Therapeutic angiogenesis using autologous bone marrow stromal cells: Improved blood flow in a chronic limb ischemia model
Therapeutic angiogenesis using autologous bone marrow stromal cells: Improved blood flow in a chronic limb ischemia model
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DOI：
10.1016/s0003-4975(02)04291-1
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发表时间：
2003-01-01
影响因子：
4.6
通讯作者：
Lachapelle, K
中科院分区：
文献类型：
--
作者：
Al-Khaldi, A;Al-Sabti, H;Lachapelle, K
背景评价了自体骨髓基质细胞移植的效果。在慢性肢体缺血的动物模型中，观察骨髓间充质干细胞（MSCs）对新生血管形成和血流的影响。通过结扎雄性刘易斯大鼠的左髂总动脉来产生慢性后肢缺血。结扎后3周，将500万LacZ（+）MSC（n = 10）或培养液（n = 10）注射到左大腿前内侧肌间室中。在注射后4周和6周，每组中一半动物（n = 5）接受缺血和非缺血肢体的股动脉超声血流测量，以获得流量比。动物还接受血管造影术和血管密度和小动脉密度的测量。对肢体肌肉进行定性组织学评估。LacZ（+）MSCs可分化为内皮细胞。（FVIII+）、血管平滑肌（α-平滑肌肌动蛋白阳性）、骨骼肌（结蛋白阳性）和脂肪细胞。植入MSC的缺血后肢具有比对照肢体更大的血管密度和小动脉密度（p < 0.001）。在第4周和第6周测量的注射MSC的大鼠的股动脉血流指数（左股动脉血流/右股动脉血流）分别为0.89 +/- 0.12和0.90 +/- 0.06，而对照大鼠为0.50 +/- 0.15和0.50 +/- 0.10（p < 0.001）。血管造影显示，通过盆腔和腹壁侧支形成，接受MSC植入的大鼠左股动脉重建。“结论。局部MSC植入诱导新生血管反应，导致流向缺血肢体的血流显著增加。骨髓基质细胞也能够自发地再生肌肉组织的各种成分。(C)2003年由胸外科医师协会发布。
Background. We evaluated the effect of autologous marrow stromal. cells (MSCs) on neovascularization and blood flow in an animal model of chronic limb ischemia.Methods. Chronic hind limb ischemia was created by ligating the left common iliac artery of male Lewis rats. Three weeks after ligation, 5.0 million LacZ(+)MSCs (n = 10) or culture medium (n = 10) were injected into the anteromedial muscle compartment of the left thigh. At 4 and 6 weeks after injection, half the animals (n = 5) from each group underwent femoral artery ultrasonic blood flow measurements of the ischemic and nonischemic limbs to obtain a flow ratio. The animals also underwent angiography and measurements of blood vessel density and arteriolar density. Qualitative histologic assessment of the limb muscles was performed.Results. LacZ(+)MSCs were found to differentiate into endothelium. (F VIII+), vascular smooth muscle (positive a-smooth muscle actin), skeletal muscle (positive desmin), and adipocytes. Ischemic hind limbs where MSCs were implanted had greater vascular density and arteriolar density than control limbs (p < 0.001). Femoral artery flow index (left femoral artery flow/right femoral artery flow) was 0.89 +/- 0.12 and 0.90 +/- 0.06 for rats injected with MSCs measured at 4- and 6-weeks, respectively, compared with 0.50 +/- 0.15 and 0.50 +/- 0.10 for the control rats (p < 0.001). Angiography demonstrated reconstitution of the left femoral artery in rats that received MSC implantation through pelvic and abdominal wall collateral formation. ' Conclusions. Local MSC implantation induces a neo-vascular response resulting in a significant increase in blood flow to the ischemic limb. Marrow stromal cells are also capable of spontaneously regenerating the various components of muscular tissues. (C) 2003 by The Society of Thoracic Surgeons.