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[Challenges towards regenerative medicine].

Regenerative medicine is a promising approach to treat patients with severe cardiac failure. Since embryonic stem cells (ES cells) easily differentiate into cardiomyocytes, ES cells are thought to be a good candidate resource for cardiac cell transplantation therapy. However, molecular mechanism of cardiac differentiation is still largely unknown. Here we discuss our present approach to understand the mechanism of cardiogenesis at the molecular level as well as novel genes and cascades that are important for cardiac differentiation. Further observation will help to establish the new strategy of regenerative medicine for patients with cardiac failure.

Animals↗

Progress and potential for regenerative medicine.

Regenerative medicine focuses on new therapies to replace or restore lost, damaged, or aging cells in the human body to restore function. This goal is being realized by collaborative efforts in nonmammalian and human development, stem cell biology, genetics, materials science, bioengineering, and tissue engineering. At present, understanding existing reparative processes in humans and exploring the latent ability to regenerate tissue remains the focus in this field. This review covers recent work in limb regeneration, fetal wound healing, stem cell biology, somatic nuclear transfer, and tissue engineering as a foundation for developing new clinical therapies to augment and stimulate human regeneration.

Guided Tissue Regeneration↗

Effect of the alternative magnetic stimulation on peripheral circulation for regenerative medicine.

Regenerative medicine for patients with peripheral atherosclerosis attracts considerable attention around the world. However, ethical problems persist in gene therapy. This study evaluates the effect of alterative magnetic stimulation on peripheral circulation. The effect of magnetic stimulation as a medical treatment was examined using a thermograph for 11 healthy volunteers. The thermograph was used to measure the rise in skin temperature. The experimental results suggested an improvement in the peripheral circulation. The results of our study suggest the effectiveness of alternative magnetic stimulation on atherosclerosis. We intend to extend our study in order to establish a methodology for regenerative medical treatment for patients with peripheral atherosclerosis. Further, we wish to advance the current research in the field of angiogenesis.

Adult↗

Tissue engineering and regenerative medicine.

Regenerative medicine is evolving toward a powerful new paradigm of functional restoration. With the ethical use of gene therapy or through the manipulation of autologous tissues, improved tissue replacements may soon be available. The promise of engineered whole organs, although fraught with technical hurdles, remains on the horizon. As these advances occur, physicians and surgeons of the twenty-first century will possess ever more powerful tools to restore form and function.

Genetic Therapy↗

[Regenerative medicine].

Regenerative medicine can be defined as the possibility to replace aged/damaged cells by genetically similar young and functional cells. This could be reached by using human embryonic stem cells, eventually from cloned human embryos, or pluripotent adult stem cells. The range of the possible differentiation fates of these latter cells has recently been shown to be strikingly large. Although considerable works remains necessary to develop this new type of medicine, to assure its efficacy and safety, it nevertheless represents one of the major medical breakthroughs expected for the future.

Adult↗

[Regenerative medicine in the fields of otolaryngology; head and neck regions].

Because of the limitations of the present medicine, regenerative medicine has greatly been hoped. Regenerative medicine is an exciting emerging branch of medicine in which cell and tissue based therapies are applied to the treatments of disease. This has been supported by the development of tissue engineering that was a complex of medicine and engineering. Tissue engineering applies the principles and methods of engineering, material science, and cell and molecular biology toward the development of viable substitutes which restore, maintain, or improve the function of human tissues. According to the doctrine of tissue engineering, tissues and organs can be regenerated by manipulating three elements: cells, scaffolds and regulation factors. Understanding and manipulating the complex relationship among these elements, however, represents the great challenge for researches and doctors who engage in regenerative medicine. On the other hand, clinical applications of it have not made progress yet except limited tissues and organs. Especially, few clinical studies have reported in the fields of otolaryngology, head and neck regions. In our research group, clinical applications in these fields based on the new concept of in situ tissue engineering have been started from 2002 after approval of the ethical committee. Tissues and/or organs for clinical applications at present are trachea, cricoid cartilage, mastoid air cells, and, peripheral nerves including facial nerve, recurrent laryngeal nerve, chorda tympani nerve and so on. This article describes the researches and clinical studies at present and in the near future of regenerative medicine in the fields of otolaryngology, head and neck regions.

