Repair and Reconstruction of Peripheral Nerve Injuries. Treatment with G-CSF and Stromal Vascular Fraction.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1e4f154d-77a0-4827-919a-f279173e44a2
- author
- Frost, Hanna LU
- supervisor
-
- Lars Dahlin LU
- Per Ekström LU
- Per Fredrik Johansson LU
- 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
- 2019
- 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
- 2021-03-22 21:41:04
@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}},
}