Regenerative Medicine for Parkinson’s Disease

Regenerative medicine for Parkinson’s disease (PD) is expected to develop dramatically with the advancement of biotechnology as represented by induced pluripotent stem cells. Existing therapeutic strategy for PD consists of medication using L-DOPA, surgery such as deep brain stimulation and rehabilitation. Current treatment cannot stop the progression of the disease, although there is definite therapeutic effect. True neurorestoration is strongly desired by regenerative medicine. This review article describes the historical development of regenerative medicine for PD, with a focus on fetal nigral cell transplantation and glial cell line-derived neurotrophic factor infusion. Subsequently, the current status of regenerative medicine for PD in terms of cell therapy and gene therapy are reviewed. In the end, the future direction to realize regenerative medicine for PD is discussed.     

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.     

Regenerative medicine in urology

The term 'regenerative medicine' encompasses strategies for restoring or renewing tissue or organ function by: (i) in vivo tissue repair by in-growth of host cells into an acellular natural or synthetic biomaterial, (ii) implantation of tissue 'engineered'in vitro by seeding cultured cells into a biomaterial scaffold, and (iii) therapeutic cloning and stem cell-based tissue regeneration. In this article, we review recent developments underpinning the emerging science of regenerative medicine and critically assess where successful implementation of novel regenerative medicine approaches into urology practice might genuinely transform the quality of life of affected individuals. We advocate the need for an evidence-based approach supported by strong science and clinical objectivity.     

Regenerative medicine strategies

Applications of regenerative medicine technology may offer novel therapies for patients with injuries, end-stage organ failure, or other clinical problems. Currently, patients suffering from diseased and injured organs can be treated with transplanted organs. However, there is a severe shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying 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. The stem cell field is also advancing rapidly, opening new avenues for this type of therapy. For example, therapeutic cloning and cellular reprogramming may one day provide a potentially limitless source of cells for tissue engineering applications. While stem cells are still in the research phase, some therapies arising from tissue engineering endeavors have already entered the clinical setting successfully, indicating the promise regenerative medicine holds for the future.     

Regenerative medicine for urological tissues: Updated review 2018

The focus of the present review on regenerative medicine is limited; first, on a few human clinical trials carried out thus far in the urology field, and second, on more basic but important biological progress that regenerative medicine has brought us. Clinical trials for the bladder, urethra and urethral sphincter have been carried out thus far. Reconstruction with autologous cell‐seeded biomaterial failed in patients in need of bladder augmentation. The strategy succeeded for urethral reconstruction in patients who might not have required this approach. Sphincter function improvement was attained by cell therapy, but did not equal the conventional standard therapy – the artificial sphincter. The radical progress in regenerative medicine is reported in more basic stem cell technology. The strategy to induce therapeutic cells from inducible pluripotent stem cells has shed novel light on developmental biology. In vitro creation of novel kidney tissue from inducible pluripotent stem cells has been attained. Other kinds of therapeutic cells could also be induced from the inducible pluripotent stem cells. Research should be encouraged to fill the gap between patient needs and what current regenerative medicine can attain.     

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 Medizin in der Orthopädie

Therapeutic approaches in regenerative medicine, irrespective of specific fields, comprise cell therapy, tissue engineering and in situ regeneration. Regenerative orthopaedics often leads the way on the path to clinical application. In cell therapy primary cells could be replaced by adult mesenchymal stem cells exhibiting almost unlimited regeneration capacity. More sophisticated biomaterial design allowing specific control of cell morphology and tissue organisation is the current focus of advancements in tissue engineering, while signalling to cells by intelligent biomaterials is a main focus of in situ regeneration. These new approaches to the reconstruction of structures and function in damaged or dysfunctional tissue will make it more often possible to achieve a sustainable improvement in terms of real regeneration rather than an acceptable repair.     

