干细胞理论及研究进展

干细胞是目前细胞工程研究最活跃的领域,通过对各种干细胞的界定,胚胎干细胞和成体干细胞的比较研究、以及干细胞的技术应用,揭示出干细胞尤其是胚胎干细胞在医学以及整个生命科学中的巨大潜势,乃至于引发医学领域的重大变革。     

干细胞巢研究进展

干细胞巢即干细胞周围的微环境构成,一般包括干细胞的相邻细胞、粘附分子及基质等,但不同的干细胞有不同的巢结构。干细胞巢通过不同信号途径调控着干细胞的行为,使干细胞的自我更新和分化处于平衡状态。根据近年来有关干细胞巢的研究,本文从果蝇生殖系干细胞巢、哺乳动物造血干细胞巢、肠干细胞巢、毛囊表皮干细胞巢和神经干细胞巢等五个系统分别综述了干细胞巢的构成及其对干细胞的调节作用,探讨了干细胞巢作用于干细胞的内在机制。     

利用成体干细胞治疗糖尿病

糖尿病是一类严重的代谢疾病, 正危害着世界上越来越多人口的健康。胰岛移植是一种治疗糖尿病的有效方法,却因供体缺乏和移植后免疫排斥问题制约了其广泛应用。干细胞为具有强增殖能力和多向分化潜能的细胞, 是利用细胞替代疗法治疗重大疾病的细胞来源之一, 其中成体干细胞因不存在致瘤性及伦理道德问题而被人们寄予厚望。成体胰腺干细胞在活体损伤及离体培养条件下均能产生胰岛素分泌细胞, 肝干细胞、骨髓干细胞和肠干细胞等在特定离体培养条件下或经过遗传改造后也均可产生胰岛素分泌细胞, 将这些干细胞来源的胰岛素分泌细胞移植到模型糖尿病小鼠中可以治疗糖尿病。因而, 成体干细胞可以为细胞替代疗法治疗糖尿病提供丰富的胰岛供体来源。     

BMP signaling and stem cell regulation

Stem cells play an essential role in cellular specialization and pattern formation during embryogenesis and in tissue regeneration in adults. This is mainly due to a stem cell's ability to replenish itself (self-renewal) and, at the same time, produce differentiated progeny. Realization of these special stem cell features has changed the prospective of the field. However, regulation of stem cell self-renewal and maintenance of its potentiality require a complicated regulatory network of both extracellular cues and intrinsic programs. Understanding how signaling regulates stem cell behavior will shed light on the molecular mechanisms underlying stem cell self-renewal. In this review, we focus on comparing the progress of recent research regarding the roles of the BMP signaling pathway in different stem cell systems, including embryonic stem cells, germline stem cells, hematopoietic stem cells, and intestinal stem cells. We hope this comparison, together with a brief look at other signaling pathways, will bring a more balanced view of BMP signaling in regulation of stem cell properties, and further point to a general principle that self-renewal of stem cells may require a combination of maintenance of proliferation potential, inhibition of apoptosis, and blocking of differentiation.     

Membrane glycolipids in stem cells

Stem cells, such as embryonic stem cells, hematopoietic stem cells, neural stem cells, mesenchymal stem cells, and very small embryonic-like stem cells, are undifferentiated cells that are endowed with a high potential for proliferation and the capacity for self-renewal with retention of pluri/multipotency to differentiate into their progenies. Recently, studies regarding the biological functions of glycolipids and cell surface microdomains (caveolae, lipid rafts, or glycolipid-enriched microdomains) in stem cells are emerging. In this review, we introduce the expression patterns of glycolipids and the functional roles of cell surface microdomains in stem cells.     

