PMID- 11421585
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20171116
IS  - 0014-4886 (Print)
IS  - 0014-4886 (Linking)
VI  - 170
IP  - 1
DP  - 2001 Jul
TI  - The regrowth of axons within tissue defects in the CNS is promoted by implanted 
      hydrogel matrices that contain BDNF and CNTF producing fibroblasts.
PG  - 72-84
AB  - In this study we demonstrate the potential for combining biocompatible polymers 
      with genetically engineered cells to elicit axon regrowth across tissue defects 
      in the injured CNS. Eighteen- to 21-day-old rats received implants of poly 
      N-(2-hydroxypropyl)-methacrylamide (HPMA) hydrogels containing RGD peptide 
      sequences that had been infiltrated with control (untransfected) fibroblasts (n = 
      8), fibroblasts engineered to express brain-derived neurotrophic factor (BDNF) (n 
      = 5), ciliary neurotrophic factor (CNTF) (n = 5), or a mixture of BDNF and CNTF 
      expressing fibroblasts (n = 11). Fibroblasts were prelabeled with Hoechst 33342. 
      Cell/polymer constructs were inserted into cavities made in the left optic tract, 
      between thalamus and superior colliculus. After 4-8 weeks, retinal projections 
      were analyzed by injecting right eyes with cholera toxin (B-subunit). Rats were 
      perfused 24 h later and sections were immunoreacted to visualize retinal axons, 
      other axons (RT97 antibody), host astrocytes and macrophages, donor fibroblasts, 
      and extracellular matrix molecules. The volume fraction (VF) of each gel that was 
      occupied by RT97(+) axons was quantified. RT-PCR confirmed expression of the 
      transgenes prior to, and 5 weeks after, transplantation. Compared to control rats 
      (mean VF = 0.02 +/- 0.01% SEM) there was increased ingrowth of RT97(+) axons into 
      implants in CNTF (mean VF = 0.33 +/- 0.19%) and BDNF (mean VF = 0.62 +/-0.19%) 
      groups. Axon growth into hydrogels in the mixed BDNF/CNTF group (mean VF = 3.58 
      +/- 0.92%) was significantly greater (P < 0.05) than in the BDNF or CNTF 
      fibroblast groups. Retinal axons exhibited a complex branching pattern within 
      gels containing BDNF or BDNF/CNTF fibroblasts; however, they regrew the greatest 
      distances within implants containing both BDNF and CNTF expressing cells.
CI  - Copyright 2001 Academic Press.
FAU - Loh, N K
AU  - Loh NK
AD  - Department of Anatomy and Human Biology, The University of Western Australia, 
      Crawley, Perth, WA 6009, Australia.
FAU - Woerly, S
AU  - Woerly S
FAU - Bunt, S M
AU  - Bunt SM
FAU - Wilton, S D
AU  - Wilton SD
FAU - Harvey, A R
AU  - Harvey AR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antigens, Differentiation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Drug Implants)
RN  - 0 (Fibronectins)
RN  - 25852-47-5 (Hydrogel, Polyethylene Glycol Dimethacrylate)
SB  - IM
MH  - Animals
MH  - Antigens, Differentiation/metabolism
MH  - Axons/drug effects/*metabolism
MH  - Brain Injuries/pathology/*therapy
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/pharmacology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Ciliary Neurotrophic Factor/*biosynthesis/genetics/pharmacology
MH  - Disease Models, Animal
MH  - Drug Implants
MH  - Extracellular Matrix/metabolism
MH  - Female
MH  - Fibroblasts/cytology/*metabolism/transplantation
MH  - Fibronectins/metabolism
MH  - Hydrogel, Polyethylene Glycol Dimethacrylate/metabolism/pharmacology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Retina/cytology
MH  - Superior Colliculi/cytology
MH  - Thalamus/cytology
MH  - Transgenes
MH  - Visual Pathways/drug effects/pathology
EDAT- 2001/06/26 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/06/26 10:00
PHST- 2001/06/26 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/06/26 10:00 [entrez]
AID - S0014-4886(01)97692-7 [pii]
AID - 10.1006/exnr.2001.7692 [doi]
PST - ppublish
SO  - Exp Neurol. 2001 Jul;170(1):72-84. doi: 10.1006/exnr.2001.7692.