Regenerative medicine in orthopedics using cells,scaffold, and microRNA

Cells, scaffold, and growth factors are crucially important in regenerative medicine and tissue engineering. Progress in science and technology has enabled development of these three factors, with basic research being applied clinically. In the past decade, we have investigated tissue regeneration in animal models of musculoskeletal disorders by using cells, scaffold, and delivery systems which has been relatively easy to apply and develop in clinical settings. Moreover, microRNA (miRNA), which are important in biological processes and in the pathogenesis of human diseases, have been used in research on regenerative medicine. For the cell source, we focused on mesenchymal stem cells (MSC) and CD34⁺ and CD133⁺ cells as endothelial progenitor cells for regeneration of musculoskeletal organs. These cells are accessible and safe. For less invasive and more effective therapy, we developed a novel cell-delivery system using magnetic force to accumulate cells at a desired site. Furthermore, administration of synthetic miRNA could enhance tissue regeneration. In our studies, use of these cells combined with a cell-delivery system, miRNA, scaffold, and cytokines has led to effective regeneration of musculoskeletal tissues including cartilage, bone, ligaments, muscle, peripheral nerves, and spinal cord. The current and future objective is more effective and less invasive cell-based therapy with spatial control of transplanted cells by use of an external magnetic force. Analysis of efficiency, safety, and the mechanism of tissue regeneration by cells, scaffold, and miRNA will lead to more promising regenerative medicine, involving the development of a new generation of therapy. This review will focus on our regenerative medicine research, which focuses on clinical application of cells, scaffold, and miRNA.     

Application of stems cells in wound healing—An update

Wound healing is a complex but well‐orchestrated tissue repair process composed of a series of molecular and cellular events conducted by various types of cells and extracellular matrix. Despite a variety of therapeutic strategies proposed to accelerate the healing of acute and/or chronic wounds over the past few decades, effective treatment of chronic nonhealing wounds still remains a challenge. Due to the recent advances in stem cell research, a dramatic enthusiasm has been drawn to the application of stem cells in regenerative medicine. Both embryonic and adult stem cells have prolonged self‐renewal capacity and are able to differentiate into various tissue types. Nevertheless, use of embryonic stem cells is limited, owing to ethical concerns and legal restrictions. Adult stem cells, which could be isolated from bone marrow, umbilical cord blood, adipose tissue, skin and hair follicles,are being explored extensively to facilitate the healing of both acute and chronic wounds. The current article summarizes recent research on various types of stem cell‐based strategies applied to improve wound healing. In addition, future directions of stem cell‐based therapy in wound healing have also been discussed. Finally, despite its apparent advantages, limitations and challenges of stem cell therapy are discussed.     

Gene therapy for cartilage repair

AIM: Articular cartilage has very limited intrinsic healing capacity. Although numerous attempts to repair full-thickness articular cartilage defects have been conducted, no methods have successfully regenerated long-lasting hyaline cartilage. One of the most promising procedures for cartilage repair is tissue engineering accompanied by gene therapy. METHOD: With gene therapy, genes encoding for therapeutic growth factors can be expressed at a high level in the injured site for an extended period of time. Chondrocytes have been intensively studied for cell transplantation in articular cartilage defects. RESULTS: However, recent studies have shown that chondrocytes are not the only candidate for cartilage repair. Muscle-derived cells have been found capable of delivering genes and represent a good vehicle to deliver therapeutic genes to improve cartilage repair. More importantly, recent studies have suggested the presence of pluripotent stem cells in muscle-derived cells. CONCLUSION: New techniques of cell therapy and molecular medicine for the treatment of cartilage lesions are currently undergoing clinical trials. This paper will summarize the current status of gene therapy for cartilage repair and its future application.     

