Print this pageEnhanced Mobilization of Mononuclear Cells by G-CSF Reduces the Volume of Bone Marrow Needed to Induce Angiogenesis in Lower Limb Ischemia.
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Yong-Quan Gu*1, Y F Wu*1, J Zhang*1, L X Qi*1, J X Li*1, L R Guo*1, S W Zhang*1, Z G Wang*1, Yu Hong*2, Darwin Eton3
1Xuan Wu Hospital, Capital Medical University, Beijing, China; 2University of Miami, Miami, FL; 3University of Miami and the Miami VA, Miami, FL
Background: To determine if human granulocyte colony-stimulating factor (G-CSF) can reduce the volume of bone marrow (BM) needed to isolate sufficient mononuclear cells (MNC) for implantation in ischemic lower limbs to promote angiogenesis.
Methods: 145 ischemic limbs in 129 patients (aged 70.4 ±4.7 years, 64% male) were injected with autologous BM-MNC. Associated diseases included diabetes (88%) and thromboangitis obliterans (5%). Patients with severe coronary artery disease or renal failure were excluded. Group 1 patients (N=35, 43 limbs) were pre-treated with G-CSF 300µg/day IV for 2 days. Group 2 patients were not (N=94, 102 limbs). Both groups had similar demographics. Presenting limb symptoms were gangrene (Gp1 N=7 limbs, Gp2 N=22), ischemic ulcer (Gp1 N=12, Gp2 N=23), ischemic rest pain (Gp1 N=19, Gp2 N=41), and claudication (Gp1 N=5, Gp2 N=13). BM-MNC were isolated by gradient density centrifugation from bone marrow aspirated from the iliac crest. The patients were re-evaluated two months after injection of the BM-MNC into the ischemic limb.
Results: G-CSF increased the circulating WBC to 23,000/mm3 (range 15,000-38,000/mm3) and significantly enhanced the BM-MNC yield. Only half the amount of marrow was harvested from Gp1 (196 ± 17ml) versus Gp2 (377 ± 39 ml) patients, and yet the total MNC yield was 5.6±2.1 ×109 cells in Gp1 versus only 1.0±0.9 ×109 in Gp2 (P<0.001). This represented a 10.8 fold increase in MNC per ml of BM harvested. Two months following implantation, transcutaneous oxygen pressure (TcPO2) increased in 92 % of Gp1 limbs vs 87 % of Gp2 (NS) , with a trend in the increase favoring Gp1 patients (see table). Ulcer healing rates were 73% in Gp2 and 70% in Gp1 (NS). The major amputation rate was 5% in Gp1 and 13% in Gp2 (p<.05). Improvement in subjective symptoms (pain, coldness, or numbness) was 95% in Gp1 and 84% in Gp 2 (p=0.01).
| TcPO2 Increase | Gp1: G-CSF | Gp2 |
| (mmHg) | 82 limbs | 39 limbs |
| >20 | 28% | 15% |
| 10-19 | 23% | 26% |
| 5-9 | 21% | 31% |
| 1-4 | 21% | 17% |
| 0 | 8% | 11% |
| ∑ =100% | ∑ =100% |
Conclusion: G-CSF increased the yield of BM-MNC 10.8 fold per ml of BM harvested. Clinical evidence of angiogenesis was positively influenced despite the smaller volume of marrow harvested. G-CSF enhances the efficacy of this angiogenesis strategy.
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