Technology insight: Applications of tissue engineering and biological substitutes in urology

Patients suffering from diseased or injured organs may be treated with transplanted organs. However, there is a severe shortage of donor organs, which is worsening yearly owing to the ageing population. Scientists in the field of regenerative medicine and tissue engineering apply the principles of cell transplantation, materials science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. This article reviews recent advances in regenerative medicine and describes applications of biological substitutes that may offer novel therapies for patients with end-stage organ failure.     

Recent applications of regenerative medicine to urologic structures and related tissues

PURPOSE OF REVIEW: A severe shortage of donor tissues and organs exists, which is worsening yearly given the aging population. Currently, patients suffering from diseased and injured organs are treated with transplanted organs or cells. This paper reviews recent advances that have occurred in regenerative medicine and describes application of new technologies to treat diseased or damaged organs and tissues. RECENT FINDINGS: Although most current strategies for tissue engineering depend upon a sample of autologous cells from the diseased organ of the patient, biopsies from patients with extensive end-stage organ failure may not yield enough normal cells. In these situations, stem cells are envisioned as being an alternative source. Stem cells can be derived from discarded human embryos (human embryonic stem cells), from fetal tissue, or from adult sources (bone marrow, fat, skin). Therapeutic cloning offers a potentially limitless source of cells for tissue engineering applications. SUMMARY: Recently, scientists in the fields of regenerative medicine and tissue engineering have applied the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues.     

Therapeutic cloning applications for organ transplantation

A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.     

Repairing the chronic damaged kidney: the role of regenerative medicine

The increasing number of patients who suffer from chronic kidney diseases combined with the organ shortage have directed the attention of researchers to new alternatives in the fields of regenerative medicine including cell-based therapies and tissue bioengineering. This review of renal regenerative medicine addresses the mechanisms of action by stem cells to regenerate or repair chronically damaged renal tissue, alternative routes for their delivery, the role of biomaterials in tissue engineering, and the potential therapeutic effects of combining cell therapy with biomaterials. Despite the promise of ongoing work for therapy of chronic renal failure, caution is required as a large gap still exists between scientific knowledge and clinical translation for safe, effective stem cell-based therapies.     

Whole-organ re-engineering: a regenerative medicine approach in digestive surgery for organ replacement

Recovery from end-stage organ failure presents a challenge for the medical community, considering the limitations of extracorporeal assist devices and the shortage of donors when organ replacement is needed. There is a need for new methods to promote recovery from organ failure and regenerative medicine is an option that should be considered. Recent progress in the field of tissue engineering has opened avenues for potential clinical applications, including the use of microfluidic devices for diagnostic purposes, and bioreactors or cell/tissue-based therapies for transplantation. Early attempts to engineer tissues produced thin, planar constructs; however, recent approaches using synthetic scaffolds and decellularized tissue have achieved a more complex level of tissue organization in organs such as the urinary bladder and trachea, with some success in clinical trials. In this context, the concept of decellularization technology has been applied to produce whole organ-derived scaffolds by removing cellular content while retaining all the necessary vascular and structural cues of the native organ. In this review, we focus on organ decellularization as a new regenerative medicine approach for whole organs, which may be applied in the field of digestive surgery.     

Perspectives on regenerative therapy

Organ transplantation and artificial organs are the only effective treatments for loss of organ and tissue function. These treatments, however, are associated with serious problems such as a critical shortage of donor organs, rejection, the need for life-long immunosuppression, and unstable biocompatibility. These shortcomings have stimulated the development of tissue engineering. Tissue engineering is defined as an interdisciplinary field that applies the principles of engineering and the life sciences to the development of biological substitutes that restore, retain, or improve tissue function. Tissue engineering is composed of three factors: cells; growth factors; and scaffolds. Regenerative medicine includes two important fields: tissue engineering; and regenerative biology. Regenerative therapy is a newly developed medical therapy based on the research results of regenerative medicine. The fields of regenerative therapy includes broad areas of basic and clinical sciences, bioethics, and medical economics in addition to the area of regenerative medicine. Cell sources and cell expansion are important issues in regenerative medicine. Great efforts are being made to isolate and identify the characteristics of stem cell populations of various tissues. The use of stem cells may provide an almost limitless supply of cells for transplantation. Although there are still many important issues to be resolved, regenerative medicine has been making rapid progress using a multidisciplinary approach. The success of this approach will lead to the widespread application of regenerative therapy and may ultimately be able to replace lost tissue function in the 21st century. We should, however, keep in mind the importance of bioethics in using any new therapy.     

