PMID- 10341240
OWN - NLM
STAT- MEDLINE
DCOM- 19990616
LR  - 20220310
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 11
DP  - 1999 Jun 1
TI  - Transplants of fibroblasts genetically modified to express BDNF promote 
      regeneration of adult rat rubrospinal axons and recovery of forelimb function.
PG  - 4370-87
AB  - Adult mammalian CNS neurons do not normally regenerate their severed axons. This 
      failure has been attributed to scar tissue and inhibitory molecules at the injury 
      site that block the regenerating axons, a lack of trophic support for the 
      axotomized neurons, and intrinsic neuronal changes that follow axotomy, including 
      cell atrophy and death. We studied whether transplants of fibroblasts genetically 
      engineered to produce brain-derived neurotrophic factor (BDNF) would promote 
      rubrospinal tract (RST) regeneration in adult rats. Primary fibroblasts were 
      modified by retroviral-mediated transfer of a DNA construct encoding the human 
      BDNF gene, an internal ribosomal entry site, and a fusion gene of lacZ and 
      neomycin resistance genes. The modified fibroblasts produce biologically active 
      BDNF in vitro. These cells were grafted into a partial cervical hemisection 
      cavity that completely interrupted one RST. One and two months after lesion and 
      transplantation, RST regeneration was demonstrated with retrograde and 
      anterograde tracing techniques. Retrograde tracing with fluorogold showed that 
      approximately 7% of RST neurons regenerated axons at least three to four segments 
      caudal to the transplants. Anterograde tracing with biotinylated dextran amine 
      revealed that the RST axons regenerated through and around the transplants, grew 
      for long distances within white matter caudal to the transplant, and terminated 
      in spinal cord gray matter regions that are the normal targets of RST axons. 
      Transplants of unmodified primary fibroblasts or Gelfoam alone did not elicit 
      regeneration. Behavioral tests demonstrated that recipients of BDNF-producing 
      fibroblasts showed significant recovery of forelimb usage, which was abolished by 
      a second lesion that transected the regenerated axons.
FAU - Liu, Y
AU  - Liu Y
AD  - Department of Neurobiology and Anatomy, Medical College of Pennsylvania/Hahnemann 
      University, Philadelphia, Pennsylvania 19129, USA.
FAU - Kim, D
AU  - Kim D
FAU - Himes, B T
AU  - Himes BT
FAU - Chow, S Y
AU  - Chow SY
FAU - Schallert, T
AU  - Schallert T
FAU - Murray, M
AU  - Murray M
FAU - Tessler, A
AU  - Tessler A
FAU - Fischer, I
AU  - Fischer I
LA  - eng
GR  - NS24707/NS/NINDS NIH HHS/United States
GR  - F32 NS010090/NS/NINDS NIH HHS/United States
GR  - T32 HD007467/HD/NICHD NIH HHS/United States
GR  - HD07467/HD/NICHD NIH HHS/United States
GR  - NS10090/NS/NINDS NIH HHS/United States
GR  - P50 NS024707/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Axons/physiology
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cell Line
MH  - Female
MH  - Fibroblasts/physiology/transplantation
MH  - Forelimb/innervation
MH  - Gene Expression Regulation/*physiology
MH  - *Genetic Engineering
MH  - Graft Survival
MH  - Humans
MH  - *Nerve Regeneration
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Red Nucleus/*physiology/ultrastructure
MH  - Spinal Cord/*physiology/ultrastructure
PMC - PMC6782629
EDAT- 1999/05/26 00:00
MHDA- 1999/05/26 00:01
PMCR- 1999/12/01
CRDT- 1999/05/26 00:00
PHST- 1999/05/26 00:00 [pubmed]
PHST- 1999/05/26 00:01 [medline]
PHST- 1999/05/26 00:00 [entrez]
PHST- 1999/12/01 00:00 [pmc-release]
AID - 3086 [pii]
AID - 10.1523/JNEUROSCI.19-11-04370.1999 [doi]
PST - ppublish
SO  - J Neurosci. 1999 Jun 1;19(11):4370-87. doi: 10.1523/JNEUROSCI.19-11-04370.1999.