Transient increase of cytokines in the acute ischemic tissue is beneficial to cell-based therapeutic angiogenesis

Background: Implantation of bone marrow cells (BMCs) is a treatment of ischemic disease. It is well known that many inflammatory cytokines are released in ischemic tissue, especially in the acute phase, so in the present study it was investigated if the transient increase of cytokines in the acute ischemic tissue influences cell-based therapeutic angiogenesis. Methods and Results: Ischemic limb models were created in C57BL/6 mice as 24 h (acute) or 2 weeks (chronic) after ischemia. BMCs were cultured with total tissue protein, which was extracted from the acute and chronic ischemic muscles. The survival, adhesion, and migration of BMCs were significantly better after culture with 1 mg/ml total tissue protein extracted from the acute ischemic limbs than from the chronic ischemic limbs (p<0.001). For the in-vivo study, 8×10 ⁶ BMCs, collected from green fluorescent protein (GFP) transgenic mice, were implanted into the acute or chronic ischemic limbs of the mice. The survival of implanted cells and blood flow were significantly better when BMCs were implanted into the acute ischemic limbs than into the chronic ischemic limbs (p<0.001). Conclusions: A transient increase of cytokines in the acute ischemic tissue is beneficial for cell-based therapeutic angiogenesis.