Dental Apical Papilla as Therapy for Spinal Cord Injury.
Stem cells of the apical papilla (SCAP) represent great promise regarding treatment of neural tissue damage, such as spinal cord injury (SCI). They derive from the neural crest, express numerous neurogenic markers, and mediate neurite outgrowth and axonal targeting. The goal of the present work was to investigate for the first time their potential to promote motor recovery after SCI in a rat hemisection model when delivered in their original stem cell niche-that is, by transplantation of the human apical papilla tissue itself into the lesion. Control groups consisted of animals subjected to laminectomy only (shams) and to lesion either untreated or injected with a fibrin hydrogel with or without human SCAP. Basso-Beattie-Bresnahan locomotor scores at 1 and 3 d postsurgery confirmed early functional decline in all SCI groups. This significant impairment was reversed, as seen in CatWalk analyses, after transplantation of apical papilla into the injured spinal cord wound, whereas the other groups demonstrated persistent functional impairment. Moreover, tactile allodynia did not develop as an unwanted side effect in any of the groups, even though the SCAP hydrogel group showed higher expression of the microglial marker Iba-1, which has been frequently associated with allodynia. Notably, the apical papilla transplant group presented with reduced Iba-1 expression level. Masson trichrome and human mitochondria staining showed the preservation of the apical papilla integrity and the presence of numerous human cells, while human cells could no longer be detected in the SCAP hydrogel group at the 6-wk postsurgery time point. Altogether, our data suggest that the transplantation of a human apical papilla at the lesion site improves gait in spinally injured rats and reduces glial reactivity. It also underlines the potential interest for the application of delivering SCAP in their original niche, as compared with use of a fibrin hydrogel.
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
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De Berdt
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
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J
Vanacker
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
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Ucakar
Université Catholique de Louvain, Louvain Drug Research Institute, Translational Research from Experimental and Clinical Pharmacology to Treatment Optimization, Brussels, Belgium.
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Elens
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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Diogenes
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium.
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JG
Leprince
Université Catholique de Louvain, Institute of Neuroscience, Brussels, Belgium.
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Deumens
Université Catholique de Louvain, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Brussels, Belgium Université Catholique de Louvain, Institute of Condensed Matter and Nanosciences, Bio- and Soft Matter Unit, Louvain-la-Neuve, Belgium anne.desrieux@uclouvain.be.
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des Rieux
D000293:Adolescent; D000818:Animals; D059350:Chronic Pain / Q000628:therapy; D003771:Dental Papilla / Q000166:cytology / Q000637:transplantation*; D006801:Humans; D008124:Locomotion; D051381:Rats; D013116:Spinal Cord / Q000502:physiology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D033581:Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
central nervous system; dental stem cells; fibrin hydrogel; pain; regenerative medicine; spinal cord hemisection