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Ann Thorac Surg 2003;75:204-209
© 2003 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, McGill University, Montreal, Quebec, Canada
b Lady Davis Institute for Medical Research, McGill University Health Center, Montreal, Quebec, Canada
Accepted for publication August 12, 2002.
* Address reprint requests to Dr Lachapelle, Royal Victoria Hospital, 687 Pine Avenue W, Suite S8.30, Montreal, QB, H3A 1A1, Canada
e-mail: klacha1{at}po-box.mcgill.ca
Presented at the Poster Session of the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.
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 
-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 neovascular 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.
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