PMID- 18791205
OWN - NLM
STAT- MEDLINE
DCOM- 20090410
LR  - 20081216
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 81
IP  - 1
DP  - 2009 Jan 1
TI  - Bone marrow CXCR4 induction by cultivation enhances therapeutic angiogenesis.
PG  - 169-77
LID - 10.1093/cvr/cvn247 [doi]
AB  - AIMS: The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor 
      (CXCR4, CXC chemokine receptor 4) play a critical role in the process of 
      post-natal neovascularization. Here, we investigated the role of CXCR4(+) bone 
      marrow cells (BMCs) in neovascularization in a murine hindlimb ischaemia model. 
      METHODS AND RESULTS: We found that the expression of CXCR4 in BMCs was 
      specifically upregulated by cultivation; therefore, we used freshly isolated BMCs 
      and cultivated BMCs, designated as BMC(Fr) and BMC(Cul), respectively. The 
      increased CXCR4 expression corresponded to the migratory capacity in response to 
      SDF-1 alpha. Real-time reverse transcription-polymerase chain reaction and 
      immunohistochemical analyses revealed that SDF-1 alpha expression was 
      significantly increased in the ischaemic limbs of mice. Blood flow perfusion and 
      capillary density were significantly accelerated in mice implanted with BMC(Cul) 
      as compared with those in mice implanted with BMC(Fr). The stimulatory effect of 
      BMC(Cul) on neovascularization was significantly impaired when BMC(Cul) derived 
      from CXCR4(+/-) mice were implanted. The implanted BMC(Cul) showed high retention 
      in the ischaemic limbs. Further, the implantation of BMC(Cul) significantly 
      increased the expression of interleukin (IL)-1 beta and vascular endothelial 
      growth factor-A in the ischaemic limbs. CONCLUSION: The upregulation of CXCR4 
      expression by cultivation may serve as a useful source of BMCs for accelerating 
      therapeutic angiogenesis in ischaemic cardiovascular diseases.
FAU - Shiba, Yuji
AU  - Shiba Y
AD  - Department of Cardiovascular Medicine, Shinshu University Graduate School of 
      Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
FAU - Takahashi, Masafumi
AU  - Takahashi M
FAU - Hata, Takeki
AU  - Hata T
FAU - Murayama, Hideki
AU  - Murayama H
FAU - Morimoto, Hajime
AU  - Morimoto H
FAU - Ise, Hirohiko
AU  - Ise H
FAU - Nagasawa, Takashi
AU  - Nagasawa T
FAU - Ikeda, Uichi
AU  - Ikeda U
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080912
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CXCL12/metabolism
MH  - Disease Models, Animal
MH  - Hindlimb/blood supply/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Ischemia/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Nude
MH  - Mice, Transgenic
MH  - Neovascularization, Physiologic/genetics/*physiology
MH  - RNA, Messenger/metabolism
MH  - Receptors, CXCR4/*genetics/*metabolism
MH  - Regional Blood Flow/physiology
MH  - Up-Regulation/*physiology
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2008/09/16 09:00
MHDA- 2009/04/11 09:00
CRDT- 2008/09/16 09:00
PHST- 2008/09/16 09:00 [entrez]
PHST- 2008/09/16 09:00 [pubmed]
PHST- 2009/04/11 09:00 [medline]
AID - cvn247 [pii]
AID - 10.1093/cvr/cvn247 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2009 Jan 1;81(1):169-77. doi: 10.1093/cvr/cvn247. Epub 2008 Sep 
      12.