Transplanted neural progenitor cells expressing mutant NT3 promote myelination and partial hindlimb recovery in the chronic phase after spinal cord injury.
Neutrotrophin-3 (NT3) plays a protective role in injured central nervous system tissues through interaction with trk receptors. To enhance the regeneration of damaged tissue, a combination therapy with cell transplantation and neurotrophins has been under development. We examined whether the transplantation of neural progenitor cells (NPCs) secreting NT3/D15A, a multi-neurotrophin with the capacity to bind both trkB and trkC, would enhance the repair of damaged tissues and the functional recovery in a chronic phase of spinal cord injury. The cultured NPCs with lentiviral vector containing either GFP or NT3/D15A were transplanted into the contused spinal cord at 6 weeks after the initial thoracic injury. Eight weeks after the transplantation, the NT3/D15A transplants displayed better survival than the GFP transplants, and they exhibited enhanced myelin formation and partial improvement of hindlimb function. Our study revealed that NT3/D15A produced positive effects in injured spinal cords even in the chronic phase. These effects suggest an enhanced neurotrophin-trk signaling by NT3/D15A.
Kusano
Kazuo
K
Department of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo, Tokyo 113-8519, Japan. kusano.orth@tmd.ac.jp
Enomoto
Mitsuhiro
M
Hirai
Takashi
T
Tsoulfas
Pantelis
P
Sotome
Shinichi
S
Shinomiya
Kenichi
K
Okawa
Atsushi
A
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D006085:Graft Survival; D006614:Hindlimb / Q000502:physiology; D006801:Humans; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration; D009474:Neurons / Q000378:metabolism* / Q000637:transplantation*; D020933:Neurotrophin 3 / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000503:physiopathology / Q000601:surgery*; D013194:Staining and Labeling; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D014162:Transfection
D020933:Neurotrophin 3