关节软骨损伤再生修复研究进展

创伤、磨损等导致的关节软骨损伤是一种常见的疾病.由于软骨组织内缺乏血管、神经和淋巴管,关节软骨在损伤后的自我再生修复能力十分有限.保守的药物治疗和关节置换术均存在各自的局限性.完美再生修复关节软骨是治愈软骨损伤的理想状态,这仍是再生医学领域极具挑战性的难题.经历数年的发展,骨髓刺激术、骨软骨移植、软骨细胞植入和软骨组织...     

软骨再生新装置开始临床试验

近日,一种由哈佛大学医学部和日本高木产业公司共同开发的,可在接近体内环境的条件下自动培养出对膝关节活动具有重要作用的软骨细胞的装置,在美国正式进入临床试验。这种装置的原理是,将从病人体内取出的少量软骨细胞置于胶原质上进行培养,同时增加培养装置内的气压;对软骨细胞来说,由于此时与人在步行或运动时受到的刺激相同,因此细胞之间就会相互作用,从而促进软骨的再生。     

血管再生中的内皮祖细胞

循环血液里存在一种被称为内皮祖细胞(endothelial progenitor cells,EPCs)的祖细胞亚群,具有在体内外分化为成熟内皮细胞的能力。根据内皮祖细胞与其他血液细胞的粘附能力的差异和内皮祖细胞的抗原特异性,内皮祖细胞可通过贴壁培养和免疫磁珠筛选而分离获得。内皮祖细胞可特异性表达三种祖细胞分子标志：CD133、CD34和血管内皮生长因子受体-2。当内皮祖细胞分化为成熟内皮细胞后,血小板内皮细胞粘附分子-1(CD31)、血管内皮粘附素(VE-cadherin,又称CD144)和Ⅷ因子(vWF)表达将上调。越来越多的证据显示,内皮祖细胞有利于体内内皮损伤后修复和血管再生。我们的研究发现,内皮祖细胞可修复apoE-缺陷小鼠血管移植物中的损伤内皮并且在动脉血管外膜中存在大量的血管祖细胞。然而,在机体的血管再生和动脉硬化的形成进程中,这些内皮祖细胞的作用和机制还不太明确。另外,有关机体内相应心血管疾病危险因素是如何影响内皮祖细胞功能的机制也不清楚。因此,对内皮祖细胞的归巢、释放和粘附机制的进一步深入研究将有助于人们探索内皮祖细胞的基础理论和临床应用价值。     

胶质细胞的神经干细胞/祖细胞特性

近年来,关于胶质细胞有许多令人惊奇的发现。其中最令人感兴趣的是部分胶质细胞在体内外都表现出神经千细胞／祖细胞的特性,在适当条件下能分化成神经元、星形胶质细胞和／或少突胶质细胞。不仅存在于非哺乳类脊椎动物整个生命周期的放射胶质显示出这一特性,存在于成年哺乳动物脑室下区和颗粒下层的星形胶质细胞也是如此。在体外培养中,部分胶质细胞具有形成多潜能神经球的能力。在体内,胶质细胞充当前驱细胞时的命运受到细胞间相互作用、细胞因子、血脉系统、胞外基质以及基膜等所构建的微环境的影响。胶质细胞的这些特性将对神经修复产生深远影响。     

MSC与PRP对膝关节软骨再生的宏观和组织学影响

为探讨骨关节炎实验模型中骨髓间充质干细胞(MSC)和富含血小板血浆(PRP)对膝关节软骨再生的宏观和组织学影响.本研究将40只家兔随机分为4组:对照组、富血小板血浆组、自体MSC未分化组和自体MSC分化为软骨细胞组.使用胶原酶溶液用于诱导骨关节炎,并且在骨关节炎诱导后6周对每组施用治疗.治疗60 d后,对动物实施安乐死...     

