Telomeres,senescence, and hematopoietic stem cells

The replicative lifespan of normal somatic cells is restricted by the erosion of telomeres, which are protective caps at the ends of linear chromosomes. The loss of telomeres induces antiproliferative signals that eventually lead to cellular senescence. The enzyme complex telomerase can maintain telomeres, but its expression is confined to highly proliferative cells such as stem cells and tumor cells. The immense regenerative capacity of the hematopoietic system is provided by a distinct type of adult stem cell: hematopoietic stem cells (HSCs). Although blood cells have to be produced continuously throughout life, the HSC pool seems not to be spared by aging processes. Indeed, limited expression of telomerase is not sufficient to prevent telomere shortening in these cells, which is thought ultimately to limit their proliferative capacity. In this review, we discuss the relevance of telomere maintenance for the hematopoietic stem cell compartment and consider potential functions of telomerase in this context. We also present possible clinical applications of telomere manipulation in HSCs and new insights affecting the aging of the hematopoietic stem cell pool and replicative exhaustion. This work was supported by European Community Grant LSHC-CT-2004-502943 (MOL CANCER MED).     

CHITIN — A promising biomaterial for tissue engineering and stem cell technologies

Chitin, after cellulose, is the second most abundant natural polymer. With a 200-year history of scientific research, chitin is beginning to see fruitful application in the fields of stem cell and tissue engineering. To date, however, research in chitin as a biomaterial appears to lag far behind that of its close relative, chitosan, due to the perceived difficulty in processing chitin. This review presents methods to improve the processability of chitin, and goes on further to discuss the unique physicochemical and biological characteristics of chitin that favor it as a biomaterial for regenerative medicine applications. Examples of the latter are presented, with special attention on the qualities of chitin that make it inherently suitable as scaffolds and matrices for tissue engineering, stem cell propagation and differentiation.     

Enabling stem cell therapies for tissue repair: Current and future challenges

Stem cells embody the tremendous potential of the human body to develop, grow, and repair throughout life. Understanding the biologic mechanisms that underlie stem cell-mediated tissue regeneration is key to harnessing this potential. Recent advances in molecular biology, genetic engineering, and material science have broadened our understanding of stem cells and helped bring them closer to widespread clinical application. Specifically, innovative approaches to optimize how stem cells are identified, isolated, grown, and utilized will help translate these advances into effective clinical therapies. Although there is growing interest in stem cells worldwide, this enthusiasm must be tempered by the fact that these treatments remain for the most part clinically unproven. Future challenges include refining the therapeutic manipulation of stem cells, validating these technologies in randomized clinical trials, and regulating the global expansion of regenerative stem cell therapies.     

主要发达国家生物技术关键领域SCI计量对比研究

生物技术是我国战略性高新技术发展领域,也是全球各国在生物经济时代能否获胜的关键技术。本文通过科学引文索引数据库（SCI）中论文收录文献的文献计量学研究,对单克隆抗体、疫苗、重组蛋白、基因治疗、干细胞研究、组织工程、基因组学、蛋白质组学、芯片技术九类关键技术领域的全球研究分布格局进行了探讨,并结合生物医药产业链进行定标比超研究,以期发现我国在全球生物技术领域所处的位置和产业差距。研究发现美国在以上关键技术领域均处于全球绝对领先地位,而我国在某些技术领域如芯片、组织工程、组学等领域已具有一定比较优势和国际竞争能力,但在较长时期内研发和产品仍将处于跟随地位。     

种子细胞——组织工程连载之三

种子细胞也是组织工程的核心研究内容,获得足够数量和质量的种子细胞是开展体外组织工程的必要基础。用于组织工程的种子细胞必须具有形成新组织结构的能力,主要来源于自体、同种异体或异种,在具体应用时各有利弊。一些成体干细胞由于不存在伦理争议以及发育分化条件相对简单等优势是重要的种子细胞,包括造血干细胞、骨髓干细胞、神经干细胞、脂肪干细胞、皮肤干细胞。人胚胎干细胞及其组织工程要真正在临床医学中得到应用,还有很长的一段路要走。其他一些细胞也可以作为组织工程种子细胞,包括内皮细胞、上皮细胞、成纤维细胞、骨细胞、成骨细胞、角质细胞、前脂肪细胞、脂肪细胞、肌腱细胞等。这些细胞已分化,分裂能力有限,但仍应用于组织工程。理想的种子细胞具有一定标准。     

Prospects for translational regenerative medicine

Translational medicine is an evolutional concept that encompasses the rapid translation of basic research for use in clinical disease diagnosis, prevention and treatment. It follows the idea "from bench to bedside and back", and hence relies on cooperation between laboratory research and clinical care. In the past decade, translational medicine has received unprecedented attention from scientists and clinicians and its fundamental principles have penetrated throughout biomedicine, offering a sign post that guides modern medical research toward a patient-centered focus. Translational regenerative medicine is still in its infancy, and significant basic research investment has not yet achieved satisfactory clinical outcomes for patients. In particular, there are many challenges associated with the use of cell- and tissue-based products for clinical therapies. This review summarizes the transformation and global progress in translational medicine over the past decade. The current obstacles and opportunities in translational regenerative medicine are outlined in the context of stem cell therapy and tissue engineering for the safe and effective regeneration of functional tissue. This review highlights the requirement for multi-disciplinary and inter-disciplinary cooperation to ensure the development of the best possible regenerative therapies within the shortest timeframe possible for the greatest patient benefit.     

