Embryonic Stem Cell in the Therapy of Neurodegenerative Diseases
Year: 2011
Type: book-chapter
Abstract: and Drug Administration (FDA) in January 2009.It seemed that hESCs could be expected as a potential future cell source for cell therapy in neurodegenerative disease.AD and PD are the most prevalent kinds of neurodegenerative diseases in ageing people.Although not so prevalent, HD and ALS are devasting motor neuron degenerative diseases, the patients usually died of this disease shortly after diagnosis (Roze et al., 2010;Perry et al., 2010).These neurodegenerative diseases share many important commonalities, characterized by neuron loss as structural feature.Meanwhile, a different spectrum of cell types is affected in these diseases.Therefore, different types of neurons are required for replacement (Srivastava et al., 2008).When stem cell transplantation used in these diseases, the strategies will vary according to the primary defect of a disease.As above-mentioned, ESCs are promising cell source for cell therapy in neurodegenerative disease, recent progress of ESCs-based therapies in these diseases is discussed below. Embryonic stem cell biology 2.1 Cellular and molecular characteristics of embryonic stem cellESCs were independently first derived from mouse embryos by Martin Evans and Mattew kaufman in 1981 (Evans & Kaufman, 1981).This is also the first time to reveal a new technique for culturing the mouse embryos in the uterus to allow for an increase in cell number, which has been further confirmed by Martin (Martin et al., 1987).In 1998, James Thomson firstly developed a technique to isolate and grow hESCs in cell culture (Thomson et al., 1998).Later, ESCs have been isolated from other species, including swine, simian, monkeys and human blastocysts, but only three species of mammals have yielded long-term cultures of self-renewing ESCs namely mice, monkeys and humans (Ohtsuka & Dalton, 2008).Both mouse and human ESCs have the properties of self-renewal and the potential to be committed and differentiated in vitro into all three germ layers-namely, ectoderm, endoderm, and mesoderm (Murry & Keller, 2008).Both stem cell populations express the characteristic markers of undifferentiated cells, including Oct-4(octamer binding transcription factor-4), nanog, Sox-2(SRY-related HMG box 2) and utf-1, together with the lack of differentiation markers (Sauerzweig et al., 2009).They also express stage-specific embryonic antigen-3 and -4 (SSEA-3 and -4), tumor-rejection antigen-1-60 and -1-81, and high levels of telomerase activity (Murry & Keller, 2008).ESCs cultures from mouse and human are similar in that they grow as colonies of tightly packed cells on inactivated murine embryonic fibroblast(MEF) feeders or in conditioned medium(CM) derived from such MEFs (Li et al., 2005).The mechanisms by which ESCs from different species maintain self-renewal and pluripotency are still not yet fully understood.It seemed that they have different mechanisms.Maintenance of mouse ESCs pluripotency in vitro is achieved by coculture on irradiated mouse fibroblasts or on gelatinized dishes with a differentiation inhibitory factor called leukemia inhibitory factor(LIF) (Cheng et al., 2003).In addition to LIF, bone morphogenetic protein 4(BMP4) and the secreted wnt proteins may also contribute to maintain ESCs pluripotency (Hiller et al., 2010).Other factors such as Sox2, FoxD3 (forkhead box D3) and Nanog can also maintain self-renewal of mouse ESCs.Human ESCs pluripotency is regulated by a combination of extrinsic and intrinsic factors.Unlike mouse, extrinsic factors such as fibroblast growth factor(FGF) signaling and a balance between transforming growth factor-(TGF-)/activin and BMP signaling are central to the self-renewal of human ESCs (Xu et al., 2008).Intrinsic factors regulating
Source: InTech eBooks
DOI: 10.5772/14119
Authors: Xiaotang Fan, Yongping Tang, Kai Wang, Xiang Cui, Shiqi Tao, Haiwei Xu
Institutions: Army Medical University, Southwest Hospital, University of Houston
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W1593182943