Objective To investigate the effectiveness of autologous bone marrow mononuclear cells transplantation on lower l imb chronic venous ulcer. Methods Between May 2009 and September 2010, 17 patients with lower l imb chronic venous ulcer were treated with autologous bone marrow mononuclear cells transplantation (transplantation group) and 10patients treated without cells transplantation served as control group. In the transplantation group, there were 9 males and 8 females with age of (33.3 ± 6.1) years, including 11 cases of simple great saphenous vein varicosity and 6 cases of chronic venous insufficiency; the area of ulcer was (4.39 ± 2.46) cm2; and the duration of ulcer ranged from 3 months to 6 years. In the control group, there were 4 males and 6 females with age of (39.2 ± 10.3) years, including 7 cases of simple great saphenous vein varicosity and 3 cases of chronic venous insufficiency; and the area of ulcer was (5.51 ± 2.63) cm2; and the duration of ulcer ranged from 3 months to 2 years. All patients in both groups were classified as C6 according to Cl inical Etiology Anatomy Pathophysiology (CEAP) classification. No signficant difference was found in the general data between 2 groups (P gt; 0.05). The heal ing process of ulcer was observed. The granulation tissue was harvested for HE staining before operation and at 3 days after operation in the transplantation group. The microvessel density (MVD) and vascular endothel ial growth factor (VEGF) expression of ulcer granulation tissue were observed. Results In the transplantation group, ulcer heal ing was accelerated; complete heal ing was observed in 15 cases, partial heal ing in 1 case, and no heal ing in 1 case with the median heal ing time of 22 days. However, in the control group, the heal ing process was slower; complete heal ing of ulcer was observed in 7 cases and no heal ing in 3 cases with the median heal ing time of 57.5 days. There was significant difference in the heal ing time between 2 groups (Z=0.001 4, P=0.002 7). HE staining showed a great number of microvessels in the granulation tissue in the transplantation group. The immunohistochemical staining showed that MVD was significantly increased (t=3.120, P=0.008) after cell ransplantation (32.1 ± 12.8) when compared with that before transplantation (22.1 ± 6.7). The VEGF expressionafter transplantation (8.05% ± 5.10%) was increased sl ightly when compared with that before transplantation (6.13% ±4.20%), but the difference was not significant (t=1.150, P=0.268). Conclusion Autologous bone marrow mononuclear cellstransplantation can stimulate granulation tissue growth and improve ulcer heal ing.
Objective To investigate the efficacy of autologous bone marrow mononuclear cells transplantation in treating lower l imb thromboangiitis obl iterans (TAO). Methods From January 2005 to November 2008, 25 patients (27 l imbs) with lower l imb TAO were treated. There were 24 males (26 l imbs) and 1 female (1 l imb), aging 16-44 years (33 years on average). Fifteen left l imbs and 12 right l imbs were involved. The median duration of disease was 2 years (from 3 months to9 years). Intermittent claudication was observed in 5 cases (5 l imbs), 16 patients (17 l imbs) had symptom of rest pain, 4 patients (5 l imbs) suffered ulcer on the distal l imbs. The results of visual analogue scale (VAS), maximum walking distance (MWD), ankle/brachial index (ABI), and transcutaneous oxygen pressure (TcPO2) before operation were (7.16 ± 1.12) points, (0.098 ± 0.043) km, 0.20 ± 0.09, and (11.78 ± 3.46) mm Hg (1 mm Hg=0.133 kPa), respectively. A total of 300 mL bone-marrow blood was extracted from the il iac bone. And then the mononuclear cells were isolated from the bone-marrow blood. All patients received cell transplantation only one time. The amount of transplantation bone marrow mononuclear cells was (1.82-29.46) × 109 (mean 13.33 × 109). Results All patients were followed up for 1 years. After 4 weeks of implantation, the results of VAS, MWD, ABI, and TcPO2 were (2.39 ± 0.51) points, (0.783 ± 0.176) km, 0.28 ± 0.16, (21.33 ± 6.57) mm Hg, respectively, showing significant difference compared with preoperative results (P lt; 0.05). The VAS, MWD, ABI, and TcPO2 increased to (2.44 ± 0.67) points, (1.199 ± 0.304) km, 0.37 ± 0.09, (27.90 ± 5.23) mm Hg after 1 year of implantation, showing significant differences compared with preoperative results (P lt; 0.05). One ulcer healed well and the improvement was obtained in other 3 cases after 4 weeks of implantation (80%). Four ulcers healed well after 1 year of implantation (80%). After 1 year of implantation, angiography revealed 37.04% affected limbs had a satisfactory neovascularization. The angiographic levels were grade 0 in 5 cases, grade 1 in 12 cases, grade 2 in 4 cases, and grade 3 in 6 cases. Conclusion Autologous bone marrow mononuclear cells transplantation could be a simple, safe, effective method to treat TAO.
