PMID- 25581479
OWN - NLM
STAT- MEDLINE
DCOM- 20161006
LR  - 20220331
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Linking)
VI  - 24
IP  - 11
DP  - 2015
TI  - The role of brain-derived neurotrophic factor in bone marrow stromal 
      cell-mediated spinal cord repair.
PG  - 2209-20
LID - 10.3727/096368915X686201 [doi]
AB  - The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit 
      repair is thought to result from paracrine effects by secreted trophic factors 
      including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to 
      increase or silence BDNF production in BMSCs to investigate the role of BDNF in 
      BMSC-mediated neuroprotection. In a spinal cord organotypic culture, 
      BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% 
      compared with culture medium only. Only conditioned medium of BDNF-hypersecreting 
      BMSCs sustained this neuroprotective effect. In a rat model of spinal cord 
      contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a 
      subacute transplant of BDNF-hypersecreting BMSCs were significantly more spared 
      motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared 
      nervous tissue volume was improved by 68% with both control BMSCs and 
      BDNF-hypersecreting BMSCs. In addition, blood vessel density in the contusion 
      with BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and 
      sixfold higher compared with vehicle controls. BDNF-silenced BMSCs did not 
      survive the first week of transplantation, and no neuroprotective effect was 
      found at 4 weeks after transplantation. Together, our data broaden our 
      understanding of the role of BDNF in BMSC-mediated neuroprotection and 
      successfully exploit BDNF dependency to enhance anatomical spinal cord repair.
FAU - Ritfeld, Gaby J
AU  - Ritfeld GJ
AD  - Department of Physical Medicine and Rehabilitation, University of Pittsburgh 
      School of Medicine, Pittsburgh, PA, USA.
FAU - Patel, Ajay
AU  - Patel A
FAU - Chou, Alexander
AU  - Chou A
FAU - Novosat, Tabitha L
AU  - Novosat TL
FAU - Castillo, Deborah G
AU  - Castillo DG
FAU - Roos, Raymund A C
AU  - Roos RA
FAU - Oudega, Martin
AU  - Oudega M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150109
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/administration & dosage/*genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Genetic Therapy
MH  - Humans
MH  - Injections, Spinal
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Neovascularization, Physiologic
MH  - Neuroprotection
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/genetics/*therapy
MH  - *Spinal Cord Regeneration
EDAT- 2015/01/13 06:00
MHDA- 2016/10/08 06:00
CRDT- 2015/01/13 06:00
PHST- 2015/01/13 06:00 [entrez]
PHST- 2015/01/13 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
AID - content-CT-1291_Ritfeld_et_al [pii]
AID - 10.3727/096368915X686201 [doi]
PST - ppublish
SO  - Cell Transplant. 2015;24(11):2209-20. doi: 10.3727/096368915X686201. Epub 2015 
      Jan 9.