Building stem cell niches from the molecule up through engineered peptide materials

The native stem cell niche is a dynamic and complex microenvironment. Recapitulating this niche is a critical focus within the fields of stem cell biology, tissue engineering, and regenerative medicine and requires the development of well-defined, tunable materials. Recent biomaterial design strategies seek to create engineered matrices that interact with cells at the molecular scale and allow on-demand, cell-triggered matrix modifications. Peptide and protein engineering can accomplish these goals through the molecular-level design of bioinductive and bioresponsive materials. This brief review focuses on engineered peptide and protein materials suitable for use as in vitro neural stem cell niche mimics and in vivo central nervous system repair. A key hallmark of these materials is the immense design freedom to specify the exact amino acid sequence leading to multi-functional bulk materials with tunable properties. These advanced materials are engineered using rational design strategies to recapitulate key aspects of the native neural stem cell niche. The resulting materials often combine the advantages of biological matrices with the engineering control of synthetic polymers. Future design strategies are expected to endow these materials with multiple layers of bi-directional feedback between the cell and the matrix, which will lead to more advanced mimics of the highly dynamic neural stem cell niche.     

The brain tumor microenvironment

High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells maybe the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells,microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology.In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells,which can contribute up to 30% of a brain tumor mass,play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete.     

Experimental epilepsy affects Notch1 signalling and the stem cell pool in the dentate gyrus

Temporal lobe epilepsy (TLE) is the most frequent form of epilepsy in adults. In addition to recurrent focal seizures, patients suffer from memory loss and depression. The factors contributing to these symptoms are unknown. In recent years, adult hippocampal neurogenesis has been implicated in certain aspects of learning and memory, as well as in depression and anhedonia. Here we investigated whether the adult hippocampal stem cell niche is affected by status epilepticus in a mouse model of TLE using unilateral intrahippocampal kainic acid injection. Eight days after status epilepticus, we found a strong diminution in Notch signalling, a key pathway involved in stem cell maintenance, as assayed by hes5 reporter gene activity. In particular, hes5–GFP expression in the subgranular zone of the dentate gyrus was diminished. Furthermore, Sox2‐positive cells as well as stem cell proliferation were reduced, thus pointing to a disruption of the stem cell niche in epilepsy under the present experimental conditions.     

Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver

1. Download : Download high-res image (201KB)
2. Download : Download full-size image

     

Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses

1. Download : Download high-res image (102KB)
2. Download : Download full-size image

     

后鼓室的应用解剖学研究

以100侧成人正常颞骨标本为材料,对整个后鼓室进行形态学观察。后鼓室以锥隆起为中心,借面神经管凸,岬小桥,锥体嵴,鼓索嵴等为标志,分为卵圆窗龛后隐窝,鼓室窦,外侧鼓室窦,面经验隐窝。面经神管与面神经隐窝的关系恒定,均位于其内侧壁,埋藏较浅;面神经管乳突段与外侧鼓室窦的关系较复杂,其埋藏位置,深浅与后者的型别有关。本文提出了根据外侧鼓室窦型别预测面神经乳突段的方法。还对鼓索嵴,岬小桥,锥体嵴的形态改变对后鼓室各窝窦间的相互关系的影响情况进行了观察,并探讨了其临床意义。