Regenerative medicine in orthopaedic surgery.

Regenerative medicine holds great promise for orthopaedic surgery. As surgeons continue to face challenges regarding the healing of diseased or injured musculoskeletal tissues, regenerative medicine aims to develop novel therapies that will replace, repair, or promote tissue regeneration. This review article will provide an overview of the different research areas involved in regenerative medicine, such as stem cells, bioinductive factors, and scaffolds. The potential use of stem cells for orthopaedic tissue engineering will be addressed by presenting the current progress with skeletal muscle-derived stem cells. As well, the development of a revascularized massive allograft will be described and will serve as a prototypic model of orthopaedic tissue engineering. Lastly, we will describe current approaches used to design cell instructive materials and how they can be used to promote and regulate the formation of bony tissue.     

End-stage organ failure: will regenerative medicine keep its promise?

End-stage organ failure is a major cause of death worldwide that can occur in patients of all ages and transplantation is the current standard of care for chronic end-stage disease of many organs. Despite the success of organ transplantation, it is becoming clear that there will never be enough organs made available through donation to meet the increasing demand. The past decade's rapid advancement in stem cell biology and tissue engineering generated an explosive outburst of reports that gave rise to regenerative medicine, a new field that promises to "fix" damaged organs through regeneration provided by transplanted cells, stimulation of endogenous repair mechanisms, or implantation of bioengineered tissue. Whether, and if so when, regenerative medicine will keep its promise is uncertain. As we continue to strive to find new effective solutions, alternative approaches based on the development of targeted, preventive interventions aimed at maintaining normal organ function, instead of repairing organ damage, should also be pursued.     

Tissue engineering in urology. Basic principles and application

Tissue engineering is a rather new field of science. Despite this fact, some experimental investigations have already been applied in clinical studies. Compared to other medical fields, tissue engineering in urology is well established. Tissue-engineered bulking agents and tissue-engineered bladder augments are being investigated in clinical trials. Even though the knowledge gained in recent years is promising, the results of cellular therapies need to be critically judged before being finally applied in patients. Genetic engineering and stem cell research (adult undifferentiated cells) have had major impact on the field of tissue engineering over the past 2 years. By using the technology of genetic engineering, biochemical and functional qualities of tissues may be modified. Adult stem cells may help to substitute lost tissue in an autologous fashion by isolating undifferentiated cells from the body and by differentiating them into a desired cell type. These cells may be used to form native functional tissue to replace a diseased organ or organ part.     

类器官在器官移植领域的应用前景

类器官技术是近年来生物医学领域最具突破性的前沿技术之一.作为组织干细胞在体外三维培养所形成的微型器官,类器官在组织结构、细胞类型和功能等方面与来源组织高度一致,为生物医学基础研究、药物研发以及临床精准医疗提供了理想模型,并在再生医学中展现出重要潜在价值.器官移植是治疗器官衰竭最有效的手段之一,但目前供者器官来源有限,无...     

Regenerative medicine and organ transplantation: past, present, and future

This overview traces the history of regenerative medicine pertinent to organ transplantation, illustrates potential clinical applications reported to date, and highlights progress achieved in the field of complex modular organ engineering. Regenerative medicine can now produce relatively simple tissues such as skin, bladders, vessels, urethras, and upper airways, whereas engineering or generation of complex modular organs remains a major challenge. Ex vivo organ engineering may benefit from complementary investigations in the fields of developmental biology and stem cells and transplantation before its full potential can be realized.     

The Future of Replacement and Restorative Therapies: From Organ Transplantation to Regenerative Medicine

As we continue to have severe shortages of organs for transplantation, we need to consider alternatives for the future. The most likely to make a real difference in the long term is regenerative medicine (RM), a field that has emerged from the conjunction of stem cell biology and cell therapies; gene therapy; biomaterials and tissue engineering; and organ transplantation. Transplantation and RM share the same essential goal: to replace or restore organ function. Herein I briefly review some major breakthroughs of RM that are relevant to the future of organ transplantation, with a focus on the needs of people in the developing world. A definition of RM is provided and the ethical, legal, and social issues are briefly highlighted. In conclusion, I provide a projection of what the future may be for RM.     