Tissue engineering: Dentin – pulp complex regeneration approaches (A review)

Dental pulp is a highly specialized tissue that preserves teeth. It is important to maintain the capabilities of dental pulp before a pulpectomy by creating a local restoration of the dentin-pulp complex from residual dental pulp. The articles identified were selected by two reviewers based on entry and exit criteria. All relevant articles indexed in PubMed, Springer, Science Direct, and Scopus with no limitations from 1961 to 2016 were searched. Factors investigated in the selected articles included the following key words: Dentin-Pulp Complex, Regeneration, Tissue Engineering, Scaffold, Stem Cell, and Growth Factors. Of the 233 abstracts retrieved, the papers which were selected had evaluated the clinical aspects of the application of dentin-pulp regeneration. Generally, this study has introduced a new approach to provoke the regeneration of the dentin-pulp complex after a pulpectomy, so that exogenous growth factors and the scaffold are able to induce cells and blood vessels from the residual dental pulp in the tooth root canal. This study further presents a new strategy for local regeneration therapy of the dentin-pulp complex. This review summarizes the current knowledge of the potential beneficial effects derived from the interaction of dental materials with the dentin-pulp complex as well as potential future developments in this exciting field.     

A novel strategy for engineering vascularized grafts in vitro

Tissue engineering is an interdisciplinary field promising new therapeutic means for replacing lost or severely damaged tissues or organs. However, the fabrication of complex engineered tissues has been hampered due to the lack of vascularization to provide sufficient blood supply after implantation. In this article, we propose using rapid prototyping technology to prefabricate a scaffold with an inside hollowed vascular system including an arterial end, a venous end and capillary networks between them. The scaffold will be 'printed' layer by layer. When printing every layer, a 'low-melting point' material will be used to form a blood vessel network and a tissue-specific material will be used outside it. Hereafter the 'low-melting point' material will be evacuated by vaporization to ensure a hollowed vessel network. Then the inside hollowed capillary network can be endothelialized by using autologous endothelial cells in a cycling bioreactor while the outside material can be embedded with tissue-special cells. In the end, the new vascularized autologous grafts could be transferred to the defect site by using microsurgical techniques to connect the grafts with the host artery and vein. The strategy would facilitate construction of complex tissue engineering if the hypothesis proved to be practical.     

Electroconductive materials as biomimetic platforms for tissue regeneration

In many diseases, tissue regeneration is compromised and/or insufficient to restore tissue/organ function. Therefore, novel regenerative therapies are being developed to enhance resident and transplanted cell proliferation and functional differentiation. Numerous biomaterials engineered to include nanocomponents have emerged as promising candidates to fulfil the need of mimicking the properties of the healthy extracellular matrix. This is particularly important for tissues that require electroconductive support to achieve optimal cellular function, such as muscles and neurons. In this review, we summarize and discuss the current state-of-the-art for electroconductive materials in tissue regeneration, with particular emphasis on materials containing nanocomponents.     

Enhancing stem cell survival in vivo for tissue repair

The ability to use progenitor cells for regenerative medicine remains an evolving but elusive clinical goal. A serious obstacle towards widespread use of stem cells for tissue regeneration is the challenges that face these cells when they are placed in vivo into a wound for therapy. These environments are hypoxic, acidic, and have an upregulation of inflammatory mediators creating a region that is hostile towards cellular survival. Within this environment, the majority of progenitor cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. In order to maximize the clinical utility of stem cells, strategies must be employed to increase the cell's ability to survive in vivo through manipulation of both the stem cell and the surrounding environment. This review focuses on current advances and techniques being used to increase in vivo stem cell survival for the purpose of tissue regeneration.     

成体干细胞在泌尿系统疾病修复与重建中的应用

干细胞是目前生命科学研究的热点方向。干细胞具有自我更新及定向分化的潜在能力。近年来,干细胞移植治疗在治疗压力性尿失禁和膀胱损伤方面已成为研究重点,不同来源的干细胞在治疗膀胱损伤已取得瞩目的研究成果。干细胞对阴茎勃起神经和海绵体血管内皮细胞起着修复保护作用。干细胞具有向多种谱系细胞转化的能力来治疗压力性尿失禁。干细胞移植为泌尿系统的神经肌肉疾病的修复重建提供了一条新途径,使认为不可修复的的神经肌肉疾病的结构修复和组织重建成为可能。干细胞包括脂肪干细胞(adipose-derived stem cells,ADSCs)、骨髓间充质干细胞(bone narrow mesenchymal stem,BMSCs)和肌源性干细胞(muscle-derived stem cell,MDSCs)等。组织工程学是一类交叉学科,主要包括综合细胞培养、材料构建和细胞种植等。组织工程技术为泌尿外科临床医师提供了一条修复乃至重建受损脏器的新思路。本文就利用干细胞作为种子细胞,对膀胱缺损、压力性尿失禁、勃起功能障碍泌尿系疾病的组织工程修复进行综述。