Convergence of human cellular models and genetics to study neural stem cell signaling to enhance central nervous system regeneration and repair

Publication date: Available online 16 August 2019Source: Seminars in Cell &Developmental BiologyAuthor(s): Dominic Julian, Ethan W. Hollingsworth, Katherine Julian, Jaime ImitolaAbstractHuman central nervous system (CNS) regeneration is considered the holy grail of neuroscience research, and is one of the most pressing and difficult questions in biology and science. Despite more than 20 years of work in the field of neural stem cells (NSCs), the area remains in its infancy as our understanding of the fundamental mechanisms that can be leveraged to improve CNS regeneration in neurological diseases is still growing. Here, we focus on the recent lessons from lower organism CNS regeneration genetics and how such findings are starting to illuminate our understanding of NSC signaling pathways in humans. These findings will allow us to improve upon our knowledge of endogenous NSC function, the utility of exogenous NSCs, and the limitations of NSCs as therapeutic vehicles for providing relief from devastating human neurological diseases. We also discuss the limitations of activating NSC signaling for CNS repair in humans, especially the potential for tumor formation. Finally, we will review the recent advances in new culture techniques, including patient-derived cells and cerebral organoids to model the genetic regulation of signaling pathways controlling the function of NSCs during injury and disease states.
Source: Seminars in Cell and Developmental Biology - Category: Cytology Source Type: research

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Publication date: Available online 12 September 2019Source: Stem Cell ReportsAuthor(s): Chen Feng, Wilson Cheuk Wing Chan, Yan Lam, Xue Wang, Peikai Chen, Ben Niu, Vivian Chor Wing Ng, Jia Chi Yeo, Sigmar Stricker, Kathryn Song Eng Cheah, Manuel Koch, Stefan Mundlos, Huck Hui Ng, Danny ChanSummaryThe synovial joint forms from a pool of progenitor cells in the future region of the joint, the interzone. Expression of Gdf5 and Wnt9a has been used to mark the earliest cellular processes in the formation of the interzone and the progenitor cells. However, lineage specification and progression toward the different tissues o...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research
For as long as I have been watching progress in tissue engineering, the primary and most important barrier to building organs to order has been the inability to construct vascular networks. A network of capillaries must exist for blood, and thus nutrients and oxygen necessary to cell survival, to reach more than a few millimeters into a tissue. In live tissues, hundreds of minuscule capillaries pass through every square millimeter, considered in cross-section. Replicating this level of capillary density in engineered tissue has yet to be accomplished, with even the more advanced technology demonstrations falling well short...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
Since the discovery of induced pluripotency more than a decade ago, researchers have been working towards the use of this technology to produce cells for use in tissue engineering and regenerative therapies. Induced pluripotent stem cells are functionally equivalent to embryonic stem cells; given suitable recipes and methods for the surrounding environment and signals, they can be made to generate any of the cell types in the body. The cornea of the eye is a comparatively simple starting point for tissue engineering, easier to work with in many ways, in generating tissues and in delivering cells to the patient. Here, the f...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
Abstract Diabetes mellitus increases the risk and accelerates the course of peripheral artery disease, making patients more susceptible to ischemic events and infections and delaying tissue healing. Current understanding of pathogenic mechanisms is mainly based on the negative influence of diabetes mellitus on atherosclerotic disease and inflammation. In recent years, the novel concept that diabetes mellitus can impinge on endogenous regenerative processes has been introduced. Diabetes mellitus affects regeneration at the local level, disturbing proper angiogenesis, collateral artery formation, and muscle repair. ...
Source: Arteriosclerosis, Thrombosis and Vascular Biology - Category: Cardiology Authors: Tags: Arterioscler Thromb Vasc Biol Source Type: research
In this study, we demonstrate for the first time the molecular events that contribute to osteogenic differentiation of PDLSCs. Dentin matrix protein 1 (DMP1) and its receptor, Glucose regulated protein-78 (GRP78), are localized in the progenitor cells of the PDL. Our overall goal is to demonstrate the formation of DMP1-GRP78 complex at the plasma membrane and subsequent protein trafficking and nuclear localization to promote osteogenic differentiation. To study the internalization and routing of the complex, we mimic an in vivo differentiation scenario by stimulating cells with DMP1 and culturing them in the presence of os...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
A new study, from the University of Toronto in Ontario, Canada, has found that the female sex hormone estradiol amplifies the effect that the drug metformin has on brain stem cells.
Source: the Mail online | Health - Category: Consumer Health News Source Type: news
Abstract Metals such as Ta (tantalum) and Ti (titanium) have been popularly used as a bone substitute or implants in orthopedic surgery and dentistry, since they have excellent corrosion. For manufacturing porous implants with precise structure, SLM (Selective laser melting), which is one of the 3D (three-dimensional) printing techniques, is always be chosen. To compare biological performances between porous Ta and Ti implants, we designed them with the same porosity, pore shape, pore size, and pore distribution via CAD (computer aided design), and then produced them by SLM. It was shown that the equivalent stress...
Source: Appl Human Sci - Category: Physiology Authors: Tags: Mater Sci Eng C Mater Biol Appl Source Type: research
In this study, we engineered different gelatin-based cryogels and studied the effect of nanohydroxyapatite (nHAP) and crosslinking agents on scaffold properties and its osteogenic response towards bone marrow stem cells (BMSCs). The cryogels examined are 5% gelatin and 5% gelatin/2.5% nHAP, crosslinked either with 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) or glutaraldehyde (GA). We confirmed that nHAP or the crosslinking agent has no effects on scaffold pore size and porosity. Nonetheless, incorporation of nHAP increased mechanical strength, swelling ratio and degree of crosslinking, but decreased degradation ra...
Source: Appl Human Sci - Category: Physiology Authors: Tags: Mater Sci Eng C Mater Biol Appl Source Type: research
In this study, SHED was first differentiated into ESCs and then effects of SHED and ESCs on wound closure were compared. Differentiation of SHED into ESCs was shown to induce growth factors that reached a maximum on the third day. In vivo, PFSM/ESC showed regeneration of granulation tissue on the third day, and the wound closure percent was 53.49%, which was 1.18-fold higher than PFSM/SHED. Therefore, the differentiation of stem cells into ESCs in advance combined with PFSM dressing can effectively accelerate wound healing in vivo. These findings can be applied to clinical treatment in the future. PMID: 31499995 [PubMed - in process]
Source: Appl Human Sci - Category: Physiology Authors: Tags: Mater Sci Eng C Mater Biol Appl Source Type: research
We present mSSC reliance on paracrine factors secreted by Schwann cells as the underlying mechanism, with partial rescue of the denervated phenotype by Schwann cell transplantation and by Schwann-derived growth factors. This work sheds light on the nerve dependency of mSSCs and has implications for clinical treatment of mandibular defects.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research
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