PMID- 18575624
OWN - NLM
STAT- MEDLINE
DCOM- 20080820
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 3
IP  - 6
DP  - 2008 Jun 25
TI  - TSP-1 secreted by bone marrow stromal cells contributes to retinal ganglion cell 
      neurite outgrowth and survival.
PG  - e2470
LID - 10.1371/journal.pone.0002470 [doi]
LID - e2470
AB  - 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.
FAU - Yu, Keming
AU  - Yu K
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, People's Republic of China.
FAU - Ge, Jian
AU  - Ge J
FAU - Summers, James Bradley
AU  - Summers JB
FAU - Li, Fan
AU  - Li F
FAU - Liu, Xuan
AU  - Liu X
FAU - Ma, Ping
AU  - Ma P
FAU - Kaminski, Joseph
AU  - Kaminski J
FAU - Zhuang, Jing
AU  - Zhuang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080625
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (DNA Primers)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Synaptophysin)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells/*metabolism
MH  - *Cell Survival
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - DNA Primers
MH  - Down-Regulation
MH  - Female
MH  - Gene Silencing
MH  - Microtubule-Associated Proteins/genetics
MH  - Polymerase Chain Reaction
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retinal Ganglion Cells/*cytology
MH  - Stromal Cells/*metabolism
MH  - Synaptophysin/genetics
MH  - Thrombospondin 1/genetics/*metabolism
MH  - Transforming Growth Factor beta/genetics
PMC - PMC2430538
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2008/06/26 09:00
MHDA- 2008/08/21 09:00
PMCR- 2008/06/25
CRDT- 2008/06/26 09:00
PHST- 2007/08/27 00:00 [received]
PHST- 2008/05/16 00:00 [accepted]
PHST- 2008/06/26 09:00 [pubmed]
PHST- 2008/08/21 09:00 [medline]
PHST- 2008/06/26 09:00 [entrez]
PHST- 2008/06/25 00:00 [pmc-release]
AID - 07-PONE-RA-02542R3 [pii]
AID - 10.1371/journal.pone.0002470 [doi]
PST - epublish
SO  - PLoS One. 2008 Jun 25;3(6):e2470. doi: 10.1371/journal.pone.0002470.