PMID- 19384160
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20090422
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 87
IP  - 8
DP  - 2009 Apr 27
TI  - Potential feasibility of early bone marrow cell injection into the spleen for 
      creating functional hepatocytes.
PG  - 1147-54
LID - 10.1097/TP.0b013e31819e0528 [doi]
AB  - BACKGROUND: Bone marrow cells (BMCs) are believed to have the ability to generate 
      functional hepatocytes and have some merits as a therapeutic modality for 
      metabolic liver diseases. However, the appearance of BMC-derived hepatocytes 
      (BMDHs) is low. We hypothesized that early BMC injection would be feasible for 
      creating BMDHs for two main reasons: (1) the liver is a hematopoietic organ in 
      neonatal rats and (2) it may allow sufficient time to generate more BMDHs before 
      severe liver injury occurs. METHODS: We used Long Evans Cinnamon (LEC) rats as 
      recipients, a model of (1) Wilson disease and (2) liver carcinogenesis. Green 
      fluorescent protein-expressing BMCs were injected into newborn LEC rats through 
      the spleen. The oxidative activity of ceruloplasmin, which is low in LEC rats, 
      was measured to evaluate the treatment. In addition, we performed fluorescence in 
      situ hybridization to clarify the origin of the BMDHs and immunohistochemical 
      analysis to confirm whether these BMDHs had malignant potential. RESULTS: At 18 
      months after injection, we found some green fluorescent protein-expressing areas 
      macroscopically in the liver of treated LEC rats. The oxidative activity of 
      ceruloplasmin increased in treated LEC rats (n=7) and were much higher than that 
      in untreated LEC rats (P=0.015). Moreover, we confirmed that the BMDHs were 
      generated by cell fusion and was not detected in any of the neoplastic lesions or 
      cholngiofibrotic regions. CONCLUSION: Our results suggest that this novel 
      strategy for creating BMDHs is effective and safe.
FAU - Misawa, Ryosuke
AU  - Misawa R
AD  - First Department of Surgery, Shinshu University School of Medicine, Matsumoto, 
      Nagano, Japan.
FAU - Soeda, Junpei
AU  - Soeda J
FAU - Ise, Hirohiko
AU  - Ise H
FAU - Takahashi, Masafumi
AU  - Takahashi M
FAU - Kubota, Koji
AU  - Kubota K
FAU - Mita, Atsuyoshi
AU  - Mita A
FAU - Nakata, Takenari
AU  - Nakata T
FAU - Miyagawa, Shinichi
AU  - Miyagawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 1.16.3.1 (Ceruloplasmin)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Bone Marrow Transplantation/*methods
MH  - Cell Differentiation/*physiology
MH  - Ceruloplasmin/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/genetics
MH  - Hepatocytes/cytology/*physiology
MH  - Hepatolenticular Degeneration/*surgery
MH  - Liver Neoplasms/surgery
MH  - Pregnancy
MH  - Rats
MH  - Rats, Long-Evans
MH  - Regeneration/physiology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spleen/*surgery
EDAT- 2009/04/23 09:00
MHDA- 2009/05/15 09:00
CRDT- 2009/04/23 09:00
PHST- 2009/04/23 09:00 [entrez]
PHST- 2009/04/23 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
AID - 00007890-200904270-00008 [pii]
AID - 10.1097/TP.0b013e31819e0528 [doi]
PST - ppublish
SO  - Transplantation. 2009 Apr 27;87(8):1147-54. doi: 10.1097/TP.0b013e31819e0528.