Target muscles for retrograde gene delivery to specific spinal cord segments.
Targeted retrograde gene delivery into the injured spinal cord is less invasive for the damaged tissue. One of the advantages of this approach is the possible selection of target organs according to the level of spinal cord injury. We evaluated nine candidate target organs for retrograde delivery of an adenovirus vector carrying beta-galactosidase (AdV-LacZ) gene to cervical, thoracic and lumbar spinal cord segments. One week after vector injection into each muscle, we assessed the LacZ gene expression in the spinal cord by X-gal staining. The most appropriate target organs with high transduction efficacy were the sternomastoid and clavotrapezius muscles for cervical spinal cord, tibialis anterior and the gastrocnemius muscles for the lumbar spinal cord. Retrograde gene delivery to the thoracic spinal cord was inefficient probably due to the small number of anterior horn neurons in the region. Gene expression was mainly identified over the anatomical area of innervation and not into other body organs. Our results suggested that retrograde delivery of adenovirus genome to the cervical and lumbar spinal cord segments seems feasible by injection of an adenoviral vector into the appropriate target organ. Adenovirus vector is an efficient retrograde tracer since it can deliver the carried gene to a wide area of the spinal cord and not to other body organs.
Nakajima
Hideaki
H
Division of Orthopaedics and Rehabilitation Medicine, Department of Surgery, Faculty of Medical Sciences, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193, Fukui, Japan. nhideaki@u-fukui.ac.jp
Uchida
Kenzo
K
Kobayashi
Shigeru
S
Inukai
Tomoo
T
Yayama
Takafumi
T
Sato
Ryuichiro
R
Mwaka
Erisa
E
Baba
Hisatoshi
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007763:Lac Operon / Q000235:genetics; D008297:Male; D009046:Motor Neurons / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism; D009334:Neck Muscles / Q000294:innervation / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000235:genetics / Q000378:metabolism / Q000628:therapy