Intra-arterial injection of human embryonic stem cells in athymic rat hind limb ischemia model leads to arteriogenesis

Shear stress can enhance differentiation of human embryonic stem cells (hESC) to vascular cells. We tested the hypothesis that intra-arterial hESC injection will lead to arteriogenesis while intramuscular injection will have no effect on vascularization. Methods and Results: The superficial femoral arteries were excised on both hind limbs in athymic rats. hESC (2x10(6)) were injected intra-arterially (shear stress) or intramuscular (no shear stress) in one limb after arterial excision. Blood flow, muscle perfusion, and number of arteries/mm(2) muscle were studied at 10 and 21 days after injection. Blood flow in the common iliac artery improved significantly at 10 days after intra-arterial injection of hESC (22 +/- 9%, Pb. 02), and tight muscle perfusion improved significantly both at 10 and 21 days (9 +/- 2%, 16 +/- 5% respectively, both Pb. 02). In comparison, intramuscular injection of hESC did not affect blood flow at 10 and 21 days (-3 +/- 10% and 4 +/- 6%, respectively), while perfusion showed no significant effect of hESC injection after 10 days (1 +/- 8%) and was increased 21 days after hESC injection (11 +/- 5%, P=. 03). Arterial density did not improve after intra-arterial hESC injection at 10 days (15 +/- 13%, P=. 15) and significantly improved at 21 days (13 +/- 4%, Pb. 05). No significant change was demonstrated after intramuscular injection. Summary: Intra-arterial injection of hESC resulted in moderate improvement of flow and perfusion and increased number of arteries in the ischemic hind limb. No consistent change in perfusion, flow, and number of arteries was observed after intramuscular injection. (C) 2011 Elsevier Inc. All rights reserved.