PMID- 19752394
OWN - NLM
STAT- MEDLINE
DCOM- 20091222
LR  - 20210206
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 114
IP  - 20
DP  - 2009 Nov 12
TI  - The therapeutic effect of bone marrow-derived liver cells in the phenotypic 
      correction of murine hemophilia A.
PG  - 4552-61
LID - 10.1182/blood-2009-02-202788 [doi]
AB  - The transdifferentiation of bone marrow cells (BMCs) into hepatocytes has created 
      enormous interest in applying this process to the development of cellular 
      medicine for degenerative and genetic diseases. Because the liver is the primary 
      site of factor VIII (FVIII) synthesis, we hypothesized that the partial 
      replacement of mutated liver cells by healthy cells in hemophilia A mice could 
      manage the severity of the bleeding disorder. We perturbed the host liver with 
      acetaminophen to facilitate the engraftment and hepatic differentiation of 
      lineage-depleted enhanced green fluorescent protein-expressing BMCs. 
      Immunohistochemistry experiments with the liver tissue showed that the 
      donor-derived cells expressed the markers of both hepatocytes (albumin and 
      cytokeratin-18) and endothelial cells (von Willebrand factor). The results of 
      fluorescent in situ hybridization and immunocytochemistry experiments suggested 
      that differentiation was direct in this model. The BMC-recipient mice expressed 
      FVIII protein and survived in a tail clip challenge experiment. Furthermore, a 
      coagulation assay confirmed that the plasma FVIII activity was maintained at 
      20.4% (+/- 3.6%) of normal pooled plasma activity for more than a year without 
      forming its inhibitor. Overall, this report demonstrated that BMCs rescued the 
      bleeding phenotype in hemophilia A mice, suggesting a potential therapy for this 
      and other related disorders.
FAU - Yadav, Neelam
AU  - Yadav N
AD  - Stem Cell Biology Laboratory, National Institute of Immunology, Aruna Asaf Ali 
      Marg, New Delhi, India.
FAU - Kanjirakkuzhiyil, Sumod
AU  - Kanjirakkuzhiyil S
FAU - Kumar, Suresh
AU  - Kumar S
FAU - Jain, Manish
AU  - Jain M
FAU - Halder, Ashutosh
AU  - Halder A
FAU - Saxena, Renu
AU  - Saxena R
FAU - Mukhopadhyay, Asok
AU  - Mukhopadhyay A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090914
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*cytology/metabolism
MH  - Bone Marrow Transplantation
MH  - Cell Transdifferentiation
MH  - Factor VIII/biosynthesis
MH  - Female
MH  - Flow Cytometry
MH  - Hemophilia A/*therapy
MH  - Hepatocytes/*cytology/metabolism
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mice
MH  - Phenotype
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2009/09/16 06:00
MHDA- 2009/12/23 06:00
CRDT- 2009/09/16 06:00
PHST- 2009/09/16 06:00 [entrez]
PHST- 2009/09/16 06:00 [pubmed]
PHST- 2009/12/23 06:00 [medline]
AID - S0006-4971(20)38939-4 [pii]
AID - 10.1182/blood-2009-02-202788 [doi]
PST - ppublish
SO  - Blood. 2009 Nov 12;114(20):4552-61. doi: 10.1182/blood-2009-02-202788. Epub 2009 
      Sep 14.