Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model
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Background: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model.
Methods: We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n=20) or saline was injected as a control group (n=20). LBF was measured using an electromagnetic flowmeter. A total of 106 MSCs were implanted into each ischemic limb.
Results: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar.
Conclusions: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.
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Thesis or Dissertation
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Shinsuke Mikami, Ayumu Nakashima, Keigo Nakagawa, Tatsuya Maruhashi, Yumiko Iwamoto, Masato Kajikawa, Takeshi Matsumoto, Yasuki Kihara, Kazuaki Chayama, Kensuke Noma, Mitsuo Ochi, Masahiro Nishimura, Koichiro Tsuji, Yukio Kato, Chikara Goto, Yukihito Higashi; Autologous Bone-Marrow Mesenchymal Stem Cell Implantation and Endothelial Function in a Rabbit Ischemic Limb Model; PLoS ONE 8(7): e67739. (doi: 10.1371/journal.pone.0067739)
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Philosophy in Medical Science
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Graduate School of Biomedical Science