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OPEN ACCESS PLUS
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Contents
4(4): Pp. 266 - 280
Sabrina Mattoli, Alberto Bellini and Matthias Schmidt
[Open Access Plus] |
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The human peripheral blood contains a multipotent precursor that shows hematopoietic stem cell features and transiently expresses markers of the myeloid lineage. Under permissive conditions, this precursor gives rise to committed progenitors of various lineages, including a mesenchymal progenitor cell known by the name of fibrocyte. The fibrocytes still express some hematopoietic and myeloid antigens together with fibroblast markers. They constitutively release profibrotic and angiogenic factors and can modulate ongoing inflammatory reactions through the release of a number of chemokines. Under appropriate stimulation, fibrocytes produce increased amounts of extracellular matrix components and acquire a contractile phenotype similar to that of activated fibroblasts (myofibroblasts). Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in pulmonary diseases characterized by an extensive remodeling of the bronchial wall or progressive fibrosis, in the skin of patients affected by nephrogenic systemic fibrosis, in human hypertrophic scars, in proliferative vitreoretinopathies and atherosclerotic lesions. Similar cells also participate in the stromal reaction to tumor development. Prevention of detrimental tissue remodeling in fibrotic diseases may be achieved by inhibiting the accumulation of fibrocytes. In-vitro expanded fibrocytes may be used to improve ineffective tissue repair or may be engineered for the delivery of gene constructs in anti-cancer therapy.
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4(2): Pp. 118 - 130
Morgane Locker, Caroline Borday and Muriel Perron
[Open Access Plus] |
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Many retinal dystrophies are associated with photoreceptor loss, which causes irreversible blindness. The recent identification of various sources of stem cells in the mammalian retina has raised the possibility that cell-based therapies might be efficient strategies to treat a wide range of incurable eye diseases. A first step towards the successful therapeutic exploitation of these cells is to unravel intrinsic and extrinsic regulators that control their proliferation and cell lineage determination. In this review, we provide an overview of the different types and molecular fingerprints of retinal stem cells identified so far. We also detail the current knowledge on molecular cues that influence their self-renewal and proliferation capacity. In particular, we focus on recent data implicating developmental signaling pathways, such as Wnt, Notch and Hedeghog, both in the normal and regenerating retina in different animal models. Last, we discuss the potential of ES cells and various adult stem cells for retinal repair.
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3(4): Pp. 288 - 302
Kohzo Nakayama, Hisashi Nagase, Masahiro Hiratochi, Chang-Sung Koh and Takeshi Ohkawara
[Open Access Plus] |
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In the canonical Notch signaling pathway, intramembrane cleavage by γ-secretase serves to release an intracellular domain of Notch that has activity in the nucleus through binding to transcription factors. In addition, we showed that Notch also supplies signals to Delta, a major Notch ligand, to release the intracellular domain of Delta by γ-secretase from the cell membrane, which then translocates to the nucleus, where it mediates the transcription of specific genes. Therefore, the Notch-Delta signaling pathway is bi-directional and similar mechanisms regulated by γ-secretase are involved in both directions. Recently, it was demonstrated that many type 1 transmembrane proteins including Notch, Delta and amyloid precursor protein (APP) are substrates for γ-secretase and release intracellular domains of these proteins from cell membranes. These observations that the common enzyme, γ-secretase, modulates proteolysis and the turnover of possible signaling molecules have led to the attractive hypothesis that mechanisms similar to the Notch-Delta signaling pathway may widely contribute to γ-secretase-regulated signaling pathways, including APP signaling which leads to Alzheimers disease. Here, we review the molecular mechanisms of the Notch-Delta signaling pathway in a bi-directional manner, and discuss the recent progress in understanding the biology of γ-secretase-regulated signaling with respect to neurodegeneration.
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3(2): Pp. 99 - 106
William G. Kerr
[Open Access Plus] |
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Inositol phospholipid signaling pathways have begun to emerge as important players in stem cell biology and bone marrow transplantation [1-4]. The SH2-containing Inositol Phosphatase (SHIP) is among the enzymes that can modify endogenous mammalian phosphoinositides. SHIP encodes an isoform specific to pluripotent stem (PS) cells [5,6] plays a role in hematopoietic stem (HS) cell biology [7,8] and allogeneic bone marrow (BM) transplantation [1,2,9,10]. Here I discuss our current understanding of the cell and molecular pathways that SHIP regulates that influence PS/HS cell biology and BM transplantation. Genetic models of SHIP-deficiency indicate this enzyme is a potential molecular target to enhance both autologous and allogeneic BM transplantation. Thus, strategies to reversibly target SHIP expression and their potential application to stem cell therapies and allogeneic BMT are also discussed.
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1(3): Pp. 325 - 331
Ilham Saleh Abuljadayel
[Open Access Plus] |
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Processes involving conversion of mature adult cells into undifferentiated cells have tremendous therapeutic potential in treating a variety of malignant and non-malignant disorders, including degenerative diseases. This can be achieved in autologous or allogeneic settings, by replacing either defective cells or regenerating those that are in deficit through reprogramming more commited cells into stem cells. The concept behind reprogramming differentiated cells to a stem cell state is to enable the switching of development towards the required cell lineage that is capable of correcting the underlying cellular dysfunction. The techniques by which differentiated cells can reverse their development, become pluripotent stem cells and transdifferentiate to give rise to new tissue or an entire organism are currently under intense investigation. Examples of reprogramming differentiation in mature adult cells include nuclear reprogramming of more commited cells using the cytoplasm of empty oocytes obtained from a variety of animal species, or cell surface contact of differentiated cells through receptor ligand interaction. Such ligands include monoclonal antibodies, cytokines or synthetic chemical compounds. Despite controversies surrounding such techniques, the concept behind identification and design/screening of biological or pharmacological compounds to enable re-switching of cell fate in-vivo or ex-vivo is paramount for current drug therapies to be able to target more specifically cellular dysfunction at the tissue/organ level. Herein, this review discusses current research in cellular reprogramming and its potential application in regenerative medicine.
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