胚胎干细胞向造血干/祖细胞定向诱导分化的研究进展

胚胎干细胞(embryonic stem cell,ES细胞)是指由胚胎内细胞团(inner cell mass,ICM)细胞经体外抑制培养而筛选得到的细胞,具有无限增殖潜能,在体外可以向造血细胞分化,有可能为造血干细胞移植和血细胞输注开辟新的来源．此外,ES细胞向造血干/祖细胞的定向诱导分化也为阐明哺乳动物造血发育的细胞和分子机制提供了良好的体外模型．对ES细胞向造血干/祖细胞定向分化的研究进展进行了综述．     

肺干细胞与肺再生研究进展

探寻肺干细胞来源和肺再生原理的动物实验及临床研究均有很大的进展.利用基因选择技术有效的分离、培养出纯化度较高的肺干细胞群;以及肺内原始细胞与生物兼容性较好的组织工程材料共同培养形成类肺泡细胞结构,对肺组织再生的动物实验和临床应用方面起到推进的作用.并且近年来,干细胞参与肺损伤修复的基础实验研究也有了长足的发展.现对肺干细胞与肺再生方面的最新进展做一综述.     

体外诱导小鼠胚胎干细胞产生T谱系潜能造血祖细胞的关键步骤

目的:探索体外诱导小鼠胚胎干细胞(mESC)产生具有T淋巴谱系潜能造血祖细胞的关键步骤和操作技巧,进一步明晰及优化诱导策略,提高功能性血液细胞的体外再生效率.方法:将Runx1和Hoxa9串联重组质粒转染mESC产生iR9-mESC,体外依次诱导可先后产生拟胚体(EB)、诱导性生血内皮细胞(iHEC)、诱导性造血祖细胞...     

自噬对再生中肌肉干细胞的作用

各种遗传缺陷、实质性组织损伤或外源性信号的改变均可引起骨骼肌肌肉组织的损伤,并导致各种原发性或继发性肌病。因此,了解肌肉再生中的生理过程和相关分子机制将有助于更有效的组合治疗策略。自噬最初被认为是营养物质分解的机制,随后的研究进一步发现自噬也是一种降解细胞质成分、蛋白质聚集体和细胞器的生理过程,是细胞结构的调节器,广泛参与细胞应激和分化过程。对自噬抑制的研究表明了自噬对成功的肌肉再生是必不可少的,其中一个关键机制是影响肌肉干细胞(muscle stem cells,MuSCs)的分化命运。因此,了解自噬在其中的作用将有助于更有效的临床治疗。在此,该文回顾了近年来有关自噬对肌肉再生中的MuSCs作用的文献,为通过调节自噬治疗再生缺陷性肌病提供相关参考。     

人胚胎干细胞向内皮祖细胞诱导分化及其应用研究进展

近年来,内皮细胞的应用价值不断提高,应用领域不断拓宽,但其来源有限,成为研究应用的主要障碍.胚胎干细胞在体外可分化为多种组织细胞系,有可能成为获取内皮细胞的另一来源.就人胚胎干细胞向内皮祖细胞分化、分离方法、相关分子机制及内皮祖细胞应用价值等进行阐述,以期能够引起更多的关注,推动其研究的进展.     

内皮祖细胞对急性肺损伤保护作用的研究进展

内皮祖细胞（EPC）是一种多潜能细胞,主要来源于骨髓。外周血EPC可以参与修复多种血管内皮细胞损伤的疾病。目前研究证实EPC通过动员、迁移、归巢和分化等步骤在受损的肺组织处参与内皮细胞修复,调节失控的炎症反应,增强抗氧化能力,对修复和维持肺泡毛细血管屏障的完整性起着重要作用。EPC在心血管疾病和组织工程领域应用研究的成功,为EPC在急性肺损伤的治疗提供了新的思路。     

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental model shave been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells(ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury(PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.     

Vascular wall resident progenitor cells: A review

The vessel wall has usually been thought to be relatively quiescent. But the discovery of progenitor cells in many tissues and in the vasculature itself has led to a reconsideration of the vascular biology. The presence of circulating endothelial and smooth muscle progenitors able to home to the injured vascular wall is a firm acquisition; less known is the notion, coming from embryonic and adult tissue studies, that stem cells able to differentiate into endothelial cells and smooth muscle cells also reside in the arterial wall. Moreover, the existence of a vasculogenic zone has recently been identified in adult human arteries; this niche-like zone is believed to act as a source of progenitors for postnatal vasculogenesis. From the literature it is already apparent that a complex interplay between circulating and resident vascular wall progenitors takes place during embryonal and postnatal life; a structural/functional disarray of these intimate stem cell compartments could hamper appropriate vascular repair, the development of vascular wall disease being the direct clinical consequence in adult life. This review gives an overview of adult large vessel progenitors established in the vascular wall during embryogenesis and their role in the maintenance of wall homeostasis.     