Animals↗

[Regenerative medicine and plastic surgery].

Regenerative medicine recently evolved as a new medical field that includes tissue engineering, cell/system biology, nanotechnology, pharmacology, stem-cell biology, and bioengineering. Regenerative medicine targets new forms of therapy to promote and support the intrinsic, autologous, regenerative potential of human biological systems. All fields of surgery have profited from these developments, and spectacular experimental results and clinical benefits have been obtained. Plastic surgery has shown interest in regenerative medicine due to its focus on reconstructive surgery. Early on, several interdisciplinary experimental working groups were founded including plastic surgery. This overview takes a closer look at common experimental and clinical results of regenerative medicine and plastic surgery.

Animals↗

[Regenerative medicine of bone and cartilage].

Regenerative medicine, which takes advantage of the unique capacity of stem cells, is a novel medical strategy to cure irreversible organ failure. There are three important elements in regenerative medicine: cells, scaffolds and signals. Although substantial progress regarding each element has been made in the past few years, it still falls short of clinical applications. In the geriatric field, osteoporosis, osteoarthritis and periodontitis are the major targets of regenerative medicine. They are usually not life-threatening, but often severely affect QOL of elderly patients. Since elderly people have already reduced number of stem cells in bone and cartilage, we need to know the sufficient conditions for osteogenesis and chondrogenesis by comprehensively screening various conditions. We developed a marker gene system expressing green fluorescence protein (GFP) under the control of osteoblast- and chondrocyte-specific promoters. This system helps us monitor osteoblast and chondrocyte differentiation easily, precisely and non-invasively. Using this system, we are now trying to find the sufficient conditions for osteogenesis and chondrogenesis, and to discover osteogenic and chondrogenic small compounds.

Aged↗

What is regenerative medicine? Emergence of applied stem cell and developmental biology.

Regenerative medicine is an emerging, but still poorly defined, field of biomedicine. The ongoing 'regenerative medicine revolution' is based on a series of new exciting breakthrough discoveries in the field of stem cell biology and developmental biology. The main problem of regenerative medicine is not so much stem cell differentiation, isolation and lineage diversity, although these are very important issues, but rather stem cell mobilisation, recruitment and integration into functional tissues. The key issue in enhancing tissue and organ regeneration is how to mobilise circulating stem and progenitor cells and how to provide an appropriate environment ('niche') for their tissue and organo-specific recruitment, 'homing' and complete functional integration. We need to know more about basic tissue biology, tissue regeneration and the cellular and molecular mechanisms of tissue turnover (both cellular and extracellular components) at different periods of human life and in different diseases. Systematic in silico, in vitro and in vivo research is a foundation for further progress in regenerative medicine. Regenerative medicine is a rapidly advancing field that opens new and exciting opportunities for completely revolutionary therapeutic modalities and technologies. Regenerative medicine is, at its essence, an emergence of applied stem cell and developmental biology.

Animals↗

[Regenerative medicine for skin].

Regenerative tissue engineering is moving rapidly from the fundamental research to the commercial applications. A number of skin substitutes have been produced by in vitro culture techniques. The U.S. Food and Drug Administration has already approved allogeneic skin substitutes. Recently, the Japanese Ministry of Health, Labor and Welfare published the guide-line for regenerative medicine. R & D Center for Artificial Skin of Kitasato University is now the heart of the Regenerating Medical Millennium Project (skin department) of the Ministry of Health, Labor and Welfare since 2000. This center established the banking system for multi-center's clinical study in 27 hospitals across Japan, using the allogeneic cultured dermal substitute composed of hyaluronic acid and collagen spongy matrix with fibroblasts.