Objective To explore the middle-term outcome of autologous bone marrow mononuclear cells transplantation in the treatment of lower l imb ischemia. Methods From March 2003 to June 2005, 65 patients with lower l imb ischemia were treated by autologous bone marrow mononuclear cells transplantation. Of the patients, there were 50 males and 15 females, with a mean age of 66.5 years (range 36-89 years), including 4 cases of simple arteriosclerotic occlusion,5 cases of thromboangiitis obl iterans and 56 cases diabetic lower l imb ischemia. A total of 400 mL bone-marrow blood were extracted from the posterior superior il iac crest. And then the mononuclear cells were isolated from the bone-marrow blood in the laboratory. The amount of transplantation bone marrow mononuclear cells was (0.60-1.80) × 109 (mean 1.05 × 109). Twelve patients received cell transplantation from two to four times and the other patients one time. According to the improvement of cl inical finding, the outcome was evaluated. Results All the patients were followed up for 8-56 months (mean 21.5 months). There were 8 deaths, and the mortal ity was 12.3%; 5 were due to myocardial infarction and heart failure and 3 were due to cerebral infarction. The general effective rate was 70.8% (46/65) and the recurrent rate was 10.7% (7/65). Of them, the response to treatment lasted over 12 months in 42 cases, accounting for 91.3% (42/46); over 24 months in 24 cases, accounting for 52.2% (24/46); and over 37 months in 12 cases, accounting for 26.1% (12/46). The effective rates were 100% in 12 patients who received 2-4 times transplantation and 64.2% in 53 patients who received 1 time transplantation, showing statistically significant difference between them (P lt; 0.001). Conclusion The middle-term outcome of autologous bone marrow mononuclear cells transplantation show that it is a feasible and simple method for treatment of lower l imb ischemia.
Objective To investigate the cl inical appl ication of grafting with bioactive glass (BG) and autologousbone marrow for defect after resection and curettage of benign bone neoplasm. Methods From January 2004 to May2007, 34 patients with bone defects were repaired. There were 21 males and 13 females with a mean age of 25.6 years (8 to 56 years). There were 14 cases of simple bone cysts, 6 cases of fibrous dysplasia, 3 cases of osteoid osteoma, 4 cases of non-ossifying fibroma, 2 cases of enchondroma and 3 cases of giant cell tumor of bone. Tumor sizes varied from 2.0 cm × 1.5 cm × 1.0 cm to 9.0 cm × 3.0 cm × 2.5 cm. Benign bone neuplasm was removed thoroughly with a curet or osteotome, bone defects ranged from 3.0 cm × 2.0 cm × 1.5 cm to 11.0 cm × 3.5 cm × 3.0 cm, which was closed-up with the mixtures of BG and autogenous red bone marrow. Six cases of pathologic fracture were fixed with steel plate or intramedullary nail. The postoperative systemic and local reactions were observed, and the regular X-ray examinations were performed to observe the bone heal ing. Results All the patients had good wound heal ing after operation. There was no yellow effusion nor white crystal and skin rash appeared around wound, indicating no allergic reaction occurred. A follow-up of 1 to 4 years (mean 24.6 months) showed satisfactory heal ing without compl ications. At averaged 16 weeks after operation, patients with bone tumor in lower l imbs resumed walking independently and those with bone tumor in upper l imbs resumed holding object. There was no tumor recurrence during follow-up. Radiographically, the interface between the implanted bone and host bone became fuzzy 1 month after implantation. Two months after operation, the BG was absorbed gradually, new bone formation could be seen in the defects. Four months after operation, implanted bone and host bone merged together, bone density increased. Six to ten months after operation, the majority of the implanted BG was absorbed and substituted for new bone, bone remodel ing was establ ished. Conclusion BG may boast both bone conductive and bone inductive activities. The combined grafting with BG and autologous bone marrow appears to be minimally invasive treatment to repair bone defects of benign bone neuplasm, with rare compl ications and no significant reverse reaction, and could repair bone defects completely.