The effect of cannabichromene on adult neural stem/progenitor cells

Apart from the psychotropic compound Δ⁹-tetrahydrocannabinol (THC), evidence suggests that other non-psychotropic phytocannabinoids are also of potential clinical use. This study aimed at elucidating the effect of major non-THC phytocannabinoids on the fate of adult neural stem progenitor cells (NSPCs), which are an essential component of brain function in health as well as in pathology. We tested three compounds: cannabidiol, cannabigerol, and cannabichromene (CBC), and found that CBC has a positive effect on the viability of mouse NSPCs during differentiation in vitro. The expression of NSPC and astrocyte markers nestin and Glial fibrillary acidic protein (GFAP), respectively, was up- and down-regulated, respectively. CBC stimulated ERK1/2 phosphorylation; however, this effect had a slower onset in comparison to typical MAPK stimulation. A MEK inhibitor, U0126, antagonized the up-regulation of nestin but not the down-regulation of GFAP. Based on a previous report, we studied the potential involvement of the adenosine A1 receptor in the effect of CBC on these cells and found that the selective adenosine A1 receptor antagonist, DPCPX, counteracted both ERK1/2 phosphorylation and up-regulation of nestin by CBC, indicating that also adenosine is involved in these effects of CBC, but possibly not in CBC inhibitory effect on GFAP expression. Next, we measured ATP levels as an equilibrium marker of adenosine and found higher ATP levels during differentiation of NSPCs in the presence of CBC. Taken together, our results suggest that CBC raises the viability of NSPCs while inhibiting their differentiation into astroglia, possibly through up-regulation of ATP and adenosine signalling.     

Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells

The CD133 antigen, identified as a hematopoietic stem cell marker, appears in various human embryonic epithelia including the neural tube, gut, and kidney. We herein investigated whether CD133(+) cells isolated from human hepatocellular carcinoma cell lines possess cancer stem/progenitor cell-like properties. Among the three cell lines studied, the CD133 antigen was found to be expressed only on the surface of Huh-7 cells. CD133(+) cells from Huh-7 performed a higher in vitro proliferative potential and lower mRNA expressions of mature hepatocyte markers, glutamine synthetase and cytochrome P450 3A4, than CD133(-) population of Huh-7 cells. When either CD133(+) or CD133(-) cells were subcutaneously injected into SCID mice, CD133(+) cells formed tumors, whereas CD133(-) cells induced either a very small number of tumors or none at all. Taken together, the identification of CD133(+) cells could thus be a potentially powerful tool to investigate the tumorigenic process in the hepatoma system and to also develop effective therapies targeted against hepatocellular carcinoma.     

Myocardial regeneration potential of adipose tissue-derived stem cells

Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the underlying mechanisms for beneficial effect on cardiac function, and safety issues.     

Planarian regeneration involves distinct stem cell responses to wounds and tissue absence

Regeneration requires signaling from a wound site for detection of the wound and a mechanism that determines the nature of the injury to specify the appropriate regenerative response. Wound signals and tissue responses to wounds that elicit regeneration remain poorly understood. Planarians are able to regenerate from essentially any type of injury and present a novel system for the study of wound responses in regeneration initiation. Newly developed molecular and cellular tools now enable study of regeneration initiation using the planarian Schmidtea mediterranea. Planarian regeneration requires adult stem cells called neoblasts and amputation triggers two peaks in neoblast mitoses early in regeneration. We demonstrate that the first mitotic peak is a body-wide response to any injury and that a second, local, neoblast response is induced only when injury results in missing tissue. This second response was characterized by recruitment of neoblasts to wounds, even in areas that lack neoblasts in the intact animal. Subsequently, these neoblasts were induced to divide and differentiate near the wound, leading to formation of new tissue. We conclude that there exist two functionally distinct signaling phases of the stem cell wound response that distinguish between simple injury and situations that require the regeneration of missing tissue.     

The role of multipotential stem cells in human infantile hemangioma

Hemangioma is the most common benign vascular tumor in infants and children with unknown etiology and pathogenesis. It is characterized by rapid proliferation followed by a slow involution phase. Histological analyses of infantile hemangioma (IH) in the early proliferating phase have generated a number of developmental theories suggesting an embryonic or primitive cell origin. We here hypothesize the IH may originate from multipotential stem cells. Further investigations of these hemangioma-initiating cells may improve our understanding of their function and possibly lead to novel therapeutic modalities for hemangiomas.