Regenerative Nephrology

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.

Cover image
Title page
Table of Contents
Copyright
Dedication
Contributors
Introduction
Part I: Kidney development and regeneration
Chapter 1: Nephrogenesis in health and disease
Abstract
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
Chapter 2: Renal organogenesis in the lymph node microenvironment
Abstract
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
Conclusions
Chapter 3: In vivo clonal analysis and the kidney: Implications to regenerative nephrology
Abstract
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
Chapter 4: Nephrogenesis in malnutrition
Abstract
Introduction
Kidney development and nephrogenesis overview
Impaired nephrogenesis during maternal malnourishment
Effects of macronutrient and micronutrient deficiency on kidney development
Conclusion
Part II: Modulators of regeneration
Chapter 5: Endogenous antiinflammatory and proresolving lipid mediators in renal disease
Abstract
Introduction
Lipid mediators of inflammation
Receptor activation by SPMs
Renal inflammation, resolution, and fibrosis
From biology to therapy?
Conclusion
Chapter 6: T cells in kidney injury and regeneration
Abstract
Acknowledgments
Introduction
Conventional T cells and resident kidney T cells
Evidence of T cells in AKI and allograft kidney rejection
Mechanisms of T cells in kidney AKI
Regulatory T cells in AKI, kidney repair, and regeneration
Conclusion
Chapter 7: Monocytes and dendritic cells in injury and regeneration
Abstract
Acknowledgments
Models of kidney injury
Injury
Recovery
Failure to recover
Current therapies
Chapter 8: Mast cells in kidney regeneration
Abstract
Introduction
Basic biology of 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
Positive actions of mast cell mediators in kidney disease
Concluding remarks
Part III: Stem cells in regenerative processes
Chapter 9: Regeneration and replacement of endothelial cells and renal vascular repair
Abstract
Acknowledgments
Introduction
Endothelial impairment in acute and chronic kidney injury
Progenitor cells for repairing resident vascular endothelium
Concluding remarks, future directions
Chapter 10: Stem cells in regenerative processes: Induced pluripotent stem cells
Abstract
Acknowledgment
Introduction
iPSCs
Kidney development
Directed differentiation into kidney lineages
Expansion culture of kidney progenitors
Cell therapy
Kidney reconstruction
Disease modeling
Hurdles to overcome
Conclusions
Chapter 11: Nephroprotective effect of urine-derived stem cells for renal injury
Abstract
Introduction
Origin of urine-derived stem cells
Treatment of acute renal insufficiency
Treatment of chronic renal failure
Future directions
Chapter 12: Amniotic stem cells and their exosomes
Abstract
Acknowledgment
Introduction
The amniotic stem cell
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
Clinical trials for amniotic stem cells in renal injury
Conclusions
Chapter 13: Regenerative potential of stem-cell-derived extracellular vesicles
Abstract
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
EVs in the treatment of experimental CKD
Chapter 14: Stem cell therapies in diabetes
Abstract
Introduction
Islet cell transplantation
Mesenchymal stem cells
Human pluripotent stem cells
Differentiation of hPSCs in vitro
Clinical applications of hPSCs
Protection from immune rejection
Part IV: Causes of regenerative failure
Chapter 15: Progression of kidney disease as a maladaptive response to injury
Abstract
Mitochondria
Endoplasmic reticulum (ER) stress
Lysosomes and autophagy
Conclusion
Chapter 16: Molecular mechanisms of cellular senescence
Abstract
Acknowledgments
What is cellular senescence and why it is important?
Discovery
Triggers of cellular senescence
Cell cycle arrest
Morphological and functional changes
The SASP
Prosurvival mechanisms in cellular senescence
Dynamics and heterogeneity of the senescence phenotype
Chapter 17: Characteristics of senescent cells
Abstract
Definition of senescence
Different types of senescence
Phenotype of senescent cells and detecting cellular senescence
Functional consequences of senescence
Potential role of senescence in transplantation
Chapter 18: Stress-induced senescence of tubular cells
Abstract
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
