TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.

Hdl Handle:
http://hdl.handle.net/10675.2/145
Title:
TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.
Authors:
Yu, Keming; Ge, Jian; Summers, James Bradley; Li, Fan; Liu, Xuan; Ma, Ping; Kaminski, Joseph; Zhuang, Jing
Abstract:
BACKGROUND: Bone marrow stromal cells (BMSCs) are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs) model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1), as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR) was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA) transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important role in neural-like differentiation in BMSCs and neurite outgrowth in RGCs. This study provides new insights into the potential reparative mechanisms of neural cell repair.
Citation:
PLoS ONE. 2008 Jun 25; 3(6):e2470
Issue Date:
25-Jun-2008
URI:
http://hdl.handle.net/10675.2/145
DOI:
10.1371/journal.pone.0002470
PubMed ID:
18575624
PubMed Central ID:
PMC2430538
Type:
Journal Article; Research Support, Non-U.S. Gov't
ISSN:
1932-6203
Appears in Collections:
Department of Radiology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorYu, Kemingen_US
dc.contributor.authorGe, Jianen_US
dc.contributor.authorSummers, James Bradleyen_US
dc.contributor.authorLi, Fanen_US
dc.contributor.authorLiu, Xuanen_US
dc.contributor.authorMa, Pingen_US
dc.contributor.authorKaminski, Josephen_US
dc.contributor.authorZhuang, Jingen_US
dc.date.accessioned2010-09-24T22:03:27Z-
dc.date.available2010-09-24T22:03:27Z-
dc.date.issued2008-06-25en_US
dc.identifier.citationPLoS ONE. 2008 Jun 25; 3(6):e2470en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid18575624en_US
dc.identifier.doi10.1371/journal.pone.0002470en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/145-
dc.description.abstractBACKGROUND: Bone marrow stromal cells (BMSCs) are pluripotent and thereby a potential candidate for cell replacement therapy for central nervous system degenerative disorders and traumatic injury. However, the mechanism of their differentiation and effect on neural tissues has not been fully elucidated. This study evaluates the effect of BMSCs on neural cell growth and survival in a retinal ganglion cell (RGCs) model by assessing the effect of changes in the expression of a BMSC-secreted protein, thrombospondin-1 (TSP-1), as a putative mechanistic agent acting on RGCs. METHODS AND FINDINGS: The effect of co-culturing BMSCs and RGCs in vitro was evaluated by measuring the following parameters: neurite outgrowth, RGC survival, BMSC neural-like differentiation, and the effect of TSP-1 on both cell lines under basal secretion conditions and when TSP-1 expression was inhibited. Our data show that BMSCs improved RGC survival and neurite outgrowth. Synaptophysin, MAP-2, and TGF-beta expression are up-regulated in RGCs co-cultured with BMSCs. Interestingly, the BMSCs progressively displayed neural-like morphology over the seven-day study period. Restriction display polymerase chain reaction (RD-PCR) was performed to screen for differentially expressed genes in BMSCs cultured alone or co-cultured with RGCs. TSP-1, a multifactorial extracellular matrix protein, is critically important in the formation of neural connections during development, so its function in our co-culture model was investigated by small interfering RNA (siRNA) transfection. When TSP-1 expression was decreased with siRNA silencing, BMSCs had no impact on RGC survival, but reduced neurite outgrowth and decreased expression of synaptophysin, MAP-2 and TGF-beta in RGCs. Furthermore, the number of BMSCs with neural-like characteristics was significantly decreased by more than two-fold using siRNA silencing. CONCLUSIONS: Our data suggest that the TSP-1 signaling pathway might have an important role in neural-like differentiation in BMSCs and neurite outgrowth in RGCs. This study provides new insights into the potential reparative mechanisms of neural cell repair.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBone Marrow Cells / secretionen_US
dc.subject.meshCell Survivalen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCoculture Techniquesen_US
dc.subject.meshDNA Primersen_US
dc.subject.meshDown-Regulationen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Silencingen_US
dc.subject.meshMicrotubule-Associated Proteins / geneticsen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshRNA Interferenceen_US
dc.subject.meshRNA, Small Interfering / geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshRetinal Ganglion Cells / cytologyen_US
dc.subject.meshStromal Cells / secretionen_US
dc.subject.meshSynaptophysin / geneticsen_US
dc.subject.meshThrombospondin 1 / genetics / secretionen_US
dc.subject.meshTransforming Growth Factor beta / geneticsen_US
dc.titleTSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2430538en_US
dc.contributor.corporatenameDepartment of Radiologyen_US

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