Objective To investigate the clinical result of treatment of bonecyst by transplantation of the autologous bone marrow combined with the allograft bone. Methods From February 2004 to March 2006, 13 patients withbone cyst were treated by transplantation of the autologous bone marrow combined the the allograft bone. Among the 13 patients, 6 were males and 7 were females, ranging in age from 5 to 16 years, averaged 11.5 years. In the patients, 5 lesions were located inthe proximal humerus, 2 in the femoral neck, 3 in the femoral shaft, 2 in the proximal tibia, and 1 in the distal tibia. Among the patients, 5 had a complication of pathologic fracture. All the patients underwent an erasion of the bone cyst, and then the transplantation of the autologous bone marrow combined with the allograft bone, and 8 of them were also given an instrument fixation. Results The follow-up for 6 months to 2 years after operation revealed that 5 of the patients had an incision healing by the first intention, 5 had an effusion in the incision site, and 3 had a delayed healing of the incision. According to the Capanne criteria, the postoperative X-ray findings indicated that 10 patients had Grade Ⅰ healing, and 3 had Grade Ⅱ healing. The complete healing took 3.5-8 months,averaged 5.2 months. There was no recurrence. When the fixation instrument was removed, no pathologic fracture occurred. The function of the upper and lower limbs recovered. Conclusion Transplantation of the autologous bone marrow combined with the allograft bone is an effective and safe procedure for treatment of bone cyst.
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.
Objective To explore the effective autologous bone marrow stem cell dosage for treatment of severe lower limb ischemia. Methods From December 2003 to December 2004, 22 cases of bilateral lower limb ischemia were treated with autologous bone morrow cell transplantation. All the patients were randomly divided into two groups according to ischemia degree. In group A(severe ischemia side), the amount of transplanted autologous bone marrow cells was more than 1×108, and ingroup B(mild ischemia side), the amount was less than 1×105. A series of subjective indexes, such as improvement of pain, cold sensation and numbness, and objective indexes, such as increase of ankle/brachial index (ABI) and transcutaneous oxygen pressure (TcPO2), angiography, amputation rate, and improvement of foot wound healing were used to evaluate the effect of autologous bone marrow stem cells implantation. Results The rates of pain relief were 90.0% in group A and 16.7% in group B (Plt;0.01); the rates of cold sensation relief were 90.5% in group A and 5.3% in group B（Plt;0.01）;the improvement of numbness was 62.5% in group A and 9.1% in group B（Plt;0.01）. Increase of ABI was 31.8% and 0 in groups A and B respectively（Plt;0.01） at 4 weeks after implantation. Increase of TcPO2was 94.4% and 11.1% in groups A and B respectively（Plt;0.01） at 4 weeks after implantation. Twelve cases of angiography showed rich new collateral vessels in 100% of the limbs in group A while no remarkable new collateral vessel in group B. The amputation rates were 4.5% in group A and 27.3% in group B（Plt;0.05） at 4 weeks after implantation. The rate of improvement of foot wound healing was 75% in group A and there was no changein wound healing in group B after 4 weeks of implantation. Conclusion The effectiveness of autologous bone marrow stem cell implantation depends on the number of implanted stem cells. Effectiveness is expected in most patients if the implanted stem cell is more than 1×108, whereas there would be little effect if the cell number is less than 1×105.
Objective To evaluate the therapeutic results of percutaneous injection of autogeous bone marrow for simple bone cyst and to analyze the prognostic factors of the treatment. Methods From March 2000 to June 2005, 31 patients with simple bone cysts were treated by percutaneous injection of autogeous bone marrow. Of 31 patients, there were 18 males and 13 females, aged 5 years and 7 months to 15 years. The locations were proximal humerus in 18 cases ,proximal femur in 7 cases and other sites in 6 cases. Two cases were treated with repeated injections. The operative process included percutaneous aspiration of fluid in the bone cysts and injection of autogenous bone marrow aspirated fromposterior superior iliac spine. The mean volume of marrow injected was 40 ml(30-70 ml).Results No complications were noted during treatment. Thirty patients were followed for an average of 2.2 years(1.5 years) with 2 cases out of follow-up. After one injection of bone marrow, 9 cysts(29.0%) were healed up completely, 7 cysts(226%)basically healed up,13 cysts (41.9%)healed up partially and 2 (6.5%) had no response.The satisfactory and effective rates were 67.7% and 93.5% respectively. There was significant difference between active stagegroup and resting stage group(P＜0.05). There were no statistically significant difference in therapeutic results between groups of different ages, lesion sites or bone marrow hyperplasia(Pgt;0.05). Conclusion Percutaneous injection of autogeous bone marrow is a safe and effective method to treat simple bone cyst, but repeated injections is necessary for some patients. The therapeutic results are better in cysts at resting stage than those at active stage.