干细胞在 1 型糖尿病治疗中的应用研究进展

1型糖尿病（T1D）是一种慢性、多因素自身免疫性疾病,在发病过程中,会不断破坏胰岛β细胞,最终导致胰岛素分泌不足, 严重威胁人类健康。目前,根治T1D的主要方法是胰岛移植,即将移植的胰岛替代体内已被疾病破坏的胰岛细胞,以恢复正常血糖。但 是,胰岛移植供体的缺乏和移植免疫排斥反应,给胰岛移植的临床应用带来巨大挑战。近年来,干细胞治疗为T1D提供了一种新疗法, 成为T1D治疗领域新的研究热点,为该病的治疗提供了新思路。综述不同来源干细胞——胚胎干细胞、诱导多能干细胞和成体干细胞用 于治疗T1D的研究进展。     

Implications for human adipose‐derived stem cells in plastic surgery

Adipose‐derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) that possess many of the same regenerative properties as other MSCs. However, the ubiquitous presence of ADSCs and their ease of access in human tissue have led to a burgeoning field of research. The plastic surgeon is uniquely positioned to harness this technology because of the relative frequency in which they perform procedures such as liposuction and autologous fat grafting. This review examines the current landscape of ADSC isolation and identification, summarizes the current applications of ADSCs in the field of plastic surgery, discusses the risks associated with their use, current barriers to universal clinical translatability, and surveys the latest research which may help to overcome these obstacles.     

The Drosophila ovary： an active stem cell community

The authors want to change the Cover Caption of Cell Research, Volume 17, Issue 1. The corrected Cover Caption should be＂ Germline stem cells （green dots） at the tip of the Drosophila ovariole generate the germline cells of the egg chambers （large blue circles denote nurse cells）. See page 15-25 for more details.＂     

The Drosophila ovary: an active stem cell community

Only a small number of cells in adult tissues (the stem cells) possess the ability to self-renew at every cell division,while producing differentiating daughter cells to maintain tissue homeostasis for an organism's lifetime.The Drosophilaovary harbors three different types of stem cell populations (germline stem cell (GSC),somatic stem cell (SSC) andescort stem cell (ESC)) located in a simple anatomical structure known as germarium,rendering it one of the best modelsystems for studying stem cell biology due to reliable stem cell identification and available sophisticated genetic toolsfor manipulating gene functions.Particularly,the niche for the GSC is among the first and best studied ones,and studieson the GSC and its niche have made many unique contributions to a better understanding of relationships between stemcells and their niche.So far,both the GSC and the SSC have been shown to be regulated by extrinsic factors originatingfrom their niche and intrinsic factors functioning within.Multiple signaling pathways are required for controlling GSCand SSC self-renewal and differentiation,which provide unique opportunities to investigate how multiple signals fromthe niche are interpreted in the stem cell.Since the Drosophila ovary contains three types of stem cells,it also providesoutstanding opportunities to study how multiple stem cells in a given tissue work collaboratively to contribute to tissuefunction and maintenance.This review highlights recent major advances in studying Drosophila ovarian stem cells andalso discusses future directions and challenges.     

成体干细胞研究进展

近年来由于成体干细胞研究技术的突破 ,成体干细胞的多向分化潜能日益为人们所关注。尤其“横向分化”的发现 ,不仅更新了对成体干细胞的传统认识 ,而且为其临床疾病治疗奠定了基础。介绍了成体干细胞的特点及分化潜能 ,并对其临床应用作了概括性讨论。     

神经干细胞移植的临床研究进展

神经系统损伤会导致脑内神经干细胞（neural stem cells,NSCs）的扩增以实现自我修复功能,而通过外源细胞移植的方式来加速这一进程,可能是一种更有效的治疗手段。当前,神经干细胞临床研究所面临的主要问题是如何评价细胞在移植后的行为和功能。该文综述了近几年使用神经干细胞移植治疗几种主要神经系统疾病的临床研究成果,并着重关注了干细胞移植后的示踪研究。     

