The prevalence of end stage renal disease (ESRD) is dramatically increasing. It is estimated that the number of people in the United States undergoing treatment for chronic kidney disease will rise from 500,000 to two million by the year 2030. In infants and children, ESRD is commonly caused by developmental abnormalities including obstruction of the fetal urinary tract. Characterization of developing glomerular precursors including renal vesicles, C- and S-shaped bodies, and podocytes is necessary in order to determine effective ways to recapitulate ontogeny with the goal of repair. New strategies to repair damaged organs using decellularized biological scaffolds are being developed, with the hope of using cell therapy for tissue regeneration within a natural framework. Decellularized scaffolds must serve as a support for cellular interactions and not result in an immune response. This study characterizes fetal kidney development in a clinically relevant rhesus monkey model and assesses whether MHC Class I or Class II proteins remain in a decellularized kidney scaffold. This was addressed by staining fetal kidneys across gestation with hematoxylin and eosin (H&E), v and performing immunohistochemistry (IHC) and enzyme-linked immunosorbant assay (ELISA) on fresh kidneys and kidneys decellularized in 1% sodium dodecyl sulfate (SDS). Results show that renal development in the rhesus monkey mimics that in the human. Glomerular precursors are abundant in the cortex during the first and second trimesters, and by the third trimester, nearly all precursors have differentiated to mature glomeruli. Near term kidneys from the fetal rhesus monkey model of obstructive renal dysplasia show cystic glomeruli with cystic dilatation of Bowman0́9s space, and abnormal glomerular tuft development when compared with unobstructed kidneys. The podocyte marker, WT-1, is strongly expressed in the condensed mesenchyme and nephrogenic zone at the cortical border during the first and second trimesters. By the third trimester, WT-1 expression is confined to mature glomeruli. IHC and ELISA revealed that HLA-E and HLA-DR were removed from the scaffolds during decellularization, while modest amounts of HLA-DQ remained in juvenile decellularized kidney scaffolds. The results from this study add to the growing base of research concerning the use of decellularized scaffolds and will contribute to the ability to repair or replace damaged kidneys in vivo.

Regenerative approaches for congenital and acquired kidney disease have the potential to repair and restore critical cell populations, renal structures, and ultimately function of damaged kidneys. The overriding objective of the studies described in this dissertation was the development, characterization, and recellularization of a three-dimensional (3D) scaffold from rhesus monkey kidneys from different age groups. This was accomplished by optimization of decellularization methods for monkey kidney transverse sections followed by characterization of extracellular matrix (ECM) proteins and biomechanical properties. It was shown that decellularized kidney scaffolds retain expression of major ECM proteins, do not contain residual cell nuclei, and show alterations in biomechanical properties as a result of the decellularization process. Age-related differences in decellularization rate and recellularization capacity using kidney explant culture were assessed. It was found that scaffolds and renal cells from younger donors provided the best outcomes in terms of recellularization potential under the culture conditions described. Recellularization was further explored by utilizing fetal renal glomerular and tubular fractions, which demonstrated that the renal tubular fraction was more effective in recellularizing tubular structures than the glomerular fraction for recellularizing glomerular structures. Proteomics analysis of decellularized kidney scaffolds revealed the presence of several non-ECM proteins. The tissue specificity of kidney and lung scaffolds were compared and showed that the decellularized scaffolds have the ability to spatially organize cells into tissue-specific structures but do not drive tissue-specific gene expression. Lastly, recellularization of kidney scaffolds using NIH-approved human embryonic stem cells (hESC) and a dynamic culture system resulted in the generation of renal constructs that contained tubules with enzymatic activity. The research addressed in this dissertation provides key approaches to using decellularized kidney scaffolds to answer meaningful questions regarding age-related differences, tissue specificity, and tissue engineering strategies for generation of renal constructs for potential regenerative strategies.

