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Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells : a pilot study and a randomised controlled trial . BACKGROUND Preclinical studies have established that implantation of bone marrow-mononuclear cells , including endothelial progenitor cells , into ischaemic limbs increases collateral vessel formation . We investigated efficacy and safety of autologous implantation of bone marrow-mononuclear cells in patients with ischaemic limbs because of peripheral arterial disease . METHODS We first did a pilot study , in which 25 patients ( group A ) with unilateral ischaemia of the leg were injected with bone marrow-mononuclear cells into the gastrocnemius of the ischaemic limb and with saline into the less ischaemic limb . We then recruited 22 patients ( group B ) with bilateral leg ischaemia , who were randomly injected with bone marrow-mononuclear cells in one leg and peripheral blood-mononuclear cells in the other as a control . Primary outcomes were safety and feasibility of treatment , based on ankle-brachial index ( ABI ) and rest pain , and analysis was per protocol . FINDINGS Two patients were excluded from group B after randomisation . At 4 weeks in group B patients , ABI was significantly improved in legs injected with bone marrow-mononuclear cells compared with those injected with peripheral blood-mononuclear cells ( difference 0.09 [ 95 % CI 0.06-0.11 ] ; p < 0.0001 ) . Similar improvements were seen for transcutaneous oxygen pressure ( 13 [ 9-17 ] ; p < 0.0001 ) , rest pain ( -0.85 [ -1.6 to -0.12 ] ; p=0.025 ) , and pain-free walking time ( 1.2 [ 0.7-1.7 ] ; p=0.0001 ) . These improvements were sustained at 24 weeks . Similar improvements were seen in group A patients . Two patients in group A died after myocardial infarction unrelated to treatment . INTERPRETATION Autologous implantation of bone marrow-mononuclear cells could be safe and effective for achievement of therapeutic angiogenesis , because of the natural ability of marrow cells to supply endothelial progenitor cells and to secrete various angiogenic factors or cytokines .
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Intervention_Physical
autologous transplantation of bone-marrow cells :
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Intervention_Physical
autologous implantation of bone marrow-mononuclear cells
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Intervention_Physical
injected with bone marrow-mononuclear cells into the gastrocnemius of the ischaemic limb and with saline into the less ischaemic limb
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Intervention_Physical
injected with bone marrow-mononuclear cells in one leg and peripheral blood-mononuclear cells in the other as a control
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Intervention_Physical
bone marrow-mononuclear cells
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Intervention_Physical
peripheral blood-mononuclear cells
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Intervention_Physical
Autologous implantation of bone marrow-mononuclear cells
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Outcome_Physical
Therapeutic angiogenesis
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Outcome_Physical
collateral vessel formation
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Outcome_Other
efficacy and safety
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Outcome_Other
safety and feasibility of treatment
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Outcome_Physical
ankle-brachial index ( ABI )
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Outcome_Pain
rest pain
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Outcome_Physical
ABI
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Outcome_Physical
transcutaneous oxygen pressure
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Outcome_Pain
rest pain
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Outcome_Pain
pain-free walking time
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Outcome_Mortality
died after myocardial infarction
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Outcome_Other
safe and effective
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Outcome_Physical
therapeutic angiogenesis