生物材料和再生医学的进展

目的综述生物材料和再生医学的研究与进展情况.方法广泛查阅近年有关生物材料及再生医学的文献,总结生物材料的发展历程,分析其发展方向.结果生物材料经历了从第一、二代到第三代的发展过程.再生医学是利用人类的自然治愈能力,使受到巨大创伤的机体组织或器官获得自己再生能力为目的的医学,主要包括干细胞与克隆技术、组织工程、组织器官代用品、异种器官移植.结论第三代生物材料具有生物活性和降解两种性能,在植入体内后可促进机体的再生能力,从而达到治疗效果.组织工程学提出了复制"组织"、"器官"的思想,为再生医学的崛起开辟了道路.     

Cardiovascular surgery for realization of regenerative medicine

Regenerative medicine is emerging as a new approach to the treatment of severe cardiovascular diseases that are resistant to conventional therapies. Although the type of cell transplanted (e.g., pluripotent stem cells, bone marrow-derived stem cells, skeletal myoblasts, or cardiac stem cells) influences the outcome of stem cell transplantation, the method of transplantation is also important, as the efficiency of engraftment after simple needle injection is poor. Scaffold-free cell sheet transplantation technology is one of the most promising methods in this regard. Although the results of clinical trials of stem cell therapy have been marginal to date, further elucidation of the actual mechanisms of cardiac repair following cell therapy would enhance the potential for full-scale implementation of stem cell therapy. In addition to stem cell therapy, the field of cardiovascular regenerative medicine includes interspecific chimera technology, drug delivery systems using biodegradable materials, and gene therapy. Integration of these new modalities with conventional therapies will be important to realize the goal of cardiovascular regenerative medicine tailored to the condition of each individual patient. Cardiovascular surgery would be an excellent means of carrying out this strategy and could potentially resolve the health problems of the increasing number of advanced cardiovascular patients. Herein, we review the recent basic and clinical research associated with the realization of regenerative medicine in the field of cardiovascular surgery.     

Engineering of muscle tissue

The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in health care. Tissue engineering and regenerative medicine is an emerging interdisciplinary field that applies the principles of biology and engineering to the development of viable substitutes that restore, maintain, or improve the function of human tissues and organs. Tissue engineering science has provided critical new knowledge that will deepen our understanding of the phenotype of an important category of cell types-the muscle cells-and this knowledge may enable meaningful advances in musculoskeletal tissue engineering. There are two principle strategies for the replacement of impaired muscle tissues. One approach uses the application of isolated and differentiated cells (in vivo tissue engineering), using a transport matrix for the cell delivery; the other uses in vitro-designed and pre-fabricated tissue equivalents (in vitro tissue engineering). Future developments and the decision regarding which approach is more promising depend on the elucidation of the relationships among cell growth and differentiation, the three-dimensional environment, the architecture of the cells, and gene expression of the developmental process and the survival of the cells and integration in the host in in vivo experiments. As the techniques of tissue engineering become more sophisticated and as issues such as vascularization and innervation are addressed, the usefulness of these methods for reconstructive surgery may grow significantly.     

Stem cells in urology

The shortage of donors for organ transplantation has stimulated research on stem cells as a potential resource for cell-based therapy in all human tissues. Stem cells have been used for regenerative medicine applications in many organ systems, including the genitourinary system. The potential applications for stem cell therapy have, however, been restricted by the ethical issues associated with embryonic stem cell research. Instead, scientists have explored other cell sources, including progenitor and stem cells derived from adult tissues and stem cells derived from the amniotic fluid and placenta. In addition, novel techniques for generating stem cells in the laboratory are being developed. These techniques include somatic cell nuclear transfer, in which the nucleus of an adult somatic cell is placed into an oocyte, and reprogramming of adult cells to induce stem-cell-like behavior. Such techniques are now being used in tissue engineering applications, and some of the most successful experiments have been in the field of urology. Techniques to regenerate bladder tissue have reached the clinic, and exciting progress is being made in other areas, such as regeneration of the kidney and urethra. Cell therapy as a treatment for incontinence and infertility might soon become a reality. Physicians should be optimistic that regenerative medicine and tissue engineering will one day provide mainstream treatment options for urologic disorders.     

