PMID- 20647998
OWN - NLM
STAT- MEDLINE
DCOM- 20110119
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 18
IP  - 10
DP  - 2010 Oct
TI  - Optimization of targeted cell replacement therapy: a new approach for lung 
      disease.
PG  - 1830-6
LID - 10.1038/mt.2010.142 [doi]
AB  - Cell replacement therapy is a promising approach for treatment of lung disease 
      such as cystic fibrosis, although rates of engraftment need to be improved. We 
      previously showed improved cell retention in the lung using transtracheal 
      delivery compared to intravenous injection. Here, we optimized other parameters 
      of cell delivery using 7-day cultured bone marrow cells (BMCs). Retention of BMC 
      in the lung was dose-dependent. Naphthalene treatment had maximal effects on BMC 
      retention when given 2 days before cell delivery. Naphthalene treatment of the 
      donor amplified a CCSP(+) population and increased retention efficiency in the 
      recipient. Repeated naphthalene treatment and repeated cell delivery both 
      resulted in greater retention. The contribution of the second cell dose was 
      minimal suggesting that a second delivery of BMC promotes proliferation of the 
      first. Busulfan-induced myelosuppression augmented retention of exogenous BMC by 
      up to 20-fold. These BMC helped CCSP reconstitution. Using the optimal delivery 
      techniques and cytokeratin-18-driven green fluorescent protein (GFP) reporter 
      mice, we detected threefold more GFP suggesting more BMC differentiated to 
      epithelial cells. We propose that improved engraftment in the lung will increase 
      cell replacement and thus be a more efficient therapeutic approach for various 
      lung diseases.
FAU - Duchesneau, Pascal
AU  - Duchesneau P
AD  - Division of Thoracic Surgery, Latner Thoracic Surgery Research Laboratories, 
      Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
FAU - Wong, Amy P
AU  - Wong AP
FAU - Waddell, Thomas K
AU  - Waddell TK
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100720
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Naphthalenes)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 2166IN72UN (naphthalene)
SB  - IM
MH  - Animals
MH  - Cell Movement/physiology
MH  - Cell- and Tissue-Based Therapy/*methods
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Lung Diseases/chemically induced/metabolism/*therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Naphthalenes/toxicity
MH  - Polymerase Chain Reaction
PMC - PMC2951559
EDAT- 2010/07/22 06:00
MHDA- 2011/01/20 06:00
PMCR- 2011/10/01
CRDT- 2010/07/22 06:00
PHST- 2010/07/22 06:00 [entrez]
PHST- 2010/07/22 06:00 [pubmed]
PHST- 2011/01/20 06:00 [medline]
PHST- 2011/10/01 00:00 [pmc-release]
AID - S1525-0016(16)30867-X [pii]
AID - 10.1038/mt.2010.142 [doi]
PST - ppublish
SO  - Mol Ther. 2010 Oct;18(10):1830-6. doi: 10.1038/mt.2010.142. Epub 2010 Jul 20.