编者按: 干细胞研究与人类健康

干细胞作为一种具有再生各种组织器官潜能的组织细胞,在器官移植、细胞治疗、组织工程、生殖医学等多个领域的基础研究与临床应用前景广泛。干细胞研究已经成为国内外生物学研究的热点,并且是我国“十二五”期间重点支持的研究领域。为促进国家干细胞研究领域的发展,我国政府于2011年10月专门成立了国家干细胞研究指导协调委员会,以统一指导和协调我国干细胞研究领域的发展。中国科学院从2011年启动“干细胞与再生医学”先导专项,对“十二五”期间中国科学院干细胞领域的专项研究进行了重点部署。 随着科研投入力度的加大,近年来我国干细胞研究进展迅速,许多研究成果已经走在世界前沿。本刊对干细胞领域的研究也十分关注,2009年以来共发表有关论文20余篇,涉及到干细胞分化、造血干细胞、肿瘤干细胞、神经干细胞及重编程研究等多个研究方向。为促进对该领域现状及发展的了解,本期汇集了3篇述评和1篇研究论文,作为干细胞研究专题发表,以飨读者。本专题对诱导性多能干细胞、体细胞重编程、干细胞遗传操作技术等3个方面的现状和发展进行了评述,并报道了间充质干细胞成骨分化机理方面的研究成果,反映了目前干细胞研究的一个侧面。刘光慧等主要评介了基于人多潜能干细胞的人类疾病机理与治疗研究的进展,分析了该领域研究成果为人类疾病的发病机制研究和再生医学治疗带来的革命性突破。张毅等简要概括了体细胞重编程的主要方法, 并重点评介了细胞提取物处理技术的研究进展,初步阐明该技术的原理和机制,为其应用奠定基础。孟姝总结了大鼠胚胎干细胞遗传操作技术的研究进展,基于大鼠胚胎干细胞的基因敲除模型的建立,将在揭示基因的生理功能、研究人类疾病的遗传机制以及寻找新药物靶标的过程中发挥更加重要的作用。袁军等研究发现,BMP9可通过p38激酶途径调控间充质干细胞C3H10T1/2成骨分化,进一步揭示了BMP9诱导和调控间充质干细胞成骨分化的机理。 本刊欢迎和期待更多、更好的有关干细胞研究的来稿,以更广泛和深入地促进我国干细胞研究领域的学术交流。     

Prospect of mesenchymal stem cells in therapy of osteoporosis: A review

Osteoporosis is a systemic skeletal disease associated with reduced bone strong point that results in raised fracture risk, with decreased bone strength, leading to reduced bone mineral density and poor bone quality. It is the most common in older females but some men are also at high risk. Although considered as a predictable result of aging, it is can be avoidable and treatable. The existing treatment of osteoporosis mainly contains antiresorptive and anabolic agents. In spite of these improvements, concerns around unusual side-effects of antiresorptive drugs, and the lack of perfect confirmation in maintenance of their long-standing effectiveness is bring about many patients not receiving these drugs. Over the years, the stem cell-based therapy has attained substantial clinical consideration because of its potential to treat numerous diseases. The stem cell therapy has been recommended as a probable therapeutic approach for patients with osteoporosis. Even though the concept of stem cell-based therapy for osteoporosis has caught substantial attention, no clinical trial has been published on humans. The cell studies based on osteoporosis are primarily focused on osteoclastic activity and bone resorption procedures. Earlier, it was on osteoblastogenesis and in recent times, on the differentiation probable of mesenchymal stem cells. In this review, we have summarized the therapeutic role of stem cell-based strategy in osteoporosis.     

肿瘤干细胞起源及其生物学特性

肿瘤干细胞与正常成体干细胞在自我更新与增殖分化能力、表型标记和强耐药性等诸多方面存在着相类似的生物学特征,所以肿瘤干细胞被推测为肿瘤发生的细胞起源。基于肿瘤干细胞与正常干细胞之间的相似性质和肿瘤发生的分子机制,科学家建立了一系列从肿瘤组织或肿瘤细胞系分离肿瘤干细胞的实验方法和研究肿瘤干细胞起源的动物实验模型。现就目前在肿瘤干细胞起源和生物学特性领域的研究作概括阐述。     

Aspects on properties, use and ethical considerations of embryonic stem cells – A short review

Mammalian embryonic stem cells have the potential to differentiate into all cell types of an adult individual. The culturing of human embryonic stem cells renders possible studies that were previously only available in animal models. Embryonic stem cells constitute a particularly attractive tool for studies of self-renewal, commitment, differentiation, maturation and cell-cell interaction. There is currently considerable hope that studies of embryonic stem cells will lead to new therapies; either by themselves, through cell replacement strategies, or by generating results assisting other fields of research to reach clinical results. There are, however, considerable challenges to be met before embryonic stem cells can be used in large-scale clinical trials.Stem cell research is an area that has given rise to much debate internationally, within science, law and politics as well as within philosophy and ethics. The ethical attitudes expressed in the public debate over stem cell research notably divide over three important distinctions: (1) Reproductive versus therapeutic cloning; (2) Using already existing embryos versus producing new embryos for research purposes; (3) Production of embryos from eggs and sperm versus through somatic-cell nuclear transfer. The potential medical benefits that may result from embryonic stem cell research arguably support a continued development in this area. However, some opponents argue that this research offends the (relative or absolute) moral status of an unborn human. Furthermore, the research would probably prove to be a both time-consuming and very expensive method for treating disease. Thus, the questions arise whom the new technique wouldbenefit and at what cost, if ever developed. This revised version was published online in July 2006 with corrections to the Cover Date.     

