PMID- 21343916
OWN - NLM
STAT- MEDLINE
DCOM- 20111102
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 19
IP  - 5
DP  - 2011 May
TI  - "Same day" ex-vivo regional gene therapy: a novel strategy to enhance bone 
      repair.
PG  - 960-8
LID - 10.1038/mt.2011.2 [doi]
AB  - Ex-vivo regional gene therapy with bone marrow cells (BMCs) overexpressing bone 
      morphogenetic protein-2 (BMP-2) has demonstrated efficacy in healing critical 
      sized bone defects in preclinical studies. The purpose of this preclinical study 
      was to compare the osteoinductive potential of a novel "same day" ex-vivo 
      regional gene therapy versus a traditional two-step approach, which involves 
      culture expansion of the donor cells before implantation. In the "same day" 
      strategy buffy coat cells were harvested from the rat bone marrow, transduced 
      with a lentiviral vector-expressing BMP-2 for 1 hour and implanted into a rat 
      femoral defect in the same sitting. There was no significant difference (P = 
      0.22) with respect to the radiographic healing rates between the femoral defects 
      treated with the "same day" strategy (13/13; 100%) versus the traditional 
      two-step approach (11/14; 78%). However, the femoral defects treated with the 
      "same day" strategy induced earlier radiographic bone healing (P = 0.004) and 
      higher bone volume (BV) [micro-computed tomography (micro-CT); P < 0.001]. The 
      "same day" strategy represents a significant advance in the field of ex-vivo 
      regional gene therapy because it offers a solution to limitations associated with 
      the culture expansion process required in the traditional ex vivo approach. This 
      strategy should be cost-effective when adapted for human use.
FAU - Virk, Mandeep S
AU  - Virk MS
AD  - New England Musculoskeletal Institute, Department of Orthopedic Surgery, 
      University of Connecticut Health Center, Farmington, Connecticut 06030-5456, USA.
FAU - Sugiyama, Osamu
AU  - Sugiyama O
FAU - Park, Sang H
AU  - Park SH
FAU - Gambhir, Sanjiv S
AU  - Gambhir SS
FAU - Adams, Douglas J
AU  - Adams DJ
FAU - Drissi, Hicham
AU  - Drissi H
FAU - Lieberman, Jay R
AU  - Lieberman JR
LA  - eng
GR  - R01 AR057076/AR/NIAMS NIH HHS/United States
GR  - R01 AR057076-01A1/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110222
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Bone Morphogenetic Protein 2)
SB  - IM
MH  - Animals
MH  - Bone Development
MH  - Bone Marrow Cells/*cytology/metabolism
MH  - Bone Morphogenetic Protein 2/genetics/*metabolism
MH  - Bone Regeneration/*genetics
MH  - Bone Transplantation/methods
MH  - Cells, Cultured/virology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fracture Healing/*genetics
MH  - Fractures, Bone/metabolism/*therapy
MH  - Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/genetics/therapeutic use
MH  - Lentivirus/genetics
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Transduction, Genetic
PMC - PMC3098640
EDAT- 2011/02/24 06:00
MHDA- 2011/11/04 06:00
PMCR- 2012/05/01
CRDT- 2011/02/24 06:00
PHST- 2011/02/24 06:00 [entrez]
PHST- 2011/02/24 06:00 [pubmed]
PHST- 2011/11/04 06:00 [medline]
PHST- 2012/05/01 00:00 [pmc-release]
AID - S1525-0016(16)31896-2 [pii]
AID - 10.1038/mt.2011.2 [doi]
PST - ppublish
SO  - Mol Ther. 2011 May;19(5):960-8. doi: 10.1038/mt.2011.2. Epub 2011 Feb 22.