Human dental stem cells of the apical papilla associated to BDNF-loaded pharmacologically active microcarriers (PAMs) enhance locomotor function after spinal cord injury
| Autor: | Pauline De Berdt, Claudia N. Montero-Menei, Kevin Vanvarenberg, Anne des Rieux, Caroline Bouzin, Anibal R. Diogenes, Bernard Ucakar, Viridiane Gratpain, Saikrishna Kandalam |
|---|---|
| Přispěvatelé: | Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Recherche Expérimentale et Clinique (IREC), The University of Texas at San Antonio (UTSA) |
| Rok vydání: | 2020 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Pharmaceutical Science Inflammation 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Neuroprotection Lesion 03 medical and health sciences 0302 clinical medicine stomatognathic system Neurotrophic factors medicine Animals Humans Spinal cord injury Spinal Cord Injuries Neurons biology business.industry Brain-Derived Neurotrophic Factor Mesenchymal stem cell Mesenchymal Stem Cells 021001 nanoscience & nanotechnology medicine.disease Rats 3. Good health Nitric oxide synthase Neuroprotective Agents Spinal Cord nervous system biology.protein Stem cell medicine.symptom 0210 nano-technology business |
| Zdroj: | International Journal of Pharmaceutics International Journal of Pharmaceutics, Elsevier, 2020, 587, pp.119685-. ⟨10.1016/j.ijpharm.2020.119685⟩ |
| ISSN: | 0378-5173 |
| Popis: | There is no treatment for spinal cord injury (SCI) that fully repairs the damages. One strategy is to inject mesenchymal stem cells around the lesion to benefit from their immunomodulatory properties and neuroprotective effect. Our hypothesis was that the combination of dental stem cells from the apical papilla (SCAP) with pharmacologically active microcarriers (PAMs) releasing brain-derived neurotrophic factor (BDNF) would improve rat locomotor function by immunomodulation and neuroprotection. BDNF-PAMs were prepared by solid/oil/water emulsion of poly(L-lactide-co-glycolide) and nanoprecipitated BDNF and subsequent coating with fibronectin. SCAP were then seeded on BDNF-PAMs. SCAP expression of neuronal and immunomodulatory factors was evaluated in vitro. SCAP BDNF-PAMs were injected in a rat spinal cord contusion model and their locomotor function was evaluated by Basso, Beattie, and Bresnahan (BBB) scoring. Impact on inflammation and neuroprotection/axonal growth was evaluated by immunofluorescence. Culture on PAMs induced the overexpression of immunomodulatory molecules and neural/neuronal markers. Injection of SCAP BDNF-PAMs at the lesion site improved rat BBB scoring, reduced the expression of inducible nitric oxide synthase and increased the expression of βIII tubulin, GAP43, and 5-HT. These results confirm the suitability and versatility of PAMs as combined drug and cell delivery system for regenerative medicine applications but also that BDNF-PAMs potentialize the very promising therapeutic potential of SCAP in the scope of SCI. |
| Databáze: | OpenAIRE |
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