Article (Scientific journals)
Poly (D,L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord
Hurtado, Andres; Moon, Lawrence D F; Maquet, Véronique et al.
2006In Biomaterials, 27 (3), p. 430-442
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Keywords :
biomaterial; scaffold
Abstract :
[en] Freeze-dried poly(D,L-lactic acid) macroporous scaffold filled with a fibrin solution containing Schwann cells (SCs) lentivirally transduced to produce and secrete D15A, a bi-functional neurotrophin with brain-derived neurotrophic factor and neurotrophin-3 activity, and to express green fluorescent protein (GFP) were implanted in the completely transected adult rat thoracic spinal cord. Control rats were similarly injured and then implanted with scaffolds containing the fibrin solution with SCs lentivirally transduced to produce express GFP only or with the fibrin solution only. Transgene production and biological activity in vitro, SC survival within the scaffold in vitro and in vivo, scaffold integration, axonal regeneration and myelination, and hind limb motor function were analyzed at 1, 2, and 6 weeks after implantation. In vitro, lentivirally transduced SCs produced 87.5 ng/24 h/10(6) Cells of D15A as measured by neurotrophin-3 activity in ELISA. The secreted D15A was biologically active as evidenced by its promotion of neurite outgrowth of dorsal root ganglion neurons in culture. In vitro, SCs expressing GFP were present in the scaffolds for up to 6 It, the end of a typical surgery session. Implantation of SC-seeded scaffolds caused modest loss of spinal nervous tissue. Reactive astrocytes and chondroitin sulfate glycosaminoglycans were present in spinal tissue adjacent to the scaffold. Vascularization of the scaffold was ongoing at I week post-implantation. There were no apparent differences in scaffold integration and blood vessel formation between groups. A decreasing number of implanted (GFP-positive) SCs were found within the scaffold during the first 3 days after implantation. Apoptosis was identified as one of the mechanisms of cell death. At 1 week and later time points after implantation, few of the implanted SCs were present in the scaffold. Neurofilament-positive axons were found in the scaffold. At 6 weeks post-grafting, myelinated axons were observed within and at the external surface of the scaffold. Axons did not grow from the scaffold into the caudal cord. All groups demonstrated a similar improvement of hind limb motor function. Our findings demonstrated that few seeded SCs survived in vivo, which could account for the modest axonal regeneration response into and across the scaffold. For the development of SC-seeded macroporous scaffolds that effectively promote axonal regeneration in the injured spinal cord, the survival and/or total number of SCs in the scaffold needs to be improved. (c) 2005 Elsevier Ltd. All rights reserved.
Research center :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Chemistry
Materials science & engineering
Author, co-author :
Hurtado, Andres;  University of Miami, School of Medicine, USA > The Miami Project to Cure Paralysis
Moon, Lawrence D F;  University of Miami, School of Medicine, USA > The Miami Project to Cure Paralysis
Maquet, Véronique;  Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Blits, Bas;  University of Miami, School of Medicine, USA > The Miami Project to Cure Paralysis
Jérôme, Robert ;  Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Oudega, Martin;  University of Miami School of Medicine, USA > Department of Neurological Surgery
Language :
English
Title :
Poly (D,L-lactic acid) macroporous guidance scaffolds seeded with Schwann cells genetically modified to secrete bi-functional neurotrophin implanted in the completely transected adult rat thoracic spinal cord
Publication date :
January 2006
Journal title :
Biomaterials
ISSN :
0142-9612
eISSN :
1878-5905
Publisher :
Elsevier, Oxford, United Kingdom
Volume :
27
Issue :
3
Pages :
430-442
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique
The Daniel Heumann Foundation, Florida State, and The Miami Project
Commentary :
The authors acknowledge Biomaterials (Elsevier) for allowing them to archive this paper.
Available on ORBi :
since 02 February 2009

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