Advances in cell therapy for renal failure

Cell therapy is one of the most exciting fields in translational medicine. It stands at the intersection of a variety of rapidly developing scientific disciplines: stem cell biology, immunology, tissue engineering, molecular biology, biomaterials, transplantation biology, regenerative medicine and clinical research. Cell-based therapy may develop into a new therapeutic platform to treat a vast array of clinical disorders. Blood transfusions and bone marrow transplantation are prime examples of the successful application of cell-based therapeutics; but recent advances in cellular and molecular biology have expanded the potential applications of this approach. Although recombinant genetic engineering to produce a variety of therapeutics, such as human erythropoietin and insulin has proven successful, these treatments are unable to completely correct or reverse disease states, because most common disease processes are not due to the deficiency of a single protein but develop due to alterations in the complex interactions of a variety of cell components. In these complex situations, cell-based therapy may be a more successful strategy by providing a dynamic, interactive and individualized therapeutic approach that responds to the pathophysiological condition of the patient. In this regard, cells may provide innovative methods for drug delivery of biologics, immunotherapy, and tissue regenerative or replacement engineering [Nature 392 (1998) 518-524, Nat Biotechnol 20 (2002) 339-343]. The translation of this discipline to medicinal practice has tremendous potential, but in many applications technological issues need to be overcome. Since many cell-based indications are already being evaluated in the clinic, the field appears to be on the threshold of a number of successes. This review will focus on our group's use of human stem/progenitor cells in the treatment of acute and chronic renal failure as extensions to current successful renal substitution processes of hemodialysis and hemofiltration.     

Scaffold‐Based Delivery of Nucleic Acid Therapeutics for Enhanced Bone and Cartilage Repair

Recent advances in tissue engineering have made progress toward the development of biomaterials capable of the delivery of growth factors, such as bone morphogenetic proteins, in order to promote enhanced tissue repair. However, controlling the release of these growth factors on demand and within the desired localized area is a significant challenge and the associated high costs and side effects of uncontrolled delivery have proven increasingly problematic in clinical orthopedics. Gene therapy may be a valuable tool to avoid the limitations of local delivery of growth factors. Following a series of setbacks in the 1990s, the field of gene therapy is now seeing improvements in safety and efficacy resulting in substantial clinical progress and a resurgence in confidence. Biomaterial scaffold‐mediated gene therapy provides a template for cell infiltration and tissue formation while promoting transfection of cells to engineer therapeutic proteins in a sustained but ultimately transient fashion. Additionally, scaffold‐mediated delivery of RNA‐based therapeutics can silence specific genes associated with orthopedic pathological states. This review will provide an overview of the current state‐of‐the‐art in the field of gene‐activated scaffolds and their use within orthopedic tissue engineering applications. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1671–1680, 2019     

Enhanced sciatic nerve regeneration with fibrin scaffold containing human endometrial stem cells and insulin encapsulated chitosan particles: An in vivo study

BackgroundBased on recent advances in tissue engineering and stem cell therapy in nervous system diseases treatments, this study aimed to investigate sciatic nerve regeneration using human endometrial stem cells (hEnSCs) encapsulated fibrin gel containing chitosan nanoparticle loaded by insulin (Ins-CPs). Stem cells and also Insulin (Ins), which is a strong signaling molecule in peripheral nerve regeneration, play an important role in neural tissue engineering.MethodsThe fibrin hydrogel scaffold containing insulin loaded chitosan particles was synthesized and characterized. Release profiles of insulin from hydrogel was determined through UV–visible spectroscopy. Also, human endometrial stem cells encapsulated in hydrogel and its cell biocompatibility were assigned. Furthermore, the sciatic nerve crush injury was carried out and prepared fibrin gel was injected at the crush injury site by an 18-gage needle. Eight and twelve weeks later, the recovery of motor and sensory function and histopathological evaluation were assessed.ResultsThe in vitro experiments showed that the insulin can promote hEnSCs proliferation within a certain concentration range. Animals' treatment confirmed that developed fibrin gel containing Ins-CPs and hEnSCs significantly improves motor function and sensory recovery. Hematoxylin and Eosin (H&E) images provided from cross-sectional and, longitudinal-sections of the harvested regenerative nerve showed that regenerative nerve fibers had been formed and accompanied with new blood vessels in the fibrin/insulin/hEnSCs group.ConclusionOur results demonstrated that the prepared hydrogel scaffolds containing insulin nanoparticles and hEnSCs could be considered as a potential biomaterial aimed at regeneration of sciatic nerves.     

Visions for regenerative medicine: interface between scientific fact and science fiction

This article gives a brief overview of the authors' views on the future development of tissue engineering with respect to the challenges both to the materials and life sciences. Emphasis will be placed on the advantages of three-dimensional bioresorbable polymers in combination with relevant molecular cues and the application of autologous stem or progenitor cells. There is a requirement for much more diversity in the synthesis of so-called "intelligent" materials, which respond to external stimuli, as well as the development of novel drug and gene delivery systems. In addition, much more basic research is necessary in developmental biology and the application of modern cell and molecular biology to biomaterial questions.     

