title: Bone-marrow-derived mesenchymal stem cells promote proliferation and neuronal differentiation of Niemann-Pick type C mouse neural stem cells by upregulation and secretion of CCL2.
abstract: Niemann-Pick type C (NP-C) disease is a neurodegenerative disorder characterized neuropathologically by ballooned neurons distended with lipid storage and widespread neuronal loss. Neural stem cells (NSC) derived from NP-C disease models have decreased ability for self-renewal and neuronal differentiation. Investigation of neurogenesis in the adult brain has suggested that NP-C disease can be overcome, or at least ameliorated, by the generation of new neurons. Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are regarded as potential candidates for use in the treatment of neurodegenerative disorders because of their ability to promote neurogenesis. The underlying mechanisms of BM-MSC-induced promotion of neurogenesis, however, have not been resolved. The aim of the present study was to examine the mechanism of neurogenesis by BM-MSCs in NP-C disease. Coculture of embryonic NSCs from NP-C mice that exhibit impaired ability for self-renewal and decreased rates of neuronal differentiation with BM-MSCs resulted in an enhanced capacity for self-renewal and an increased ability for differentiation into neurons or oligodendrocytes. In addition, results of in vivo studies have demonstrated that transplantation of intracerebral BM-MSCs resulted in stimulated proliferation and neuronal differentiation of NSCs within the subventricular zone. Of particular interest, enhanced proliferation and neuronal differentiation of endogenous NP-C mouse NSCs showed an association with elevated release of the chemokine (C-C motif) ligand 2 (CCL2) from BM-MSCs. These effects suggest that soluble CCL2 derived from BM-MSCs can modulate endogenous NP-C NSCs, resulting in their improved proliferation and neuronal differentiation in mice.
authors: Stem Cell Neuroplasticity Research Group, Kyungpook National University, Daegu 702-701, South Korea.
authors: Hyun
authors: H
authors: Lee
authors: Ji Eun
authors: JE
authors: Kang
authors: Jong Kil
authors: JK
authors: Lee
authors: Jae-Sung
authors: JS
authors: Bae
authors: Hee Kyung
authors: HK
authors: Jin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D007150:Immunohistochemistry; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009500:Neutralization Tests; D052556:Niemann-Pick Disease, Type C / Q000628:therapy*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D045442:Rotarod Performance Test
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D017931:DNA Primers; D034741:RNA, Small Interfering; D001973:Bromodeoxyuridine
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