缺血性心脏病干细胞治疗进展

干细胞移植使缺血再灌注中损伤心肌的再生和修复成为可能。研究表明,移植的干细胞活性低且不能存留于心肌组织,所以再生心肌能力有限。优化干细胞移植的各环节成为缺血性心脏病受损心肌干细胞治疗的关键。该文从干细胞来源、体外诱导方法、干细胞预处理、移植方式、移植时机及移植后的监测等方面对心肌干细胞治疗进展作一介绍。     

心肌再生生物学机制研究现状

心肌组织一直被认为是不可再生组织,对其损伤后的治疗一般也只能采用保守方法.近年来,在成年大鼠心脏中发现的Lin-c-kitPOS细胞有向心肌细胞分化的潜力,说明成年机体心肌组织中仍可能存在干细胞;而对胚胎干细胞及骨髓干细胞在修复损伤心肌方面的相关研究也显示这些干细胞可通过分化成心肌细胞而改善心肌功能;对多种细胞因子的广泛研究也发现其能促进心肌细胞的分裂增生,多种研究结果提示心肌再生并非不可能.虽然在后续的几个大规模临床前研究中未能取得令人期待的结果,以及伦理问题和机体对不同干细胞的免疫排斥反应等问题仍待解决,但心肌再生的研究前景仍然光明.     

心肌再生生物学机制研究现状

心肌组织一直被认为是不可再生组织,对其损伤后的治疗一般也只能采用保守方法。近年来,在成年大鼠心脏中发现的Lin—c—kitPOS细胞有向心肌细胞分化的潜力,说明成年机体心肌组织中仍可能存在干细胞;而对胚胎干细胞及骨髓干细胞在修复损伤心肌方面的相关研究也显示这些干细胞可通过分化成心肌细胞而改善心肌功能;对多种细胞因子的广泛研究也发现其能促进心肌细胞的分裂增生,多种研究结果提示心肌再生并非不可能。虽然在后续的几个大规模临床前研究中未能取得令人期待的结果,以及伦理问题和机体对不同干细胞的免疫排斥反应等问题仍待解决,但心肌再生的研究前景仍然光明。     

心肌干细胞与心肌修复

心肌干细胞有c-kit 、MDR 和Sca-1 等多能干细胞的表面标志,体外实验证明,心肌干细胞可以分化为心肌细胞.在缺血性心脏病中,缺血、梗死区附近的心肌干细胞可以迁移、增殖,进行心肌修复.心肌干细胞还与心室肥厚和心肌衰老有关.这为心脏疾病的治疗提供了新思路:动员原位心肌干细胞.     

心肌干细胞与心肌修复

心肌干细胞有c-kit~+、MDR+和Sca-1~+等多能干细胞的表面标志,体外实验证明,心肌干细胞可以分化为心肌细胞。在缺血性心脏病中,缺血、梗死区附近的心肌干细胞可以迁移、增殖,进行心肌修复。心肌干细胞还与心室肥厚和心肌衰老有关。这为心脏疾病的治疗提供了新思路：动员原位心肌干细胞。     

干细胞再生心肌研究进展

干细胞移植使真正修复和再生心肌成为可能,是治疗缺血性心肌病的一种新方法。目前试验研究表明,由于大量移植的干细胞不能存留在心肌组织,细胞活性较低,再生心肌的能力被明显削弱。如何运用更为优化的干细胞移植策略和现实可行的方法,解决移植后干细胞再生心肌的效率成为细胞治疗的关键。此文从再生心肌的干细胞来源和选择、移植干细胞的方式、预处理千细胞提高其分化能力等方面综述当前的研究进展和前景。     

干细胞再生心肌研究进展

干细胞移植使真正修复和再生心肌成为可能,是治疗缺血性心肌病的一种新方法.目前试验研究表明,由于大量移植的干细胞不能存留在心肌组织,细胞活性较低,再生心肌的能力被明显削弱.如何运用更为优化的干细胞移植策略和现实可行的方法,解决移植后干细胞再生心肌的效率成为细胞治疗的关键.此文从再生心肌的干细胞来源和选择、移植干细胞的方式...     

急性心肌梗死与干细胞治疗

传统的观点认为心肌一旦坏死即不能再生，近年研究显示，急性心肌梗死时在细胞活性因子介导下骨髓干细胞动员、心肌归巢，分化为心肌细胞以修复坏死心肌，也可以通过激活心肌原位干细胞达到上述目的。自体或同种异体骨髓移植已用于心肌修复治疗。     

骨髓干细胞联合治疗在心肌再生领域的进展

骨髓干细胞移植是心肌再生治疗的主要方法之一,大量研究表明该类干细胞能够改善左室功能,防止心室重构,但其效率仍有待提高。许多研究尝试骨髓干细胞移植联合其它方法有效增强心肌再生治疗的效果,成为心肌再生治疗的研究热点,一些联合治疗方法显示出良好的应用前景,现综述骨髓干细胞联合治疗在心肌再生领域的进展。     

