Recruitment by SDF-1α of CD34-positive cells involved in sciatic nerve regeneration

Laboratory investigation

Meei-Ling Sheu Institutes of Biomedical Sciences and

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 Ph.D.
,
Fu-Chou Cheng Stem Cell Center, Taichung Veterans General Hospital, Taichung;
Education and Medical Research, and

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 Ph.D.
,
Hong-Lin Su Life Sciences, National Chung-Hsing University;

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 Ph.D.
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Ying-Ju Chen Stem Cell Center, Taichung Veterans General Hospital, Taichung;

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 Ph.D.
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Chun-Jung Chen Education and Medical Research, and

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 Ph.D.
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Chih-Ming Chiang Radiology, and

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 M.S.
,
Wen-Ta Chiu Department of Neurosurgery, Taipei Medical University–Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan; and

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 M.D., Ph.D.
,
Jason Sheehan Department of Neurosurgery, University of Virginia Health System, Charlottesville, Virginia

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 M.D., Ph.D.
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Hung-Chuan Pan Institutes of Biomedical Sciences and
Departments of Neurosurgery,

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 M.D., Ph.D.
Page Range:
432–444
Volume/Issue:
Volume 116: Issue 2
DOI link:
https://doi.org/10.3171/2011.3.JNS101582
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Object

Increased integration of CD34+ cells in injured nerve significantly promotes nerve regeneration, but this effect can be counteracted by limited migration and short survival of CD34+ cells. SDF-1α and its receptor mediate the recruitment of CD34+ cells involved in the repair mechanism of several neurological diseases. In this study, the authors investigate the potentiation of CD34+ cell recruitment triggered by SDF-1α and the involvement of CD34+ cells in peripheral nerve regeneration.

Methods

Peripheral nerve injury was induced in 147 Sprague-Dawley rats by crushing the left sciatic nerve with a vessel clamp. The animals were allocated to 3 groups: Group 1, crush injury (controls); Group 2, crush injury and local application of SDF-1α recombinant proteins; and Group 3, crush injury and local application of SDF-1α antibody. Electrophysiological studies and assessment of regeneration markers were conducted at 4 weeks after injury; neurobehavioral studies were conducted at 1, 2, 3, and 4 weeks after injury. The expression of SDF-1α, accumulation of CD34+ cells, immune cells, and angiogenesis factors in injured nerves were evaluated at 1, 3, 7, 10, 14, 21, and 28 days after injury.

Results

Application of SDF-1α increased the migration of CD34+ cells in vitro, and this effect was dose dependent. Crush injury induced the expression of SDF-1α, with a peak of 10–14 days postinjury, and this increased expression of SDF-1α paralleled the deposition of CD34+ cells, expression of VEGF, and expression of neurofilament. These effects were further enhanced by the administration of SDF-1α recombinant protein and abolished by administration of SDF-1α antibody. Furthermore, these effects were consistent with improvement in measures of neurological function such as sciatic function index, electrophysiological parameters, muscle weight, and myelination of regenerative nerve.

Conclusions

Expression of SDF-1α facilitates recruitment of CD34+ cells in peripheral nerve injury. The increased deposition of CD34+ cells paralleled significant expression of angiogenesis factors and was consistent with improvement of neurological function. Utilization of SDF-1α for enhancing the recruitment of CD34+ cells involved in peripheral nerve regeneration may be considered as an alternative treatment strategy in peripheral nerve disorders.

Abbreviations used in this paper:

CMAP = compound muscle action potential; ECM = extracellular matrix; G-CSF = granulocyte colony-stimulating factor; HPC = hematopoietic progenitor cell; RI = regularity index; SFI = sciatic function index.
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Contributor Notes

Address correspondence to: Hung-Chuan Pan, M.D., Ph.D., Department of Neurosurgery, Taichung Veterans General Hospital, No. 160, Taichung-Kang Road, Section 3, Taichung 407, Taiwan. email: hcpan2003@yahoo.com.tw.

Please include this information when citing this paper: published online August 19, 2011; DOI: 10.3171/2011.3.JNS101582.

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