Randomised comparison of G-CSF-mobilized peripheral blood mononuclear cells versus bone marrow-mononuclear cells for the treatment of patients with lower limb arteriosclerosis obliterans

Abstract

Previous studies have suggested that the lower limb arteriosclerosis obliterans (LASO) could be improved by autologous transplantation of either bone marrow mononuclear cells (BM-MNC) or G-CSF-mobilized peripheral blood mononuclear cells (M-PBMNC). However, the number of patients observed was very limited, and little information is available regarding comparison. The present randomised trial was designed to assess which is the better option. One hundred fifty patients with LASO were randomised to either group A (76 cases implanted with M-PBMNC) or group B (74 cases implanted with BM-MNC), and followed up for 12 weeks. Primary outcomes were safety and efficacy of treatment, based on ankle-brachial index (ABI) and rest pain, and analysis was per protocol. Significant improvement of the main clinical index was observed in both groups after transplantation. No transplantation-related complication was observed in either group. Comparative analysis revealed that at 12 weeks after cell implantation, improvement of ABI (difference 0.06 +/- 0.01; p < 0.0001), skin temperature (difference 0.55 +/- 0.25; p = 0.028), and rest pain (difference -0.57 +/- -0.15;p < 0.0001) was significantly better in groupA patients than group B patients. However, there was no significant difference between two groups for pain-free walking distance, transcutaneous oxygen pressure, ulcers, and rate of lower limb amputation. Autologous transplantation of either M-PBMNC or BM-MNC significantly promotes improvement of limb ischaemia in patients with LASO. Comparative analysis indicated that M-PBMNC should be more practical in comparison with BM-MNC in the treatment of LASO.

Bone marrow mononuclear cells versus G-CSF-mobilized peripheral blood mononuclear cells for treatment of lower limb ASO: pooled analysis for long-term prognosis

“…Given that data on short-term efficacy in terms of rest pain, skin temperature, ABI and so on have been reported elsewhere, 17,22 in the future, the choice of cell therapy will be made according to factors such as time to benefit, the likelihood of avoiding pain and reducing ulcer size, the likely impact of invasive procedures during cell collection, the risk of adverse events and cost. Currently, cell collection and implantation of BMMNC and M-PBMNC are performed on an inpatient basis, but in the future, M-PBMNC therapy will be undertaken as an outpatient procedure.…”

“…In the past decade, many cell therapies for CLI have been developed. The types of therapeutic cells used till date have been bone marrow mononuclear cells (BMMNC), 2-11 PBMNC, 2,12,13 G-CSF-mobilized (M)-PBMNC, [14][15][16][17][18] CD34-antigen-positive mononuclear cells 19,20 and CD133-antigen positive cells. 21 Although BMMNC or M-PBMNC intramuscular implantation has been used most often, both therapies have some risk: to collect about 500 mL of BMMNC, general anesthesia of about 4 h duration is necessary, and to collect PBMNC, about 3 h of apheresis with G-CSF treatment is required.…”

“…21 Although BMMNC or M-PBMNC intramuscular implantation has been used most often, both therapies have some risk: to collect about 500 mL of BMMNC, general anesthesia of about 4 h duration is necessary, and to collect PBMNC, about 3 h of apheresis with G-CSF treatment is required. [2][3][4][5][6][7][8][9][10][11][14][15][16][17][18] In a first cell-therapy trial, results of which were published in 2002, 22 ASO patients (44 limbs) were implanted with either BMMNC or PBMNC. 2 At 6 months after implantation, both therapies yielded improvements in terms of rest pain, ABI and transcutaneous oxygen pressure, but the clinical outcomes for BMMNC were significantly better than those for PBMNC.…”

“…These authors observed that the BMMNC and G-CSF groups had significantly better outcomes than the control group with respect to ABI and transcutaneous oxygen pressure, and that there was no significant difference between the BMMNC and G-CSF groups with respect to ABI and transcutaneous oxygen pressure. In another randomized controlled trial, Huang et al 17 compared BMMNC and M-PBMNC for the treatment of ASO, and showed that both therapies yielded a benefit at 3 months after implantation, and that M-PBMNC produced significantly greater improvements than BMMNC with respect to rest pain, skin temperature and ABI. Recently, the result of a meta-analysis of 37 trials was reported.…”

Stem Cell Transplantation for the Treatment of Peripheral Arterial Disease

“…Similarly, 150 patients with PAD were randomised to PBMNC (n=76) or BMMNC (n=74) and followed for 12 weeks [20]. In the PBMNC group, improvements in ABI (p<0.0001), skin temperature (p=0.028), and rest pain (p<0.0001) were significantly more pronounced in comparison to the BMNC group [20]. However, no between-group difference was found in terms of pain-free walking distance, TcPO 2 , ulcers, and amputation rates.…”