干细胞治疗对心肌修复的研究

在心血管疾病的治疗中,各种心脏疾病后心肌组织的再生修复仍是当前面临的一个严峻挑战。心肌细胞的各种自然修复过程在临床上并不能挽救受损的心肌,而干细胞治疗作为一种外源性促进心肌修复的方法,使当前的治疗从补救心肌向组织再生转变。该文从自体干细胞和异体干细胞移植两个方面,将目前应用干细胞修复受损心肌的主要策略及现况作一综述。     

间充质干细胞抗衰老研究进展

人口老龄化加重医疗负担,干细胞移植逆转衰老及其伴随的功能障碍成为治疗领域的新方法。间充质干细胞(MSC)作为兼具再生和免疫调节功能的干细胞类型,可通过直接分化的细胞替代和细胞赋能方式促进衰老组织的再生修复。最近研究发现,连续离心可分离MSC中以外泌体为代表的主要治疗载体,外泌体中衰老相关的miRNA有助于阐明MSC抗衰老治疗的分子机制。     

微环境预处理的骨髓间充质干细胞治疗大鼠心肌梗死

目的 观察骨髓间充质干细胞(BMSC)或经预处理分化的BMSC(induced BMSC,iBMSC)移植能否改善心肌梗死大鼠的心功能.方法雄性SD大鼠32只(250～300 g),分为假手术组、磷酸缓冲液(PBS)注射组、BMSC移植组和iBMSC移植组共4组,每组8只.将分离的BMSC与心肌细胞(微环境)共培养2周进行预分化,大鼠心肌梗死模型建立1周后,将BMSC或iBMSC细胞悬液注入梗死区的边缘位置.分别于细胞移植后的第1、2和4周,超声心动图检测各组大鼠心脏的左心室射血分数(LVEF),左心室舒张末期内径(LVIDd),左心室收缩末期内径(LVIDs)及短轴缩短率(FS).移植后第4周进行组织学观察,心脏组织石蜡包埋切片后采用免疫荧光技术检测移植细胞的示踪标记物及心肌标志蛋白的表达情况.结果iBMSC组LVEF在第4周时是(77.3±2.6)%,与假手术组(81.8±3.6)%比较差异无统计学意义(P＞0.05),而PBS组及BMSC组的LVEF值均低于假手术组(P均＜0.05).PBS组FS移植前后没明显变化,iBMSC组FS从移植前的(24.1±3.9)%上升到第4周的(45.1±3.1)%.M型超声心电图显示iBMSC治疗组左心室收缩能力较细胞移植前明显改善.免疫荧光分析显示,SPIO标记的移植细胞在体内表达心肌细胞标志蛋白α-辅肌动蛋白和缝隙连接蛋白43.结论经过微环境预处理的BMSC较未处理的干细胞改善心功能效果更好.这一研究为干细胞的改造与细胞移植修复心肌梗死提供了强有力的证据.     

Progenitor cells in the adult pancreas

The beta-cell mass in the adult pancreas possesses the ability to undergo limited regeneration following injury. Identifying the progenitor cells involved in this process and understanding the mechanisms leading to their maturation will open new avenues for the treatment of type 1 diabetes. However, despite steady advances in determining the molecular basis of early pancreatic development, the identification of pancreatic stem cells or beta-cell progenitors and the molecular mechanisms underlying beta-cell regeneration remain unclear. Recent advances in the directed differentiation of embryonic and adult stem cells has heightened interest in the possible application of stem cell therapy in the treatment of type 1 diabetes. Drawing on the expanding knowledge of pancreas development, beta-cell regeneration and stem cell research, this review focuses on progenitor cells in the adult pancreas as a potential source of beta-cells.     

Cell transplantation as a non-invasive strategy for treating liver fibrosis

Advancements in antiviral drugs have enabled control of viral hepatitis; yet, many patients with liver cirrhosis (LC) are awaiting liver transplants. Liver transplantation yields dramatic therapeutic effects, but problems such as shortage of donors, surgical invasiveness, immunological rejection and costs, limit the number of transplantations. Advances in liver regeneration therapy through cell transplantation as a non-invasive treatment for cirrhosis will supplement these restrictions to the number of liver transplants. Clinical trials for LC have included hematopoietic stem cell mobilization by administration of granulocyte colony-stimulating factor, infusion of autologous bone marrow cells, and administration of autologous mesenchymal stem cells derived from bone marrow or umbilical cord. Several recently reported randomized controlled studies have shown the effectiveness of these approaches. However, to promote implementation of new liver regeneration therapies, it is important to develop a system whereby cell therapies with ensured safety can be approved quickly.     