Brought to you by the world’s leading transplantclinicians, Textbook of Organ Transplantation provides acomplete and comprehensive overview of modern transplantation inall its complexity, from basic science to gold-standard surgicaltechniques to post-operative care, and from likely outcomes toconsiderations for transplant program administration, bioethics andhealth policy. Beautifully produced in full color throughout, and with over 600high-quality illustrations, it successfully: Provides a solid overview of what transplantclinicians/surgeons do, and with topics presented in an order thata clinician will encounter them. Presents a holistic look at transplantation, foregrounding theinterrelationships between transplant team members and non-surgicalclinicians in the subspecialties relevant to pre- andpost-operative patient care, such as gastroenterology, nephrology,and cardiology. Offers a focused look at pediatric transplantation, andidentifies the ways in which it significantly differs fromtransplantation in adults. Includes coverage of essential non-clinical topics such astransplant program management and administration; research designand data collection; transplant policy and bioethical issues. Textbook of Organ Transplantation is the market-leadingand definitive transplantation reference work, and essentialreading for all transplant surgeons, transplant clinicians, programadministrators, basic and clinical investigators and any othermembers of the transplantation team responsible for the clinicalmanagement or scientific study of transplant patients.

This multidisciplinary book provides up-to-date information on clinical approaches that combine stem or progenitor cells, biomaterials and scaffolds, growth factors, and other bioactive agents in order to offer improved treatment of urologic disorders including lower urinary tract dysfunction, urinary incontinence, neurogenic bladder, and erectile dysfunction. In providing clinicians and researchers with a broad perspective on the development of regenerative medicine technologies, it will assist in the dissemination of both regenerative medicine principles and a variety of exciting therapeutic options. After an opening section addressing current developments and future perspectives in tissue engineering and regenerative medicine, fundamentals such as cell technologies, biomaterials, bioreactors, bioprinting, and decellularization are covered in detail. The remainder of the book is devoted to the description and evaluation of a range of cell and tissue applications, with individual chapters focusing on the kidney, bladder, urethra, urethral sphincter, and penis and testis.

Handbook of Tissue Engineering Scaffolds: Volume Two provides a comprehensive and authoritative review on recent advancements in the application and use of composite scaffolds in tissue engineering. Chapters focus on specific tissue/organ (mostly on the structure and anatomy), the materials used for treatment, natural composite scaffolds, synthetic composite scaffolds, fabrication techniques, innovative materials and approaches for scaffolds preparation, host response to the scaffolds, challenges and future perspectives, and more. Bringing all the information together in one major reference, the authors systematically review and summarize recent research findings, thus providing an in-depth understanding of scaffold use in different body systems.

"Fundamentals of Tissue Engineering and Regenerative Medicine" provides a complete overview of the state of the art in tissue engineering and regenerative medicine. Tissue engineering has grown tremendously during the past decade. Advances in genetic medicine and stem cell technology have significantly improved the potential to influence cell and tissue performance, and have recently expanded the field towards regenerative medicine. In recent years a number of approaches have been used routinely in daily clinical practice, others have been introduced in clinical studies, and multitudes are in the preclinical testing phase. Because of these developments, there is a need to provide comprehensive and detailed information for researchers and clinicians on this rapidly expanding field. This book offers, in a single volume, the prerequisites of a comprehensive understanding of tissue engineering and regenerative medicine. The book is conceptualized according to a didactic approach (general aspects: social, economic, and ethical considerations; basic biological aspects of regenerative medicine: stem cell medicine, biomolecules, genetic engineering; classic methods of tissue engineering: cell, tissue, organ culture; biotechnological issues: scaffolds; bioreactors, laboratory work; and an extended medical discipline oriented approach: review of clinical use in the various medical specialties). The content of the book, written in 68 chapters by the world’s leading research and clinical specialists in their discipline, represents therefore the recent intellect, experience, and state of this bio-medical field.

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. Presents a comprehensive, translational source for all aspects of renal stem cells, tissue regeneration, and stem cell therapies for renal diseases in one reference work. This will ultimately result in time savings for academic, medical and pharma researchers Experts in the renal stem cell system in kidney repair and regeneration take readers from the bench research to new therapeutic approaches, providing a common language for nephrology researchers, fellows and other stem cell researchers. This enables the discussion of development of stem cells and their use in the repair and regeneration of the kidney