Stem cell research and transplantation: science leading ethics

One of the most exciting developments in the biological sciences in the past decade has been the discovery and characterization of human embryonic stem cells (ESCs). The interest to transplanters is the potential applications of stem cells in regenerative medicine (RM), which may involve tissue engineering, genetic engineering, and other techniques to repair, replace, or regenerate failing tissues and organs. There is little controversy surrounding human adult stem cells. However, human ESCs are surrounded by a number of ethical controversies, the extent of which is partly dependent on their source. Those derived from currently existing embryonic stem cell lines are less controversial than those derived from "excess" embryos from in vitro fertilization (IVF) clinics, while ESCs derived from IVF embryos specifically created for the purpose are not acceptable to many people arguing from religious and other moral perspectives. Somatic cell nuclear transfer, or therapeutic cloning, must be distinguished from reproductive cloning. It holds the most promise for regenerative medicine. ESCs can also be derived from gonadal ridges of aborted fetuses. The transplant community must strive to uphold societal values in its effort to find remedies for their ailing patients and address the perennial problem of organ shortage. Transplanters also have a responsibility to engage the public in their efforts to gain public understanding and support, and policy makers must take into account public opinion. Only in this way can we realize the great potential of stem cell research for organ transplantation.     

The bridge between transplantation and regenerative medicine: Beginning a new Banff classification of tissue engineering pathology

The science of regenerative medicine is arguably older than transplantation—the first major textbook was published in 1901—and a major regenerative medicine meeting took place in 1988, three years before the first Banff transplant pathology meeting. However, the subject of regenerative medicine/tissue engineering pathology has never received focused attention. Defining and classifying tissue engineering pathology is long overdue. In the next decades, the field of transplantation will enlarge at least tenfold, through a hybrid of tissue engineering combined with existing approaches to lessening the organ shortage. Gradually, transplantation pathologists will become tissue‐(re‐) engineering pathologists with enhanced skill sets to address concerns involving the use of bioengineered organs. We outline ways of categorizing abnormalities in tissue‐engineered organs through traditional light microscopy or other modalities including biomarkers. We propose creating a new Banff classification of tissue engineering pathology to standardize and assess de novo bioengineered solid organs transplantable success in vivo. We recommend constructing a framework for a classification of tissue engineering pathology now with interdisciplinary consensus discussions to further develop and finalize the classification at future Banff Transplant Pathology meetings, in collaboration with the human cell atlas project. A possible nosology of pathologic abnormalities in tissue‐engineered organs is suggested.     

Bioengineering in organ transplantation: targeting the liver

About 27,000 deaths are registered annually in the United States due to liver disease. At this time, the only definitive treatment of hepatic failure is orthotopic transplantation. However, there is a critical shortage of organs with the total waiting list for all organs currently at 100,000 requests. The number is increasing by 5% every year. Given that only organs in pristine condition are transplantable and that the hidden demand for organs as an anti-aging solution will be many times the current figures, orthotopic transplantation will always remain a limited pool. The increasing donor organ shortage requires consideration of alternative emerging technologies. Regenerative medicine may offer novel strategies to treat patients with end-stage organ failure. The ultimate aim of cell transplantation, tissue engineering, and stem cells is to regenerate tissues and organs. With the development of whole organ decellularization methods, the equation of organ shortage may dramatically change in the near future. Decellularized organs provide the ideal transplantable scaffold with all the necessary microstructure and extracellular cues for cell attachment, differentiation, vascularization, and function. New techniques to re-engineer organs may have major implications for the fields of drug discovery, regeneration biology, and ultimately organ transplantation. In this review we have provided an overview of complementary approaches to study and enhance the success of organ repopulation strategies creating new grafts/organs for transplantation.     

Translating stem cell therapies: The role of companion animals in regenerative medicine

Veterinarians and veterinary medicine have been integral to the development of stem cell therapies. The contributions of large animal experimental models to the development and refinement of modern hematopoietic stem cell transplantation were noted nearly five decades ago. More recent advances in adult stem cell/regenerative cell therapies continue to expand knowledge of the basic biology and clinical applications of stem cells. A relatively liberal legal and ethical regulation of stem cell research in veterinary medicine has facilitated the development and in some instances clinical translation of a variety of cell‐based therapies involving hematopoietic stem cells and mesenchymal stem cells, as well as other adult regenerative cells and recently embryonic stem cells and induced pluripotent stem cells. In fact, many of the pioneering developments in these fields of stem cell research have been achieved through collaborations of veterinary and human scientists. This review aims to provide an overview of the contribution of large animal veterinary models in advancing stem cell therapies for both human and clinical veterinary applications. Moreover, in the context of the “One Health Initiative,” the role veterinary patients may play in the future evolution of stem cell therapies for both human and animal patients will be explored.