自体外周血单个核细胞治疗下肢缺血的优势及与疗效的相关分析
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摘要
目的：通过对59例下肢缺血性疾病患者进行自体外周血单个核细胞移植术,并分析影响疗效的移植细胞的种类、移植细胞的数量、移植细胞的浓度、移植时机、影响细胞植入后存活和增殖的因素,进一步指导病种选择、细胞种类及数量、移植时机等方面的临床应用；方法：对所有患者进行治疗前各症状评分,而后动员并采集外周血单个核细胞,于缺血下肢肌肉丰厚处多位点等间距注射,评价治疗后第7天及远期治疗效果并评分,分别比较CD34+细胞和单个核细胞与疗效的相关性,并统计与疗效的关系公式,分析单个核细胞浓度与疗效的相关性并统计两者之间的关系公式,比较糖尿病性下肢缺血与非糖尿病性下肢缺血的疗效,比较动脉低位阻塞和动脉高位阻塞患者的疗效,分析年龄、白细胞、单个核细胞的相关性,分析老年患者白细胞、中性粒细胞与单个核细胞的相关性并统计关系公式,分析特殊病种,重新评判适应症、禁忌症的范围,分析无效病例的原因；结果：单个核细胞移植术后,第7天及远期疗效均有不同程度的改善,总结各个影响疗效的因素发现,单个核细胞比CD34+细胞与疗效的相关性更强(尼莫地平值代表疗效),CD34+细胞数量与疗效的关系相关性为R=0.461(P=0.047),公式为尼莫地平值=0.484+1.055×CD34+细胞数,单个核细胞数量与疗效的关系相关性为R=0.473(P=0.000),公式为尼莫地平值=0.288+0.401×单个核细胞数；单个核细胞的浓度与疗效为直线正相关,相关性系数为R=0.421(P=0.002),公式为尼莫地平值=0.361+0.177×单个核细胞的浓度；糖尿病性下肢缺血与非糖尿病性下肢缺血的疗效无显著差异；动脉低位阻塞和动脉高位阻塞患者的疗效,除治疗后第7天静息痛和冷感前者改善更显著外,其他不同阶段的疗效无显著差异；所有患者的白细胞数量和单个核细胞数量呈直线正相关,R=0.315(P=0.015),公式为单个核细胞数=1.196+0.043×白细胞数,当排除多为中青年患者的血栓闭塞性脉管炎后,剩余病人多为老年患者,白细胞数与单个核细胞数的相关性R=0.500(P=0.000),公式为单个核细胞数=0.016+0.067×白细胞数,此组患者与全部患者相比,白细胞数与单个核细胞数的相关性更大,并且此组患者中性粒细胞数与单个核细胞数也有相关性,R=0.458(P=0.024),公式为单个核细胞数=0.005+0.063×中性粒细胞数；分析特殊病种发现,原发性血小板增多症患者、人工血管再栓塞患者应用单个核细胞移植术也能取得较好疗效；无效病例为伴有严重坏疽或伴有严重静脉血栓患者；结论：自体外周血单个核细胞悬液因含有多种不同阶段促血管新生的细胞,并因其微环境的优势,比移植纯化的内皮祖细胞(EPC)或CD34+细胞更有利于病情改善,对于糖尿病患者,即使EPC数量和功能下降,也能因单个核细胞悬液特有的优势收到同等的效果,对于适应症及禁忌症的范围也可重新考虑,病种的选择也可以逐步扩大至其他引起下肢缺血的疾病。
Objective:Having operated autologous peripheral blood mononuclear cells transplantation on 59 patients with lower limb ischemia and analyzed the factors affecting the therapeutic effects, such as species of transplanted cells, quantity of transplanted cells, concentration of transplanted cells, transplanting opportunity, survival and proliferation of transplanted cells after operation, suggest on clinical practice including determination of types of diseases, species and quantity of cells and transplanting opportunity, et al; Methods:Assessed and evaluated the symptoms of all the patients before the therapy, then injected the cells onto multiple points at muscle-rich body positions at equal intervals after mobilizing and collecting the peripheral mononuclear cells from all patients. Subsequently, assessed and evaluated the symptoms of all patients at the 7th day and follow-up period respectively. Compared the correlation of CD34+cells and mononuclear cells with the therapeutic effects, and drew the relative formula between the cells and the therapeutic effects; Analyzed the correlation between concentration of mononuclear cells and therapeutic effects, and drew the relative formula between them; Compared the therapeutic effects of diabetic lower limb ischemia with non-diabetic lower limb ischemia; Compared the therapeutic effects of low arterial obstruction and high arterial obstruction; Analyzed the correlation of age, white blood cells and mononuclear cells for all patients; Analyzed the correlation of age, white blood cells and mononuclear cells and drew the relative formula for elderly patients; Analyzed the special types of disease, assessed and evaluated the range of indications and contraindications; And analyzed the causes of invalid cases; Results:After the mononuclear cells transplantations, the therapeutic effects at the 7th day and follow-up period have been improved to some extent, all factors influencing the therapeutic effects have been summarized and depict that mononuclear cells have a higher correlation with therapeutic effect than CD34+cells (nimodipine values represent therapeutic effects); The correlation between CD34+cells and therapeutic effect was R=0.461 (P=0.047) based on the formula of nimodipine value=0.484+1.055×CD34+cells quantity; The correlation between mononuclear cells and therapeutic effects was R=0.473 (P=0.000) based on the formula of nimodipine value=0.288+0.401 xmononuclear cells quantity; The correlation between the concentration of mononuclear cells and therapeutic effects was R=0.473 (P=0.000) and the formula was nimodipine value=0.361+0.177×the concentration of mononuclear cells quantity; There was no remarkable difference in the therapeutic effects between diabetic lower limb ischemia and non-diabetic lower limb ischemia; Except for the more improved rest pain and cold sensation at 7th day in the low arterial obstruction group, there was no remarkable difference in the therapeutic effects between low and high arterial obstruction groups; For all patients, the correlation between the white blood cells quantity and mononuclear cells quantity was R=0.315(P=0.015) and the formula was mononuclear