structures and metabolic pathways hampering regeneration Structural reconditioning Metabolic reconditioning Pharmacologic reconditioning The road ahead Acknowledgments References Chapter-29---Senomorphic--senolytic--and-rejuvenatio_2022_Regenerative-Nephr Senomorphic, senolytic, and rejuvenation therapies Introduction Senomorphic drugs NF-κB/C/EBP JAK inhibitor AMPK pathway mTOR inhibition SIRT1 activators Senolytic drugs BCL-2 family PI3K/AKT Quercetin Fisetin FOXO4 Heat shock protein 90 Renal rejuvenation Effects of renal diseases on stem cell function Stem cell rescue and rejuvenation References Chapter-30---Natural-products-in-regeneration_2022_Regenerative-Nephrology Natural products in regeneration Introduction Natural products for renal regeneration Dietary or supplemental natural products for renal inflammation and fibrosis Non-flavonoid polyphenols: Curcumin, resveratrol Flavonoids: Epigallocatechin-3-gallate, rutin, quercetin, genistein Berberine Nondietary natural products for renal inflammation and fibrosis Compounds from roots of Salvia miltiorrhiza: Tanshinones and Salvianolic acids Flavonoids from roots of Scutellaria baicalensis: Baicalin, wogonin, wogonoside Ligustrazine Oxymatrine Natural compounds that promote NAD + supply NAD + production and requirements for cell and tissue health NAD + effects on renal inflammation and fibrosis NAD + effects on vascular inflammation and fibrosis Conclusion Acknowledgments References Chapter-31---Nanotargeting-to-the-kidney_2022_Regenerative-Nephrology Nanotargeting to the kidney Nanoparticles in medicine Nanoparticle pharmacokinetics Kidney-targeted nanoparticles Glomerular targeting strategies Tubule targeting strategies Nanoparticles in the clinic Nanotechnologies for cancer Iron-replacement nanoparticle therapies Nanoparticle/microparticle imaging agents siRNA delivery Antifungals Conclusions Acknowledgments Disclosures References Chapter-32---Small-molecules-in-regeneration_2022_Regenerative-Nephrology Small molecules in regeneration Characteristics of small molecule therapeutics Small molecule therapeutics targeting for AKI Regeneration Growth factors as targets of small molecule therapeutics in AKI WNT/β-catenin WNT/β-catenin in AKI Transforming growth factor-β pathway Posttranslational modifications (PTM) influence on factors in fibrosis Histone deacetylases HDAC inhibitors in various models of AKI Ischemia reperfusion injury Cisplatin Sepsis Interventional models Future of small molecule inhibitors References Chapter-33---Systems-biology-in-diagnosis-and-treatmen_2022_Regenerative-Nep Systems biology in diagnosis and treatment of kidney disease Introduction What is systems biology? Essential concepts in systems biology Data reduction strategies Adjustment for multiple corrections Ontologies Publicly available large-scale datasets and open-source software Means of interrogating biological systems DNA sequencing or the genome Gene expression profiling or transcriptomics Single-cell and single-nuclear RNA sequencing Proteomics Metabolomics Novel means of capturing histologic and pathologic data The power and potential of data integration Application of systems biology in kidney health, development, and disease Kidney health Kidney development Chronic kidney disease Diabetic kidney disease Glomerular diseases Acute kidney injury Challenges Future directions and conclusions References Chapter-34---Overview-of-ethical-concerns-raised-by-k_2022_Regenerative-Neph Overview of ethical concerns raised by kidney organoids Kidney organoids from human pluripotent stem cells (eHSCs and iPSCs) Kidney organoids, animal experiments, chimera, and xenotransplantation Patient consent and therapeutic misconception Conclusion References Chapter-35---Manufacturing-challenges-and-solutions-for-_2022_Regenerative-N Manufacturing challenges and solutions for regenerative medicine technologies Introduction: Regenerative medicine manufacturing landscape Manufacturing challenges and solutions for regenerative medicine technologies Raw material challenges and solutions Cell expansion challenges and solutions Quality control and standards challenges and solutions Automation and closed system challenges and solutions Shipping logistics and storage challenges and solutions Cost of goods challenges and solutions Business development considerations for regenerative medicine technologies Market analysis Intellectual property protection Commercialization Storage logistics Cost of final commercial product and value proposition Reimbursement Conclusions and future vision development considerations References Index_2022_Regenerative-Nephrology Index A B C D E F G H I J K L M N O P Q R S T U V W X Z 49602dd6_Back_Cover(full permission) Progression of chronic diseases in general and chronic kidney disease in particular has been traditionally viewed in the light of various contributors to development of glomerulosclerosis and tubulointerstitial scarring culminating in renal fibrosis. Indeed, this dogma prevailed for decades underscoring experimental attempts to halt fibrotic processes. Breakthrough investigations of the past few years on stem/progenitor cell involvement in organ regeneration caused a conceptual shift in tackling the mechanisms of nephrosclerosis. It has become clear that the rate of progression of chronic kidney disease is the net sum of the opposing trends: degenerative fibrotic processes and regenerative repair mechanisms. The latter part of this equation has been by and large ignored for years and only recently attracted investigative attention. This book revisits the problem of kidney disease by focusing on regenerative mechanisms in renal repair and on the ways these regenerative processes can become subverted by an intrinsic disease process eventuating in its progression. Cutting-edge investigations are summarized by the most experienced international team of experts.