诱导性多能干细胞向神经细胞分化的研究进展

诱导性多能干细胞(induced pluripotent stem cell,iPS cell)是通过转染外源特定的基因组合来诱导成体细胞重编程为类似于胚胎干细胞的一种多潜能干细胞,iPS细胞与胚胎干细胞不仅在形态上相似,而且在功能方面几乎相同.另外,iPS细胞的诞生克服了胚胎干细胞在临床应用时涉及的移植免疫排斥与伦理道德问题,因此具有重要的临床应用价值.目前iPS在治疗中枢神经系统性疾病方面的研究已取得很大进展,包括iPS细胞向神经细胞诱导分化方法的改进、分化机理的探索以及iPS细胞分化来源神经细胞在神经系统疾病模型中治疗作用的研究等.从iPS细胞的创建及特点、iPS细胞向神经细胞分化的诱导方法及研究新进展方面予以综述.     

Perivascular cells for regenerative medicine

Mesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We and others recently described that MSC originate from two types of perivascular cells, namely pericytes and adventitial cells and contain the in situ counterpart of MSC in developing and adult human organs, which can be prospectively purified using well defined cell surface markers. Pericytes encircle endothelial cells of capillaries and microvessels and express the adhesion molecule CD146 and the PDGFRβ, but lack endothelial and haematopoietic markers such as CD34, CD31, vWF (von Willebrand factor), the ligand for Ulex europaeus 1 (UEA1) and CD45 respectively. The proteoglycan NG2 is a pericyte marker exclusively associated with the arterial system. Besides its expression in smooth muscle cells, smooth muscle actin (αSMA) is also detected in subsets of pericytes. Adventitial cells surround the largest vessels and, opposite to pericytes, are not closely associated to endothelial cells. Adventitial cells express CD34 and lack αSMA and all endothelial and haematopoietic cell markers, as for pericytes. Altogether, pericytes and adventitial perivascular cells express in situ and in culture markers of MSC and display capacities to differentiate towards osteogenic, adipogenic and chondrogenic cell lineages. Importantly, adventitial cells can differentiate into pericyte‐like cells under inductive conditions in vitro. Altogether, using purified perivascular cells instead of MSC may bring higher benefits to regenerative medicine, including the possibility, for the first time, to use these cells uncultured.     

The use of adipose-derived stem cells as sheets for wound healing

Cellular therapies have shown immense promise in the treatment of nonhealing wounds. Cell sheets are an emerging strategy in tissue engineering, and these cell sheets are promising as a delivery method of mesenchymal stem cells to the wound bed. Cell sheet technology utilizes temperature dependent polymers to allow for lifting of cultured cells and extracellular matrix without the use of digestive enzymes. While mesenchymal stem cells (MSCs) have shown success in cell sheets for myocardial repair, examination of cell sheets in the field of wound healing has been limited. We previously developed a novel cell sheet composed of human adipose-derived stem cells (ASCs). Both single and triple layer cell sheets were examined in a full-thickness murine wound model. The treatment cell sheets were compared with untreated controls and analyzed at timepoints of 7, 14, 18 and 21 d. The ASC cell sheets showed increased healing at 7, 14 and 18 d, and this effect was increased in the triple layer cell sheet group. Future development of these cell sheets will focus on increasing angiogenesis in the wound bed, utilizing multiple cell types, and examining allogeneic cell sheets. Here we review our experiment, expand upon our future directions and discuss the potential of an off-the-shelf cell sheet. In the field of wound healing, such a cell sheet is both clinically and scientifically exciting.