成体干细胞与肺损伤修复

尽管肺有较强的代偿能力,但如何促进肺的修复再生是提高终末肺疾病患者肺功能的关键之一。近年来应用干细胞治疗提供了我们修复组织损伤的新途径,本文就成体肺内源性干细胞和骨髓源性干细胞的生物学特性、分离培养方法及其在肺损伤中的修复作用作一综述。     

Basics and applications of stem cells in the pancreas

Enormous efforts have been made to establish pancreatic stem/progenitor cells as a source for regenerative medicine for the treatment of diabetes mellitus. In recent years, it has been recognized that the self-renewal of beta cells is the dominant process involved in postnatal beta-cell regeneration and expansion. Nevertheless, several in-vitro studies have suggested that ductal or as yet unidentified cells are candidates for pancreatic stem/progenitor cells that can differentiate into multilineage cells, including insulin⁺ cells. The question remains as to whether beta cells are generated postnatally from stem/progenitor cells other than pre-existing beta cells. Furthermore, mutated pancreatic stem cells are considered to be prospective candidates for cancer stem cells or tumor-initiating cells. This review highlights recent progress in pancreatic stem/progenitor cell research.     

Skeletal stem cells: phenotype, biology and environmental niches informing tissue regeneration

Advances in our knowledge of the biology of skeletal stem cells, together with an increased understanding of the regeneration of normal tissue offer exciting new therapeutic approaches in musculoskeletal repair. Skeletal stem cells from various adult tissues such as bone marrow can be identified and isolated based on their expression of a panel of markers associated with smooth muscle cells, pericytes and endothelial cells. Thus, skeletal stem cell-like populations within bone marrow may share a common perivascular stem cell niche within the microvascular network. To date, the environmental niche that nurtures and maintains the stromal stem cell at different anatomical sites remains poorly understood. However, an understanding of the osteogenic and perivascular niches will inform identification of the key growth factors, matrix constituents and physiological conditions that will enhance the ex vivo amplification and differentiation of osteogenic stem cells to mimic native tissue critical for tissue repair. This review will examine skeletal stem cell biology, the advances in our understanding of the skeletal and perivascular niche and interactions therein and the opportunities to harness that knowledge for musculoskeletal regeneration.     

Stem cell therapies for systemic sclerosis

The presence of autoimmune diseases, including Systemic Sclerosis (SSc), suggest failure of the normal immune regulatory processes leading to activation and expansion of autoreactive effector immune cells. Recently, stem cell transplantation emerged as a novel rescue therapy for a variety of refractory autoimmune diseases. The therapeutic strategy involves the ablation of the aberrant self‐reactive immune cells by chemotherapy and the regeneration of a new self‐tolerant immune system formed by the transplanted stem cells. In the last few years, thousands of patients worldwide have received haematopoietic stem cell transplantation (HSCT), mostly autologous, as treatment for severe irreversible autoimmune diseases, with promising results. Here we review the results of published small series of SSc patients treated with allogeneic and autologous HSCT, as well as three randomized trials, exploring the safety and efficacy of autologous HSCT in SSc. Although the results are encouraging, nonetheless, the correct application of stem cell transplantation remains an area of active investigation. Results of larger randomized, double blind clinical trials, will certainly improve our knowledge of the appropriate clinical use of stem cell therapy in SSc patients.     

改善心肌原位干细胞治疗心肌梗死疗效的策略

虽然药物治疗、心脏介入手术及心脏搭桥手术等治疗心肌梗死（MI）的方法在不断改进,但MI仍然是全球范围内人类的主要死因。干细胞治疗作为一种可以替代梗死心肌细胞的治疗方法,已经进行了临床试验,但其改善心功能的效果十分有限。目前关于改善心肌原位干细胞（CSCs）治疗MI疗效的策略主要有：①选择更合适的CSCs;②用基因工程的方法处理CSCs;③采用不同导入CSCs的方法。本文就以上3种主要策略的最新研究进展、以CSCs治疗MI的机制以及目前存在的问题作一综述。     

The diversity and plasticity of adult hepatic progenitor cells and their niche

The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell compartments. Newly identified pericentral stem/progenitor cells residing around the central vein is responsible for maintaining hepatocyte homoeostasis in the uninjured liver. In addition, hepatic progenitor cells have been reported to contribute to liver fibrosis and cancers. What drives liver homoeostasis, regeneration and diseases is determined by the physiological and pathological conditions, and especially the hepatic progenitor cell niches which influence the fate of hepatic progenitor cells. The hepatic progenitor cell niches are special microenvironments consisting of different cell types, releasing growth factors and cytokines and receiving signals, as well as the extracellular matrix (ECM) scaffold. The hepatic progenitor cell niches maintain and regulate stem cells to ensure organ homoeostasis and regeneration. In recent studies, more evidence has been shown that hepatic cells such as hepatocytes, cholangiocytes or myofibroblasts can be induced to be oval cell-like state through transitions under some circumstance, those transitional cell types as potential liver-resident progenitor cells play important roles in liver pathophysiology. In this review, we describe and update recent advances in the diversity and plasticity of hepatic progenitor cell and their niches and discuss evidence supporting their roles in liver homoeostasis, regeneration, fibrosis and cancers.