Chapter 19: Stress-induced senescence as a forme fruste of chronic kidney disease—A case for failed regeneration
Abstract
Acknowledgments
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
Chapter 20: Premature vascular aging and senescence in chronic kidney disease
Abstract
Declaration of interest
Introduction—CKD and vascular phenotype
Premature vascular senescence in chronic kidney disease
Holistic therapeutical approaches for early vascular aging in chronic kidney disease
Conclusions
Chapter 21: Injury and regeneration in renal aging
Abstract
Acknowledgment
Introduction
Injury of aging kidney
Regeneration of aging kidney
Summary
Chapter 22: Gender-dependent mechanisms of injury and repair
Abstract
Sex hormones and mechanisms of renal injury
Sex hormones and mechanisms of repair and regeneration after injury
Conclusion
Part V: Kidney engineering
Chapter 23: Glomerular stem cells
Abstract
Introduction
Glomerular progenitor cells
Molecular pathways regulating glomerular progenitor cells in homeostasis and in response to injury
Conclusion
Chapter 24: Reconstitution of the kidney glomerular capillary wall
Abstract
Acknowledgments
Introduction
Structure and function of the glomerulus
Considerations for recapitulating the glomerular filtration barrier in vitro
Engineered model of human kidney glomerulus
Engineering a glomerulus-on-a-chip that reconstitutes human kidney glomerular function in vitro
Conclusions and outlook
Chapter 25: Microfluidic modeling of the glomerulus and tubular appartus
Abstract
Introduction
Current microphysiological models of the kidney
Design considerations
Applications
Challenges
Chapter 26: Matrix scaffolds in kidney engineering
Abstract
Introduction
Whole organ bioengineering
Renal ECM hydrogels
Bio-printing scaffolds
Bio-inks
Part VI: Emerging clinical aspects of regenerative
Chapter 27: Reprogramming toward kidney regeneration: New technologies and future promises
Abstract
Introduction
Cell plasticity
Induced pluripotent stem cells—An extreme example of cell plasticity
In vitro nephrogenesis I—A detour via iPSCs
In vitro nephrogenesis II—Capturing kidney progenitors using a synthetic niche
In situ kidney cellular regeneration
In vivo lineage reprogramming
Interspecies chimeras for kidney regeneration—A legendary mission?
Conclusion
Chapter 28: Therapeutic cell reconditioning
Abstract
Acknowledgments
Definition of cellular reconditioning
Cellular structures and metabolic pathways hampering regeneration
Structural reconditioning
Metabolic reconditioning
Pharmacologic reconditioning
The road ahead
Chapter 29: Senomorphic, senolytic, and rejuvenation therapies
Abstract
Introduction
Senomorphic drugs
Senolytic drugs
Renal rejuvenation
Chapter 30: Natural products in regeneration
Abstract
Acknowledgments
Introduction
Natural products for renal regeneration
Conclusion
Chapter 31: Nanotargeting to the kidney
Abstract
Nanoparticles in medicine
Nanoparticle pharmacokinetics
Kidney-targeted nanoparticles
Nanoparticles in the clinic
Conclusions
Chapter 32: Small molecules in regeneration
Abstract
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 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
Chapter 33: Systems biology in diagnosis and treatment of kidney disease
Abstract
Introduction
What is systems biology?
Essential concepts in systems biology
Means of interrogating biological systems
Application of systems biology in kidney health, development, and disease
Challenges
Future directions and conclusions
Chapter 34: Overview of ethical concerns raised by kidney organoids
Abstract
Kidney organoids from human pluripotent stem cells (eHSCs and iPSCs)
Kidney organoids, animal experiments, chimera, and xenotransplantation
Patient consent and therapeutic misconception
Conclusion
Chapter 35: Manufacturing challenges and solutions for regenerative medicine technologies
Abstract
Introduction: Regenerative medicine manufacturing landscape
Manufacturing challenges and solutions for regenerative medicine technologies
Business development considerations for regenerative medicine technologies
Conclusions and future vision development considerations
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Regenerative Nephrology

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Michael S. Goligorsky

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