Cell Culture Techniques↗

Stem cell-derived chondrocytes for regenerative medicine.

The regenerative capacity of cartilage is limited. Transplantation methods used to treat cartilage lesions are based mainly on primary cultures of chondrocytes, which dedifferentiate during cultivation in vitro and lose their functional properties. Stem cells are considered as an alternative source to generate cells for two reasons: first, they can almost indefinitely divide in culture, and second, they are able to differentiate into various mature cell types. Herein, we asked the question whether chondrocytes could be differentiated from mouse embryonic stem (ES) cells to a state suitable for regenerative use. When cultivated as embryoid bodies (EBs), murine ES cells differentiate into mesenchymal progenitor cells, which progressively develop into mature, hypertrophic chondrocytes and transdifferentiate into calcifying cells recapitulating all of the cellular processes of chondrogenesis. Chondrocytes isolated from EBs exhibit a high regenerative capacity. They dedifferentiate initially in culture, but later reexpress stable characteristics of mature chondrocytes. However, in cultures of chondrocytes isolated from EBs, additional mesenchymal cell types can be observed. Mesenchymal stem (MS) cells from bone marrow have already been used in tissue engineering settings. We compared the chondrogenic differentiation of MS and ES cells.

Animals↗

[Regenerative medicine for pancreatic beta cells].

Regenerative medicine involves varying degrees of interaction among many research domains. Regenerative medical therapies based on research into organogenesis and the regeneration of injured or dysfunctional tissue using cell therapy are being developed rapidly. For the treatment of diabetes mellitus (DM), pancreatic transplantation and islet (pancreatic endocrine) cell transplantation are considered to be one form of regenerative medicine to overcome pancreatic tissue dysfunction. Recently, the effective islet cell transplantation Edmonton protocol has been established, ushering in a new era in regenerative therapy for DM. However, unresolved problems remain, including a severe donor shortage and unexpected side effects with the longterm use of some immunosuppressive agents. With continuing advances and the clinical application of fundamental therapy for DM, a pancreatic islet cell transplantation or bioartificial pancreatic transplantation system, consisting of islet (pancreatic endocrine) cell purification, pancreatic cell proliferation techniques, immunoisolative membrane technology, and an appropriate transplantation procedure, will be effective. This paper focuses on applied research on human and/or porcine pancreatic cell purification, embryonic stem cell differentiation, and pancreatic stem cell differentiation into functional insulin-producing cells.

Animals↗

DDS for anti-aging and regenerative medicine (review).

In this paper we summarized, first the present status and history of the development of research in anti-aging and regenerative medicine in Japan, and secondly some of our research using DDS in the field of both medicine. The regenerative medicine has been developed in Japan by using the fund from the Government, particularly as the Millennium Project. While anti-aging medicine developed following the social interest on it in Japan and it was influenced by American Society (A4M). Next, we summarized our research on DDS for anti-aging and regenerative medicine. In most cases we used oily or solid nanoparticles as carriers of drug. Those particles have a property of both of targeting and slow release in the DDS technology. The two properties are important for anti-aging and regenerative medicine, since drugs have to be administered safely and for long time. We applied prostaglandin E1, granulocyte-colony stimulate factor (G-CSF), and retinoid into the systems.

Aging↗

American Association of Anatomists meeting on regenerative medicine.

