Transplantation of encapsulated autologous olfactory ensheathing cell populations expressing chondroitinase for spinal cord injury: A safety and feasibility study in companion dogs.
canine translational model
cell therapy / transplantation
chondroitinase ABC
hydrogel encapsulation
neurology
neuroscience
olfactory ensheathing cells
spinal cord injury
spontaneous animal model
Journal
Journal of tissue engineering and regenerative medicine
ISSN: 1932-7005
Titre abrégé: J Tissue Eng Regen Med
Pays: England
ID NLM: 101308490
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
08
05
2022
received:
21
02
2022
accepted:
24
05
2022
pubmed:
11
6
2022
medline:
9
9
2022
entrez:
10
6
2022
Statut:
ppublish
Résumé
Spinal cord injury (SCI) can cause irreversible paralysis, with no regenerative treatment clinically available. Dogs with natural SCI present an established model and can facilitate translation of experimental findings in rodents to people. We conducted a prospective, single arm clinical safety study in companion dogs with chronic SCI to characterize the feasibility of intraspinal transplantation of hydrogel-encapsulated autologous mucosal olfactory ensheathing cell (mOEC) populations expressing chondroitinase ABC (chABC). mOECs and chABC are both promising therapies for SCI, and mOECs expressing chABC drive greater voluntary motor recovery than mOECs alone after SCI in rats. Canine mOECs encapsulated in collagen hydrogel can be matched in stiffness to canine SCI. Four dogs with complete and chronic loss of function caudal to a thoraco-lumbar lesion were recruited. After baseline measures, olfactory mucosal biopsy was performed and autologous mOECs cultured and transduced to express chABC, then hydrogel-encapsulated and percutaneously injected into the spinal cord. Dogs were monitored for 6 months with repeat clinical examinations, spinal MRI, kinematic gait and von Frey assessment. No adverse effects or significant changes on neurological examination were detected. MRI revealed large and variable lesions, with no spinal cord compression or ischemia visible after hydrogel transplantation. Owners reported increased pelvic-limb reflexes with one dog able to take 2-3 unsupported steps, but gait-scoring and kinematic analysis showed no significant improvements. This novel combination approach to regeneration after SCI is therefore feasible and safe in paraplegic dogs in a clinical setting. A randomised-controlled trial in this translational model is proposed to test efficacy.
Identifiants
pubmed: 35686704
doi: 10.1002/term.3328
pmc: PMC9542194
doi:
Substances chimiques
Hydrogels
0
Chondroitinases and Chondroitin Lyases
EC 4.2.2.-
Chondroitin ABC Lyase
EC 4.2.2.20
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
788-798Informations de copyright
© 2022 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.
Références
Exp Neurol. 2008 Feb;209(2):483-96
pubmed: 17936753
J Vet Intern Med. 2016 Jan-Feb;30(1):206-14
pubmed: 26520829
PLoS Biol. 2016 May 31;14(5):e1002468
pubmed: 27244556
Sci Rep. 2018 Jan 10;8(1):325
pubmed: 29321494
Spinal Cord. 2007 Mar;45(3):190-205
pubmed: 17179973
Stem Cells Transl Med. 2015 Oct;4(10):1173-86
pubmed: 26273065
Vet J. 2013 Aug;197(2):216-9
pubmed: 23246235
BMC Neurosci. 2007 Sep 18;8:77
pubmed: 17877823
Prev Vet Med. 2009 May 1;89(1-2):121-7
pubmed: 19303151
Eur Spine J. 2015 May;24(5):919-30
pubmed: 25001890
J Funct Biomater. 2012 Nov 15;3(4):839-63
pubmed: 24955749
Acta Orthop Scand. 1951;20(4):280-93
pubmed: 14894198
Brain. 2018 Apr 1;141(4):1017-1027
pubmed: 29444239
World Neurosurg. 2015 Feb;83(2):251-6
pubmed: 23891878
J Neurol Sci. 2016 Aug 15;367:311-8
pubmed: 27423610
Spinal Cord. 2018 Feb;56(2):133-141
pubmed: 29057987
J Tissue Eng. 2020 Jul 2;11:2041731420934806
pubmed: 32670538
J Neurotrauma. 2010 Jan;27(1):1-19
pubmed: 19698073
J Neurotrauma. 2017 Nov 1;34(21):2994-3002
pubmed: 28462632
Exp Neurol. 2021 Jun;340:113660
pubmed: 33647272
Nat Rev Neurosci. 2020 Mar;21(3):139-152
pubmed: 32042145
J Comp Pathol. 1978 Apr;88(2):303-15
pubmed: 659683
J Vet Intern Med. 2013 Nov-Dec;27(6):1318-33
pubmed: 24010573
Biomaterials. 2015 Feb;41:89-96
pubmed: 25522968
J Am Vet Med Assoc. 2003 Mar 15;222(6):762-9
pubmed: 12675299
Brain Pathol. 2006 Apr;16(2):99-109
pubmed: 16768749
Neuropsychopharmacology. 2014 Jan;39(1):169-88
pubmed: 24002187
PLoS One. 2019 Mar 6;14(3):e0213252
pubmed: 30840687
Adv Healthc Mater. 2017 May;6(10):
pubmed: 28247563
Brain. 2012 Nov;135(Pt 11):3227-37
pubmed: 23169917
J Neurotrauma. 2004 Apr;21(4):429-40
pubmed: 15115592
J Neuropathol Exp Neurol. 2011 Aug;70(8):703-14
pubmed: 21760535
Cell Transplant. 2008;16(10):1021-7
pubmed: 18351018
Adv Healthc Mater. 2018 Jun;7(11):e1701139
pubmed: 29658175
J Tissue Eng Regen Med. 2022 Sep;16(9):788-798
pubmed: 35686704
Exp Neurol. 2019 Nov;321:113032
pubmed: 31398353
Exp Neurol. 2011 May;229(1):2-9
pubmed: 20816825
J Neurotrauma. 2017 Jun 15;34(12):2007-2018
pubmed: 28230415
Brain Res. 2009 Dec 15;1303:26-31
pubmed: 19782053
Sci China Life Sci. 2016 Jul;59(7):647-55
pubmed: 27333785
J Control Release. 2020 May 10;321:553-563
pubmed: 32087299
Nat Neurosci. 2019 Aug;22(8):1269-1275
pubmed: 31235933