Schol, Jordy; Sakai, Daisuke; Warita, Takayuki; Nukaga, Tadashi; Sako, Kosuke; Wangler, Sebastian; Tamagawa, Shota; Zeiter, Stephan; Alini, Mauro; Grad, Sibylle (2022). Homing of vertebral-delivered mesenchymal stromal cells for degenerative intervertebral discs repair - an in vivo proof-of-concept study. JOR Spine, 6(1), e1228. Wiley 10.1002/jsp2.1228
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INTRODUCTION
Cell transplantation shows promising results for intervertebral disc (IVD) repair, however, contemporary strategies present concerns regarding needle puncture damage, cell retention, and straining the limited nutrient availability. Mesenchymal stromal cell (MSC) homing is a natural mechanism of long-distance cellular migration to sites of damage and regeneration. Previous ex vivo studies have confirmed the potential of MSC to migrate over the endplate and enhance IVD-matrix production. In this study, we aimed to exploit this mechanism to engender IVD repair in a rat disc degeneration model.
METHODS
Female Sprague Dawley rats were subjected to coccygeal disc degeneration through nucleus pulposus (NP) aspiration. In part 1; MSC or saline was transplanted into the vertebrae neighboring healthy or degenerative IVD subjected to irradiation or left untouched, and the ability to maintain the IVD integrity for 2 and 4 weeks was assessed by disc height index (DHI) and histology. For part 2, ubiquitously GFP expressing MSC were transplanted either intradiscally or vertebrally, and regenerative outcomes were compared at days 1, 5, and 14 post-transplantation. Moreover, the homing potential from vertebrae to IVD of the GFP+ MSC was assessed through cryosection mediated immunohistochemistry.
RESULTS
Part 1 of the study revealed significantly improved maintenance of DHI for IVD vertebrally receiving MSC. Moreover, histological observations revealed a trend of IVD integrity maintenance. Part 2 of the study highlighted the enhanced DHI and matrix integrity for discs receiving MSC vertebrally compared with intradiscal injection. Moreover, GFP rates highlighted MSC migration and integration in the IVD at similar rates as the intradiscally treated cohort.
CONCLUSION
Vertebrally transplanted MSC had a beneficial effect on the degenerative cascade in their neighboring IVD, and thus potentially present an alternative administration strategy. Further investigation will be needed to determine the long-term effects, elucidate the role of cellular homing versus paracrine signaling, and validate our observations on a large animal model.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Orthopaedic Surgery |
UniBE Contributor: |
Wangler, Sebastian |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2572-1143 |
Publisher: |
Wiley |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
31 Mar 2023 10:48 |
Last Modified: |
02 Apr 2023 02:15 |
Publisher DOI: |
10.1002/jsp2.1228 |
PubMed ID: |
36994461 |
Uncontrolled Keywords: |
cell therapy degeneration homing intervertebral disc mesenchymal stromal cells rat model |
BORIS DOI: |
10.48350/181237 |
URI: |
https://boris.unibe.ch/id/eprint/181237 |
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