TY - JOUR
T1 - Human dental stem cells of the apical papilla associated to BDNF-loaded pharmacologically active microcarriers (PAMs) enhance locomotor function after spinal cord injury
AU - Kandalam, Saikrishna
AU - De Berdt, Pauline
AU - Ucakar, Bernard
AU - Vanvarenberg, Kevin
AU - Bouzin, Caroline
AU - Gratpain, Viridiane
AU - Diogenes, Anibal
AU - Montero-Menei, Claudia N.
AU - des Rieux, Anne
N1 - Funding Information:
The authors would like to thank Dr. John Bianco and Dr. Dario Carradori for their help with the BBB scoring as well as Laurence Sindji for her help with PAM formulation and characterization. Anne des Rieux is a Senior Research Associate at the FRS-FNRS (Fonds de la Recherche Scientifique, Belgique) and beneficiated from the support of the International Foundation for Research in Paraplegia (IRP, P155). The project was funded by the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), Erasmus Mundus programme, NanoFar doctorate and by ?R?gion Pays de La Loire?.
Funding Information:
The authors would like to thank Dr. John Bianco and Dr. Dario Carradori for their help with the BBB scoring as well as Laurence Sindji for her help with PAM formulation and characterization. Anne des Rieux is a Senior Research Associate at the FRS-FNRS (Fonds de la Recherche Scientifique, Belgique) and beneficiated from the support of the International Foundation for Research in Paraplegia (IRP, P155). The project was funded by the European Commission, Education, Audiovisual and Culture Executive Agency (EACEA), Erasmus Mundus programme, NanoFar doctorate and by “Région Pays de La Loire”.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/9/25
Y1 - 2020/9/25
N2 - 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.
AB - 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.
KW - Brain-derived neurotrophic factor (BDNF)
KW - Inflammation
KW - Neuroprotection
KW - Regenerative medicine
KW - Spinal cord injury
KW - Stem cells
UR - http://www.scopus.com/inward/record.url?scp=85089010315&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089010315&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2020.119685
DO - 10.1016/j.ijpharm.2020.119685
M3 - Article
C2 - 32712253
AN - SCOPUS:85089010315
VL - 587
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
M1 - 119685
ER -