PMID- 19628514
OWN - NLM
STAT- MEDLINE
DCOM- 20091215
LR  - 20220409
IS  - 1538-5744 (Print)
IS  - 1538-5744 (Linking)
VI  - 43
IP  - 5
DP  - 2009 Oct-Nov
TI  - Intra-arterial transplantation of adult bone marrow cells restores blood flow and 
      regenerates skeletal muscle in ischemic limbs.
PG  - 433-43
LID - 10.1177/1538574409335158 [doi]
AB  - OBJECTIVE: Bone marrow cell therapy promotes angiogenesis, but the cellular fate 
      of bone marrow cells (BMCs) in the absence of immunosuppressant interventions is 
      unclear. We created a model of severe hind limb ischemia to address whether BMCs 
      form new blood vessels or differentiate into other tissues. METHODS AND RESULTS: 
      After ligating the common femoral artery in ApoE knockout mice, we injected 
      either phosphate buffered saline (PBS) or 5 x 10(7) adult unfractionated BMCs 
      obtained from green fluorescent protein-positive mice. Laser Doppler imaging of 
      the ischemic limbs revealed that intra-arterial BMCs significantly increased 
      blood flow recovery in ischemic limbs beginning 21 days after surgery and peaking 
      at 27 days (61.8% +/- 15% vs. 41.9% +/- 13.9%, respectively, for BMCs and PBS, P 
      < .05). The BMCs differentiated into small blood vessels, skeletal myofibers, and 
      supporting membranes, and these changes were associated with increased serum 
      levels of vascular endothelial growth factor (VEGF), fibroblast growth factor 2 
      (FGF-2), transforming growth factor beta (TGFbeta), interleukin 4 (IL-4), and 
      tumor necrosis factor alpha (TNF-alpha). CONCLUSIONS: Adult BMCs injected into 
      ischemic limbs without immunosuppressant therapy differentiated into blood 
      vessels and skeletal myofibers, and this was associated with accelerated blood 
      flow restoration and increased serum levels of VEGF, FGF-2, TGF-beta, IL-4, and 
      TNF-alpha. Skeletal muscle formation may provide benefits beyond angiogenesis to 
      patients with chronic peripheral arterial disease or to patients with low cardiac 
      output states who also suffer from skeletal muscle atrophy.
FAU - Liu, Qi
AU  - Liu Q
AD  - Wafic Said Stem Cell and Gene Therapy Research Laboratory, Texas Heart Institute 
      at St Luke's Episcopal Hospital, Houston, Texas.
FAU - Chen, Zhiqiang
AU  - Chen Z
FAU - Terry, Toya
AU  - Terry T
FAU - McNatt, Janice M
AU  - McNatt JM
FAU - Willerson, James T
AU  - Willerson JT
FAU - Zoldhelyi, Pierre
AU  - Zoldhelyi P
LA  - eng
PT  - Journal Article
DEP - 20090723
PL  - United States
TA  - Vasc Endovascular Surg
JT  - Vascular and endovascular surgery
JID - 101136421
RN  - 0 (Cytokines)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/*physiology
MH  - *Bone Marrow Transplantation/methods
MH  - Cell Differentiation
MH  - Cytokines/blood
MH  - Hindlimb
MH  - Injections, Intra-Arterial
MH  - Ischemia/physiopathology/*therapy
MH  - Laser-Doppler Flowmetry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Skeletal/*blood supply/physiology
MH  - *Neovascularization, Physiologic
MH  - *Regeneration
EDAT- 2009/07/25 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/07/25 09:00
PHST- 2009/07/25 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - 1538574409335158 [pii]
AID - 10.1177/1538574409335158 [doi]
PST - ppublish
SO  - Vasc Endovascular Surg. 2009 Oct-Nov;43(5):433-43. doi: 10.1177/1538574409335158. 
      Epub 2009 Jul 23.