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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
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
project
Repair and Reconstruction of Peripheral Nerve Injuries: Treatment with G-CSF and Stromal Vascular Fraction
language
English
LU publication?
yes
id
1e4f154d-77a0-4827-919a-f279173e44a2
date added to LUP
2019-10-18 10:13:32
date last changed
2025-10-21 13:05:09
@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}},
  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}},
  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/files/70767769/Hanna_Frost_Thesis_minus_appendix.pdf}},
  volume       = {{2019}},
  year         = {{2019}},
}