Objective To observe the clinical efficiency of the implantation of the autologous bone marrow mononuclear cells for treatment of lower limb ischemia after the bone marrow stimulation. Methods From May to December 2005, 43 ischemic limbs in 35 patients (23 males,12 females; aged 3490 years,averaged 71.3 year) were treated. Of the 35 patients, 30 had diabetic lowerlimb ischemia with 38 lower ischemic limbs, 2 had atherosclerosis obliterans with 2 ischemic lower limbs, and 3 had thromboangiitis obliterans with 3 ischemic lower limbs. Five patients with 5 ischemic limbs were in stage Ⅰ lower limb ischemia (intermittentclaudication), 15 patients with ischemic 19 limbs were in stage Ⅱ (rest pain),9 patients with 12 ischemic limbs were in stage Ⅲa(ulceration), and 6 patients with 7 ischemic lower limbs in stage Ⅲb (gangrene); 88.4% of all the ischemic lower limbs （38/43）had a pain, 79.1%（34/43） had coldness, and 69.8%（30/43）had limb numbness. The bone marrow of each patient was stimulated by an injection of the recombinant human granulocyte-macrophage colony-stimulatory factor 300 μg/d for 2-3 days. The bone marrow 130-200 ml was drawn from the iliac spine and the mononuclear cells were obtained. Each patient received implantation of the autologous bone marrow mononuclear cells by an intramuscular injection, an arterial intraluminal injection or a combined injection of the two routes.Results The pain relief was found in 94.7% of theischemic lower limbs, and pain improvement in 97.1% . Relived numbness was found in 93.3%. The distance of the claudication was increased by all the ischemic limbs. An increase in the ankle/ brachial index (ABI)was found in 47.9%. The transcutaneous oxygen pressure (TcPO2) increased in 92.3%. The ulcer heal rate was 9.1% (1/11). Markedlyreduced ulcer wound was found in 27.3% (3/11). The amputation rate was 6.3% (3/48). Arterial angiography revealed that there was a new collateral vessel formationin 91.2%. Complications were as follows: fever and mild fatigue-developed respectively in 1 patient after the bone marrow stimulation, but relieved by themselves. Acute but mild myocardial infarction was found in 1 patient with a slight precordial pain and elevation of myocardial enzymes 1 week after transplantation of the bone marrow mononuclear cells, but recovered after medical treatment. The follow-up averaged 5 months. According to the subjective criteria, the overall efficacy was90%. ABI increased in 62.5% of the patients after operation and the value of TcPO2 was higher in 90% of the patients after this kind of therapy. Arterial angiography revealed a new collateral vessel formation in 90.5% of the 21 ischemic limbs. The foot ulcer healed in 7 and obviously improved in 3. Three of the foot ulcer patients were discharged 2-3 months after the amputation was performed on the diseased toes. Conclusion Implantation of the autologous bone marrow mononuclear cells after the bone marrow stimulation of treatment of the lower limb ischemia has advantages of less marrow aspiration, more mononuclear cell content, satisfactory shortterm effect, and relatively high safety. Itis a new method of treating the lower limb ischemia besides the autologous bone marrow and peripheral blood mononuclear cell implantation. The longterm effect of this method needs a further study.
ObjectiveTo systematically review the efficacy and safety of autologous mononuclear cells transplantation in osteonecrosis of the femoral head.MethodsPubMed, EMbase and The Cochrane Library were electronically searched to collect randomized and non-randomized controlled trials on autologous mononuclear cells transplantation for osteonecrosis of the femoral head from inception to July 31th, 2020. Two reviewers independently screened literatures, extracted data and assessed risk of bias of included studies. Meta-analysis was then performed using RevMan 5.4 software.ResultsA total of 17 studies involving 645 hips in mononuclear cells group and 557 hips in cell-free group were included. The results of meta-analysis showed that compared with cell-free therapy, mononuclear cells therapy could improve hip function in term of Hairrs score (MD=8.11, 95%CI 4.36 to 11.87, P<0.000 1), Merle D`Aubigné Postel score (MD=2.23, 95%CI 0.97 to 3.49, P=0.000 5), WOMAC score (MD=−10.81, 95%CI −15.80 to −5.81, P<0.000 1), Lequesne index (MD=−2.97, 95%CI −5.42 to −0.52, P=0.02) and alleviate the pain (MD=−9.13, 95%CI −12.40 to −5.86, P<0.000 01), delay the progression of radiological staging (RR=0.55, 95%CI 0.34 to 0.89, P=0.01) and reduce the rate of total hip arthroplasty (RR=0.61, 95%CI 0.43 to 0.86, P=0.005). In terms of safety, mononuclear cell therapy did not increase the rate of complications (RR=0.77, 95%CI 0.33 to 1.83, P=0.56).ConclusionsThe current evidence shows that autologous mononuclear cells therapy is a safe and effective way for osteonecrosis of the femoral head. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.