Selective evolutionary pressure from the tissue microenvironment drives tumor progression

Cells grow within defined environmental niches and are subject to microenvironmental control. Outside of their niche, the environment is hostile, the normal cells lack appropriate survival signals which leads to anoikis. During tumor development and progression, malignant cells must escape the local tissue control and resist anoikis. The inherent genetic instability of tumor cells makes their phenotype very plastic, which changes under continuous environmental selection pressure. In this way the microenvironment drives the somatic evolution of the tumor. In the current review, we assess how this environmental selection pressure fits into the classical scheme of tumor progression.     

神经再生室与微环境研究的新模型

目的建立神经再生室与微环境研究模型,并介绍操作要点,对其科学性、可行性进行评估.方法将大鼠的坐骨神经于股中部切断,推剥神经外膜于远近端,使近远端的神经束露出2mm将其切除,使断端的神经束回缩至外膜内,间断缝合外膜,使断伤的神经束间留有2mm～3mm微小间室.结果术后4周见再生的神经通过微小间室,吻合处神经束排列规律连续,没有神经瘤形成.结论神经外膜再生室模型是一个自由自然的神经再生内环境,符合神经生长规律,是对以往外设的"再生室"研究神经再生的一个改进,对传统的神经吻合方法是一个完善,具有实用性和重复性.     

A Novel Possible Strategy Based on Self‐Assembly Approach to Achieve Complete Periodontal Regeneration

Limitations of current regeneration modalities underscore the importance of restoring the three‐dimensional (3D) microenvironment of periodontal development, which is able to elicit the intrinsic capacity of mesenchymal stem cells to proceed to engage in a redevelopment‐like program. With increased attention for the potential therapeutic applications of periodontal ligament stem cells (PDLSCs) in periodontal regeneration, it has been proposed that bone marrow mesenchymal stem cells (BMMSCs) are very likely another cell source of physiological repair of periodontal tissues. With this in mind, enlightened from the research targeting the fabrication of laminar structures such as liver and kidney with heterotypic stratification of cell sheets, we proposed a novel possible strategy based on self‐assembly approach, which is akin to the physiological phenomenon that occurs during organogenesis, to enhance complete reconstruction of functional complex periodontium‐organ systems. We assumed that in this strategy, using the intrinsic capacity of monodispersed cells to self‐assemble into a microtissue such as a 3D spheroid, bilayered cell pellet constructs comprising calcified bone‐forming cell pellets (i.e., BMMSCs) and cementum/PDL‐forming cell pellets (i.e., PDLSCs) would be fabricated in vitro in a tissue‐mimicking way and then implanted into periodontal defects. We hypothesize that this novel strategy might open new options to reconstruct extended periodontal defects and then achieve the ultimate goal of predictable and complete regeneration of the periodontium.     

肿瘤的微环境疗法

肿瘤的发生发展与肿瘤微环境密切相关。在多种治疗肿瘤的研究方法中,微环境疗法近年来受到学者们的广泛关注,加快了癌症治疗新方法研究的步伐。现以肿瘤微环境中的关键分子为靶点,对肿瘤的微环境治疗进行综述。主要阐述与肿瘤基质相关的微环境疗法和与炎症关联性癌症的微环境疗法,同时结合部分实验案例进行分析,为采用新方法治疗肿瘤提供了理论基础。     

大鼠肾被膜微环境对牙齿发育的诱导作用

目的 为探索一种组织工程化牙齿异位培养的理想环境,检测全牙胚、牙乳头及成釉器在肾被膜环境下的发育能力.方法 利用剖腹产取出胚龄18 d的大鼠胎儿,显微外科分离牙胚,并将之进一步分为牙乳头和成釉器两部分.使用特制玻璃移植管分别将获得的全牙胚、牙乳头及成釉器植入异体大鼠肾被膜下.2周后取出培养物,HE染色观察其发育情况.结果 在肾被膜微环境下,全牙胚在肾被膜下发育良好,形成较为完整的牙齿形态和结构,单独的牙乳头可以形成牙本质,而单独的成釉器无法形成特定形态的牙冠,也无法分化成釉质.结论 证明肾被膜下是牙齿异位生长的适宜环境,ED18后成釉器发育仍然受到牙乳头调控,与此相反,牙乳头发育不再依赖成釉器的信号.     

