TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell neurite outgrowth and survival.
Summers, James Bradley
MetadataShow full item record
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.
CitationPLoS ONE. 2008 Jun 25; 3(6):e2470
- Characterization of conditioned medium of cultured bone marrow stromal cells.
- Authors: Nakano N, Nakai Y, Seo TB, Yamada Y, Ohno T, Yamanaka A, Nagai Y, Fukushima M, Suzuki Y, Nakatani T, Ide C
- Issue date: 2010 Oct 8
- Bone morphogenetic proteins promote neurite outgrowth in retinal ganglion cells.
- Authors: Kerrison JB, Lewis RN, Otteson DC, Zack DJ
- Issue date: 2005 Mar 18
- Effects of optineurin siRNA on apoptotic genes and apoptosis in RGC-5 cells.
- Authors: Li H, Ao X, Jia J, Wang Q, Zhang Z
- Issue date: 2011
- Molecular and cellular reactions of retinal ganglion cells and retinal glial cells under centrifugal force loading.
- Authors: Kashiwagi K, Iizuka Y, Tanaka Y, Araie M, Suzuki Y, Tsukahara S
- Issue date: 2004 Oct
- Lentiviral-mediated growth-associated protein-43 modification of bone marrow mesenchymal stem cells improves traumatic optic neuropathy in rats.
- Authors: Zhu Q, Liu Z, Wang C, Nie L, He Y, Zhang Y, Liu X, Su G
- Issue date: 2015 Oct