Several years ago, the American Association of Anatomists (AAA) launched an innovative mini-meeting format as part of their annual meeting. The AAA continued this tradition by sponsoring a 2-day mini-symposium as a part of its meeting at FASEB Experimental Biology, 2006 in San Francisco, CA, USA. This year, the mini-symposium was focused on the promising and rapidly developing field of 'regenerative medicine'. The mini-symposium on 'regenerative medicine' included four separate but thematically integrated sessions: stem cells for regenerative medicine; biomimetic matrices for regenerative medicine; endothelial-mesenchymal transformation in cardiovascular regenerative medicine; and tissue engineering technologies for regenerative medicine. The goal of these sessions was to identify progress and highlight new trends and directions in the evolving field of regenerative medicine. It was an exciting 2-day mini-symposium that reviewed the differential potential of embryonic and adult stem cells, their role in tissue turnover and possible applications in tissue regeneration; identified important evolving basic science issues, such as the role of endothelial-mesenchymal transformation and stem cell recruitment in cardiovascular regenerative medicine; and, finally, clearly demonstrated how understanding basic scientific principles can be translated into novel cell therapeutics and tissue engineering modalities. The workshop also demonstrated the multidisciplinary (speakers included stem cell and developmental biologists, chemical engineers, tissue engineers, biophysicists, mathematicians and surgeons) and international (speakers represented US, Japan, Canada, Switzerland and Korea) character of ongoing efforts in the area of regenerative medicine and stem cell biology, impressive progress in this field, and confirmed the strong potential for clinical translation of emerging regenerative medicine technologies.

Anatomy↗

Common ethical issues in regenerative medicine.

One of the common ethical issues in regenerative medicine is progress in 'componentation' (= being treated as parts) of the human body, and the enhancement of the view of such "human body parts." 'Componentation' of the human body represents a preliminary step toward commodification of the human body. The process of commodification of the human body follows the steps of 'materialization' (= being treated as a material object) [first step] -- 'componentation' [second step] -- 'resourcialization' (= being treated as resources) [third step] -- commodification [fourth step]. Transplantation medicine and artificial organ developments have dramatically exposed the potential of organs and tissues as parts, and regenerative medicine has a role in advancing 'componentation' of the human body and further enhancing the view of human body parts. The 'componentation' of the human body, regardless of the degree of regenerative medicine's contribution to it, is considered as a challenge to the traditional view of human bodies and the abstract value of "Human Dignity" in the same way or alongside the 'resourcialization' and commodification. However, in the future, a new perspective of human bodies that means "a perspective whereby human bodies, organs, tissues, and even the bodies themselves are perceived as disposable tools like disposable cameras, syringes, or contact lens" and therefore a new ethical view, suitable for a new reality, may emerge.

Biomedical Research↗

Tissue engineering and regenerative medicine: manufacturing challenges.

Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

Cell Culture Techniques↗

[Biomaterials essential to regenerative medicine].

Biomaterial is one of the most important factors to be developed in regenerative medicine. In this paper, the biomaterials essential to regenerative medicine were described. Biomaterials in regenerative medicine are classified into 5 categories; 1) Biomaterials for cell culture, 2) Biomaterials for cell inducement, 3) Biomaterials for scaffold, 4) Biomaterials for immuno-isolation, 5) Biomaterials assist to regenerative medicine. As for 1), temperature responsible gel that can take out the cultured cell sheet without use protein breakdown enzyme, is mainly introduced. Micro-photolithography to make a micro patterning for cell inducement, kinds of materials for scaffold, isolated membrane and micro capsules, carrier for cell growth factors are mentioned in 2) to 5).

Animals↗

[Third-generation biomedical materials and regenerative medicine].

OBJECTIVE: To summarize the developmental process of biomedical materials and regenerative medicine. METHODS: After reviewing and analyzing the literature concerned, we put forward the developmental direction of biomedical materials and regenerative medicine in the future. RESULTS: Biomedical materials developed from the first- and second-generations to the third-generation in the 1990s. Regenerative medicine was able to help the injured tissues and organs to be regenerated by the use of the capability of healing themselves. This kind of medicine included the technologies of the stem cells and the cloning, the tissue engineering, the substitute tissues and organs, xenotransplantation and so on. CONCLUSION: The third-generation biomaterials possess the following two properties: degradation and bioactivity; and they can help the body heal itself once implanted. Regenerative medicine is a rapidly advancing field that opens a new and exciting opportunity for completely revolutionary therapeutic modalities and technologies.

Biomedical and Dental Materials↗