Mesenchymal Stem Cell Preparations—Comparing Apples and Oranges

Mesenchymal stem cells (MSC) represent a type of adult stem cells that can easily be isolated from various tissues and expanded in vitro. Past reports on their pluripotency and possible clinical applications have raised hopes and interest in MSC. Multiple designations have been given to different MSC preparations. So far MSC are poorly defined by a combination of physical, phenotypical and functional properties. As MSC could be derived from different tissues as starting material, by diverse isolation protocols, cultured and expanded in different media and conditions, the MSC preparations from different laboratories are highly heterogeneous. All of these variables might have implications (1) on the selection of cell types and the composition of heterogeneous subpopulations; (2) they can selectively favor expansion of different cell populations with totally different potentials; or (3) they might alter the long term fate of adult stem cells upon in vitro culture. The recent controversy on the multilineage differentiation potentials of some specific MSC preparations might be attributed to this lack of common standards. More precise molecular and cellular markers to define subsets of MSC and to standardize the protocols for expansion of MSC are urgently needed.     

The utilization of decellularized tendon slices to provide an inductive microenvironment for the proliferation and tenogenic differentiation of stem cells

The extracellular matrix (ECM) microenvironment for the stem cell niches, including but not limited to the biochemical composition, matrix topography, and stiffness, is crucial to stem cell proliferation and differentiation. The purpose of this study was to explore the capacity of the decellularized tendon slices (DTSs) to induce stem cell proliferation and tenogenic differentiation. Rat adult stem cells, including tendon-derived stem cells (TDSCs) and bone marrow-derived stem cells (BMSCs), were identified to have universal stem cell characteristics. The DTSs were found to retain the native tendon ECM microenvironment cues, including the inherent surface topography, well-preserved tendon ECM biochemical composition and similar stiffness to native tendon. When the TDSCs and BMSCs were cultured on the DTSs respectively, the LIVE/DEAD assay, alamarBlue^® assay, scanning electron microscopy examination and qRT-PCR analysis demonstrated that the DTSs have the capacity to support these stem cells homogeneous distribution, alignment, significant proliferation and tenogenic differentiation. Taken together, the findings of this study indicate that the DTSs can provide a naturally inductive microenvironment for the proliferation and tenogenic differentiation of TDSCs and BMSCs, supporting the use of decellularized tendon ECM as a promising and valuable approach for tendon repair/reconstruction.     

衰老大鼠模型骨髓基质细胞的生物学特点

目的探讨衰老大鼠骨髓基质细胞(BMSCs)的生物学特点,为阐释机体衰老对造血诱导微环境的影响提供实验依据。方法雄性健康SD大鼠随机分为正常组和衰老模型组。衰老模型组:大鼠皮下注射D-半乳糖120mg/kg,qd×42;正常对照组:大鼠皮下注射等时与等量生理盐水。衰老动物复制完成后第2天,分离骨髓单个核细胞(BMNCs)进行髓系造血祖细胞混合集落生成单位(CFU-Mix)培养。采用全骨髓贴壁法培养和传代BMSCs,取第3代细胞进行检测,CCK-8法测定BMSCs增殖能力;流式细胞术分析细胞周期;衰老相关β-半乳糖苷酶(SA-β-Gal)染色观察衰老BMSCs百分率;ELISA检测细胞培养上清液中白细胞介素(IL)-6、干细胞生长因子(SCF)含量;DCFH-DA荧光染色流式检测BMSC活性氧簇(ROS)水平;酶学法检测BMSCs内过氧化物丙二醛(MDA)含量和总超氧化物歧化酶(SOD)活性;Western blotting检测衰老相关蛋白P16、P21、P53表达。结果与对照组相比衰老模型组大鼠CFU-Mix集落形成数量明显降低;BMSCs增殖能力显著下降;处于G0/G1期的BMSCs比例增高、S期细胞比例降低,细胞阻滞于G1期;SA-β-Gal染色阳性的BMSCs百分率显著上升;BMSCs培养上清液中IL-6、SCF含量明显下降;BMSC内ROS、MDA氧化损伤指标上升,SOD抗氧化指标下降;衰老相关蛋白P16、P21、P53表达明显上调。结论衰老大鼠骨髓基质细胞表现衰老相关生物学改变,其机制可能与氧化损伤激活衰老信号通路有关。