Abstract
Background
Several studies have examined the enhanced efficacy of mesenchymal stem cells (MSCs)
using neurotrophic factor transfection in ischemic rat models. However, gene therapy,
e.g., the application of MSCs transfected with neurotrophic factors, is not feasible in
clinical practice for ethical reasons. Therefore, we evaluated cultivation with specific
trophic factors in an attempt to enhance the efficacy of human MSCs (hMSCs) in ischemic
stroke.
Methods
Using quantitative sandwich enzyme-linked immunosorbent assay (ELISA), we analyzed
the levels of trophic factors released from hMSCs after treatment with ischemic brain
extract. Trophic factors were pretreated under ex vivo culture conditions. The concentrations of each trophic factor produced by the trophic
factor-pretreated and non-pretreated hMSCs were then measured and compared.
Results
hMSCs cultured with ischemic rat brain extract showed increased production of BDNF
(brain-derived neurotrophic factor), VEGF (vascular endothelial growth factor) and
HGF (hepatocyte growth factor). Ex vivo treatment with trophic factors led to a further increase in the production of the
trophic factor by hMSC, suggesting autocrine regulation of hMSCs. The morphology and
expression of surface markers of hMSCs were not changed, but the cell viability and
cell proliferation ability increased after treatment with trophic factors.
Conclusions
Our data indicate that hMSCs provide trophic support to the ischemic brain, which
can be enhanced by ex vivo treatment of trophic factors during cultivation of hMSCs.
Keywords
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Article info
Publication history
Accepted:
September 1,
2010
Received in revised form:
August 18,
2010
Received:
November 26,
2009
Identification
Copyright
© 2010 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
