Transplanting Stem Cells into the Brain

2012 ◽  
pp. 529-542
Author(s):  
Mathew Blurton-Jones ◽  
Joy L. Nerhus ◽  
Frank M. LaFerla
Keyword(s):  
Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1468
Author(s):  
Yashika S. Kamte ◽  
Manisha N. Chandwani ◽  
Alexa C. Michaels ◽  
Lauren A. O’Donnell

Viruses that infect the central nervous system (CNS) are associated with developmental abnormalities as well as neuropsychiatric and degenerative conditions. Many of these viruses such as Zika virus (ZIKV), cytomegalovirus (CMV), and herpes simplex virus (HSV) demonstrate tropism for neural stem cells (NSCs). NSCs are the multipotent progenitor cells of the brain that have the ability to form neurons, astrocytes, and oligodendrocytes. Viral infections often alter the function of NSCs, with profound impacts on the growth and repair of the brain. There are a wide spectrum of effects on NSCs, which differ by the type of virus, the model system, the cell types studied, and the age of the host. Thus, it is a challenge to predict and define the consequences of interactions between viruses and NSCs. The purpose of this review is to dissect the mechanisms by which viruses can affect survival, proliferation, and differentiation of NSCs. This review also sheds light on the contribution of key antiviral cytokines in the impairment of NSC activity during a viral infection, revealing a complex interplay between NSCs, viruses, and the immune system.


Epigenomes ◽  
2018 ◽  
Vol 2 (3) ◽  
pp. 13
Author(s):  
José Belizário

Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.


2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Felipe de Almeida Sassi ◽  
Algemir Lunardi Brunetto ◽  
Gilberto Schwartsmann ◽  
Rafael Roesler ◽  
Ana Lucia Abujamra

Gliomas are the most incident brain tumor in adults. This malignancy has very low survival rates, even when combining radio- and chemotherapy. Among the gliomas, glioblastoma multiforme (GBM) is the most common and aggressive type, and patients frequently relapse or become refractory to conventional therapies. The fact that such an aggressive tumor can arise in such a carefully orchestrated organ, where cellular proliferation is barely needed to maintain its function, is a question that has intrigued scientists until very recently, when the discovery of the existence of proliferative cells in the brain overcame such challenges. Even so, the precise origin of gliomas still remains elusive. Thanks to new advents in molecular biology, researchers have been able to depict the first steps of glioma formation and to accumulate knowledge about how neural stem cells and its progenitors become gliomas. Indeed, GBM are composed of a very heterogeneous population of cells, which exhibit a plethora of tumorigenic properties, supporting the presence of cancer stem cells (CSCs) in these tumors. This paper provides a comprehensive analysis of how gliomas initiate and progress, taking into account the role of epigenetic modulation in the crosstalk of cancer cells with their environment.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuejiao Li ◽  
Yankai Dong ◽  
Ye Ran ◽  
Yanan Zhang ◽  
Boyao Wu ◽  
...  

Abstract Background We show previously that three-dimensional (3D) spheroid cultured mesenchymal stem cells (MSCs) exhibit reduced cell size thus devoid of lung entrapment following intravenous (IV) infusion. In this study, we determined the therapeutic effect of 3D-cultured MSCs on ischemic stroke and investigated the mechanisms involved. Methods Rats underwent middle cerebral artery occlusion (MCAO) and reperfusion. 1 × 106 of 3D- or 2D-cultured MSCs, which were pre-labeled with GFP, were injected through the tail vain three and seven days after MCAO. Two days after infusion, MSC engraftment into the ischemic brain tissues was assessed by histological analysis for GFP-expressing cells, and infarct volume was determined by MRI. Microglia in the lesion were sorted and subjected to gene expressional analysis by RNA-seq. Results We found that infusion of 3D-cultured MSCs significantly reduced the infarct volume of the brain with increased engraftment of the cells into the ischemic tissue, compared to 2D-cultured MSCs. Accordingly, in the brain lesion of 3D MSC-treated animals, there were significantly reduced numbers of amoeboid microglia and decreased levels of proinflammatory cytokines, indicating attenuated activation of the microglia. RNA-seq of microglia derived from the lesions suggested that 3D-cultured MSCs decreased the response of microglia to the ischemic insult. Interestingly, we observed a decreased expression of mincle, a damage-associated molecular patterns (DAMPs) receptor, which induces the production of proinflammatory cytokines, suggestive of a potential mechanism in 3D MSC-mediated enhanced repair to ischemic stroke. Conclusions Our data indicate that 3D-cultured MSCs exhibit enhanced repair to ischemic stroke, probably through a suppression to ischemia-induced microglial activation.


2010 ◽  
Vol 80 ◽  
pp. S33-S34
Author(s):  
J. Jeon ◽  
S. Cho ◽  
K. Cho ◽  
Y. Lee ◽  
M. Lee

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Da Yeon Lee ◽  
Sung Eun Lee ◽  
Do Hyeon Kwon ◽  
Saraswathy Nithiyanandam ◽  
Mi Ha Lee ◽  
...  

Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) have been studied for their application to manage various neurological diseases, owing to their anti-inflammatory, immunomodulatory, paracrine, and antiapoptotic ability, as well as their homing capacity to specific regions of brain injury. Among mesenchymal stem cells, such as BM-MSCs, adipose-derived MSCs, and umbilical cord MSCs, BM-MSCs have many merits as cell therapeutic agents based on their widespread availability and relatively easy attainability and in vitro handling. For stem cell-based therapy with BM-MSCs, it is essential to perform ex vivo expansion as low numbers of MSCs are obtained in bone marrow aspirates. Depending on timing, before hBM-MSC transplantation into patients, after detaching them from the culture dish, cell viability, deformability, cell size, and membrane fluidity are decreased, whereas reactive oxygen species generation, lipid peroxidation, and cytosolic vacuoles are increased. Thus, the quality and freshness of hBM-MSCs decrease over time after detachment from the culture dish. Especially, for neurological disease cell therapy, the deformability of BM-MSCs is particularly important in the brain for the development of microvessels. As studies on the traditional characteristics of hBM-MSCs before transplantation into the brain are very limited, omics and machine learning approaches are needed to evaluate cell conditions with indepth and comprehensive analyses. Here, we provide an overview of hBM-MSCs, the application of these cells to various neurological diseases, and improvements in their quality and freshness based on integrated omics after detachment from the culture dish for successful cell therapy.


Author(s):  
Sebastian Jessberger ◽  
Armin Curt ◽  
Roger A. Barker

A number of diseases of the brain and spinal cord are associated with substantial neural cell death and/or disruption of correct and functional neural networks. In the past, a variety of therapeutic strategies to rescue these systems have been proposed along with agents to induce functional plasticity within the remaining central nervous system (CNS) structures. In the case of injury or neurodegenerative disease these approaches have only met with limited success, indicating the need for novel approaches to treat diseases of the adult CNS. Recently, the idea of recruiting endogenous or transplanting stem cells to replace lost structures within the adult brain or spinal cord has gained significant attention, along with in situ reprogramming, and opened up novel therapeutic avenues in the context of regenerative medicine. Here we review recent advances in our understanding of how endogenous stem cells may be a part of pathological processes in certain neuropsychiatric diseases and summarize recent clinical and preclinical data suggesting that stem cell-based therapies hold great promise as a future treatment option in a number of diseases disrupting the proper function of the adult CNS.


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