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Repair and Reconstruction of Peripheral Nerve Injuries. Treatment with G-CSF and Stromal Vascular Fraction.

Frost, Hanna LU (2019) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2019(97).
Abstract (Swedish)
While surgery is a cornerstone in treatment of peripheral nerve injuries, it is not a comprehensive approach, and outcome is unsatisfactory, especially sensory function. The present aim was to translate recent findings about stem- and progenitor cells to improve regenerative outcome, where the cells have to be autologous, available within the same surgical procedure, and minimally manipulated.

Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic stem cells from the bone marrow. Post-traumatic G-CSF therapy, evaluated in a rat sciatic nerve injurymodel with immediate repair, showed a 13% local decrease in Schwann cell apoptosis at the site of lesion, and a similar trend in the distal nerve segment in healthy rats,... (More)
While surgery is a cornerstone in treatment of peripheral nerve injuries, it is not a comprehensive approach, and outcome is unsatisfactory, especially sensory function. The present aim was to translate recent findings about stem- and progenitor cells to improve regenerative outcome, where the cells have to be autologous, available within the same surgical procedure, and minimally manipulated.

Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic stem cells from the bone marrow. Post-traumatic G-CSF therapy, evaluated in a rat sciatic nerve injurymodel with immediate repair, showed a 13% local decrease in Schwann cell apoptosis at the site of lesion, and a similar trend in the distal nerve segment in healthy rats, and at the site of lesion in diabetic Goto-Kakizaki rats. G-CSF had no effect on axonal outgrowth in short- or long term experiments.

Stromal vascular fraction (SVF) of adipose tissue is a heterogenic mixture of cells, including small amounts of adipose derived stem cells. Electrospun multi-channeled nerve conduits, designed to mimic a native nerve, with longitudinal nanofibers inside the channels for axonal guidance +/- delivered SVF to the nerve conduit was used to bridge a 10 mm sciatic nerve gap in healthy rats. The nerve conduit supported axonal outgrowth and acted as a cell delivery vehicle during the observation time (four weeks). SVF did not improve axonal outgrowth, and adverse effects – gross encapsulation – was observed in 9/30 implants after SVF therapy. Schwann cell infiltration was inferior in nerve conduits supplemented with SVF cells, with a partially enhanced inflammatory response.

Co-culture of SVF cells and peripheral nerve segments performed on aligned nanofibers, recreating in vitro the environment above, showed no change in expression of Schwann cell marker S-100 in SVF cells, but increased Sox10 in SVF cells exposed to a nerve segment compared to baseline. Pilot experiments with mass spectrometry indicated a SVF-nerve interplay in the local microenvironment.

In conclusion, G-CSF and SVF therapy affected glial cells, but did not improve axonal outgrowth. G-CSF decreases Schwann cell apoptosis, but does not improve regenerative outcome. An electrospun nerve conduit can be used to bridge a nerve gap and act as a cell delivery vehicle. SVF delivered in micro-channels interferes with ingrowth of Schwann cells by unknown mechanisms. (Less)
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author
supervisor
opponent
  • Universität-Professor Radtke, Christine, Medical University of Vienna, Vienna, Austria
organization
alternative title
Reparation och rekonstruktion av perifera nervskador : Behandling med G-CSF och stromal vascular fraction
publishing date
type
Thesis
publication status
published
subject
keywords
peripheral nerve injuries, nerve regeneration, reconstructive surgical procedures, diabetes mellitus, rat sciatic nerve, granulocyte colony-stimulating factor, stromal vascular fraction, electrospinning, rats, Schwann cells
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2019
issue
97
pages
76 pages
publisher
Lund University: Faculty of Medicine
defense location
Lilla aulan, Jan Waldenströms gata 5, Skånes Universitetssjukhus i Malmö
defense date
2019-11-08 09:00:00
ISSN
1652-8220
ISBN
978-91-7619-826-1
language
English
LU publication?
yes
id
1e4f154d-77a0-4827-919a-f279173e44a2
date added to LUP
2019-10-18 10:13:32
date last changed
2019-11-19 13:49:52
@phdthesis{1e4f154d-77a0-4827-919a-f279173e44a2,
  abstract     = {While surgery is a cornerstone in treatment of peripheral nerve injuries, it is not a comprehensive approach, and outcome is unsatisfactory, especially sensory function. The present aim was to translate recent findings about stem- and progenitor cells to improve regenerative outcome, where the cells have to be autologous, available within the same surgical procedure, and minimally manipulated. <br/><br/>Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic stem cells from the bone marrow. Post-traumatic G-CSF therapy, evaluated in a rat sciatic nerve injurymodel with immediate repair, showed a 13% local decrease in Schwann cell apoptosis at the site of lesion, and a similar trend in the distal nerve segment in healthy rats, and at the site of lesion in diabetic Goto-Kakizaki rats. G-CSF had no effect on axonal outgrowth in short- or long term experiments.<br/><br/>Stromal vascular fraction (SVF) of adipose tissue is a heterogenic mixture of cells, including small amounts of adipose derived stem cells. Electrospun multi-channeled nerve conduits, designed to mimic a native nerve, with longitudinal nanofibers inside the channels for axonal guidance +/- delivered SVF to the nerve conduit was used to bridge a 10 mm sciatic nerve gap in healthy rats. The nerve conduit supported axonal outgrowth and acted as a cell delivery vehicle during the observation time (four weeks). SVF did not improve axonal outgrowth, and adverse effects – gross encapsulation – was observed in 9/30 implants after SVF therapy. Schwann cell infiltration was inferior in nerve conduits supplemented with SVF cells, with a partially enhanced inflammatory response.<br/><br/>Co-culture of SVF cells and peripheral nerve segments performed on aligned nanofibers, recreating in vitro the environment above, showed no change in expression of Schwann cell marker S-100 in SVF cells, but increased Sox10 in SVF cells exposed to a nerve segment compared to baseline. Pilot experiments with mass spectrometry indicated a SVF-nerve interplay in the local microenvironment.<br/><br/>In conclusion, G-CSF and SVF therapy affected glial cells, but did not improve axonal outgrowth. G-CSF decreases Schwann cell apoptosis, but does not improve regenerative outcome. An electrospun nerve conduit can be used to bridge a nerve gap and act as a cell delivery vehicle. SVF delivered in micro-channels interferes with ingrowth of Schwann cells by unknown mechanisms.},
  author       = {Frost, Hanna},
  isbn         = {978-91-7619-826-1},
  issn         = {1652-8220},
  language     = {eng},
  number       = {97},
  publisher    = {Lund University: Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Repair and Reconstruction of Peripheral Nerve Injuries. Treatment with G-CSF and Stromal Vascular Fraction.},
  url          = {https://lup.lub.lu.se/search/ws/files/70767769/Hanna_Frost_Thesis_minus_appendix.pdf},
  volume       = {2019},
  year         = {2019},
}