Preferential Enhancement of Sensory and Motor Axon Regeneration by Combining Extracellular Matrix Components with Neurotrophic Factors

被引:8
作者
Santos, Daniel [1 ,2 ,3 ]
Gonzalez-Perez, Francisco [1 ,2 ,3 ]
Giudetti, Guido [4 ]
Micera, Silvestro [4 ,5 ]
Udina, Esther [1 ,2 ,3 ]
Del Valle, Jaume [1 ,2 ,3 ]
Navarro, Xavier [1 ,2 ,3 ]
机构
[1] Univ Autonoma Barcelona, Inst Neurosci, E-08193 Bellaterra, Spain
[2] Univ Autonoma Barcelona, Dept Cell Biol Physiol & Immunol, E-08193 Bellaterra, Spain
[3] Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08193 Bellaterra, Spain
[4] Scuola Super Sant Anna, BioRobot Inst, Viale Rinaldo Piaggio 34, I-56025 Pontedera, Italy
[5] Ecole Polytech Fed Lausanne, Sch Engn, Bertarelli Fdn Chair Translat NeuroEngn,Inst Bioe, Translat Neural Engn,Lab Ctr Neuroprosthet & Inte, CH-1015 Lausanne, Switzerland
来源
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2017年 / 18卷 / 01期
关键词
neurotrophic factors; BDNF; NGF; NT3; extracellular matrix; motor axons; sensory axons; nerve regeneration; reinnervation; NERVE GROWTH-FACTOR; NEURONS IN-VITRO; PERIPHERAL-NERVE; NEURITE OUTGROWTH; SCHWANN-CELLS; FUNCTIONAL RECOVERY; TUBE REPAIR; INJURY; RAT; RELEASE;
D O I
10.3390/ijms18010065
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively. For in vivo studies, the rat sciatic nerve was transected and repaired with a silicone tube filled with a collagen and laminin matrix with NGF/NT3 encapsulated in poly(lactic-co-glycolic acid) (PLGA) microspheres (MP) (LM + MP. NGF/NT3), or a collagen and fibronectin matrix with BDNF in PLGA MPs (FN + MP. BDNF). Retrograde labeling and functional tests showed that LM + MP. NGF/NT3 increased the number of regenerated sensory neurons and improved sensory functional recovery, whereas FN + MP. BDNF preferentially increased regenerated motoneurons and enhanced motor functional recovery. Therefore, combination of ECM molecules with NTFs may be a good approach to selectively enhance motor and sensory axons regeneration and promote appropriate target reinnervation.
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页数:16
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