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.     

成肌细胞在基因治疗和组织工程中的应用综述

目的探讨骨骼肌成肌细胞的生物学特性及其在基因治疗、组织工程方面的应用前景。方法回顾成肌细胞的有关研究成果,广泛查阅近期有关成肌细胞在细胞移植及其与材料复合方面的文献,综述有关内容。结果目前成肌细胞体外培养已是一个成熟的方法,其体内与体外的生物学特性已研究得较清楚。由于它能融合到宿主的肌纤维内,将目的基因介导到宿主体内,能稳定表达对应的基因产物,因此在基因治疗方面有良好的应用前景。现已在遗传性肌营养不良症及一些遗传性血液病方面有广泛研究。它与胶原等生物材料有良好的生物相容性,体外能在胶原的诱导下良好地分化,也有将其用于血管、心肌及骨骼肌组织工程方面的研究。结论成肌细胞以其特有的生物学特性将会广泛用于基因治疗及组织工程中。     

Tissue-Engineering zur Knorpelreparatur verbessert durch Gentransfer

Cartilage tissue engineering is the creation of functional substitutes of native articular cartilage in bioreactors by attaching chondrogenic cells to polymer scaffolds. One limitation of tissue engineering is the delivery of regulatory signals to cells according to specific temporal and spatial patterns. Using gene transfer techniques, polypeptide growth factor genes such as the human insulin-like growth factor I (IGF-I) gene can be transferred into chondrocytes. When these modified cells are used for cartilage tissue engineering, the resulting cartilaginous constructs have improved structural and functional characteristics compared to constructs based on nonmodified cells. The combination of cartilage tissue engineering with overexpression of potential therapeutic genes using gene transfer technologies provides a basis for the development of novel molecular therapies for the repair of cartilage defects.     

An overview of the therapeutic potential of regenerative medicine in cutaneous wound healing

The global burden of disease associated with wounds is an increasingly significant public health concern. Current treatments are often expensive, time‐consuming and limited in their efficacy in chronic wounds. The challenge of overcoming current barriers associated with wound care requires innovative management techniques. Regenerative medicine is an emerging field of research that focuses on the repair, replacement or regeneration of cells, tissues or organs to restore impaired function. This article provides an overview of the pathophysiology of wound healing and reviews the latest evidence on the application of the principal components of regenerative medicine (growth factors, stem cell transplantation, biomaterials and tissue engineering) as therapeutic targets. Improved knowledge and understanding of the pathophysiology of wound healing has pointed to new therapeutic targets. Regenerative medicine has the potential to underpin the design of specific target therapies in acute and chronic wound healing. This personalised approach could eventually reduce the burden of disease associated with wound healing. Further evidence is required in the form of large animal studies and clinical trials to assess long‐term efficacy and safety of these new treatments.     

角膜组织工程的研究进展

目的介绍并综合分析角膜组织工程的研究进展.方法通过广泛查阅近期相关文献,重点介绍组织工程角膜种子细胞的来源、选择,以及体外培养中各种生长因子对角膜细胞生长繁殖的影响;支架材料的选择和制备及各自的优缺点.结果组织工程角膜种子细胞的来源为人眼的正常角膜细胞,以胎儿角膜为佳;各种生长因子对角膜细胞的培养、生长繁殖,以及与细胞外和细胞间基质的结合有明显促进作用,其中以成纤维细胞生长因子(basic fibroblast growth factor, bFGF)、角膜细胞生长因子(keratinocyte growth factor, KGF)、转化生长因子(transforming growth factor-β1,TGF-β1)和表皮生长因子(epidermal growth factor,EGF)影响最明显.支架材料可选择动物胶原 壳聚糖、以及黏多糖等,各有其优缺点.结论组织工程角膜可以构建和移植,与受体组织相容性较好,有望成为人体角膜移植的等效物.     

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.