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Biphasic Electrical Targeting Plays a Significant Role in Schwann Cell Activation.
MedLine Citation:
PMID:  21235401     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Electrical stimulation (ES) is a promising technique for axonal regeneration of peripheral nerve injuries. However, long-term, continuous ES in the form of biphasic electric current (BEC) to stimulate axonal regeneration has rarely been attempted and the effects of BEC on Schwann cells are unknown. We hypothesized that long-term, continuous ES would trigger the activation of Schwann cells, and we therefore investigated the effect of BEC on the functional differentiation of primary human mesenchymal stromal cells (hMSCs) into Schwann cells, as well as the activity of primary Schwann cells. Differentiation of hMSCs into Schwann cells was determined by co-culture with rat pheochromocytoma cells (PC12 cell line). We also investigated the in vivo effects of long-term ES (4 weeks) on axonal outgrowth of a severed sciatic nerve with a 7-mm gap following retraction of the nerve ends in rats by implanting an electronic device to serve as a neural conduit. PC12 cells co-cultured with hMSCs electrically-stimulated during culture in Schwann cell differentiation medium (Group I) had longer neurites and a greater percentage of PC12 cells were neurite-sprouting than when co-cultured with hMSCs cultured in growth medium (Control Group) or unstimulated hMSCs in the same culture conditions as used for Group I (Group II). Group I cells showed significant upregulation of Schwann cell-related neurotrophic factors such as nerve growth factor (NGF) and glial-derived neurotrophic factor (GDNF) compared to Group II cells at both the mRNA and protein levels. Primary Schwann cells responded to continuous BEC with increased proliferation and the induction of NGF and GDNF, similar to Group I cells, and in addition, induction of brain-derived neurotrophic factor was observed. Immunohistochemical investigation of sciatic nerve regenerates revealed that BEC increased axonal outgrowth significantly. These results demonstrate that BEC enhanced the functional activity of Schwann cells via the induction of neurotrophic factor release and guide-increased axonal outgrowth in vivo. The effectiveness of long term ES highlights the feasibility of a BEC-based therapeutic device to accelerate nerve regeneration of severed peripheral nerve injuries with a gap.
Authors:
In Sook Kim; Yun Mi Song; Tae Hyung Cho; Hui Pan; Tae Hyung Lee; Sung June Kim; Soon Jung Hwang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-1-15
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  -     ISSN:  1937-335X     ISO Abbreviation:  -     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Seoul National University, Dental Research Institute, Seoul, Korea, Republic of; ishwkim@snu.ac.kr.
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