cells quantity=0.361+0.177×white blood cells quantity; Excluding the thrombosis phlebitis patients which were almost middle age and young persons, the rest patients were elderly people, the correlation between the white blood cells quantity and mononuclear cells quantity was R=0.500(P=0.000) based on the formula of mononuclear cells quantity=0.016+0.067×white blood cells quantity, comparatively the R value was higher than the average of all patients; For these elderly patients, the correlation between the neutrophil cells quantity and mononuclear cells quantity was R=0.458 (P=0.024), the formula was mononuclear cells quantity=0.005+0.063xneutrophil cells quantity; Through analyzing the special types of disease, mononuclear cells transplantation can also have therapeutic effects on essential thrombocythemia and secondary embolization after artificial vascular bypass surgery; And invalid cases were the complicated cases with severe gangrene or vein thrombosis. Conclusion:Autologous peripheral blood mononuclear cells suspension comprises of different stages of cells which can promote angiogenesis and has the niche advantage, so it may have better therapeutic effects than endothelial progenitor cells (EPC) and CD34+cells transplantation. Even for the diabetic patients who have decreasing quantity and quality of EPC, the same effect is achievable because of the special advantages of mononuclear cells. In addition, the range of indications and contraindications is advisably to be re-assessed and re-determined and the types of disease applicable are suggested to extend to other diseases which lead to lower limb ischemia.
Objective:Having operated autologous peripheral blood mononuclear cells transplantation on 59 patients with lower limb ischemia and analyzed the factors affecting the therapeutic effects, such as species of transplanted cells, quantity of transplanted cells, concentration of transplanted cells, transplanting opportunity, survival and proliferation of transplanted cells after operation, suggest on clinical practice including determination of types of diseases, species and quantity of cells and transplanting opportunity, et al; Methods:Assessed and evaluated the symptoms of all the patients before the therapy, then injected the cells onto multiple points at muscle-rich body positions at equal intervals after mobilizing and collecting the peripheral mononuclear cells from all patients. Subsequently, assessed and evaluated the symptoms of all patients at the 7th day and follow-up period respectively. Compared the correlation of CD34+cells and mononuclear cells with the therapeutic effects, and drew the relative formula between the cells and the therapeutic effects; Analyzed the correlation between concentration of mononuclear cells and therapeutic effects, and drew the relative formula between them; Compared the therapeutic effects of diabetic lower limb ischemia with non-diabetic lower limb ischemia; Compared the therapeutic effects of low arterial obstruction and high arterial obstruction; Analyzed the correlation of age, white blood cells and mononuclear cells for all patients; Analyzed the correlation of age, white blood cells and mononuclear cells and drew the relative formula for elderly patients; Analyzed the special types of disease, assessed and evaluated the range of indications and contraindications; And analyzed the causes of invalid cases; Results:After the mononuclear cells transplantations, the therapeutic effects at the 7th day and follow-up period have been improved to some extent, all factors influencing the therapeutic effects have been summarized and depict that mononuclear cells have a higher correlation with therapeutic effect than CD34+cells (nimodipine values represent therapeutic effects); The correlation between CD34+cells and therapeutic effect was R=0.461 (P=0.047) based on the formula of nimodipine value=0.484+1.055×CD34+cells quantity; The correlation between mononuclear cells and therapeutic effects was R=0.473 (P=0.000) based on the formula of nimodipine value=0.288+0.401 xmononuclear cells quantity; The correlation between the concentration of mononuclear cells and therapeutic effects was R=0.473 (P=0.000) and the formula was nimodipine value=0.361+0.177×the concentration of mononuclear cells quantity; There was no remarkable difference in the therapeutic effects between diabetic lower limb ischemia and non-diabetic lower limb ischemia; Except for the more improved rest pain and cold sensation at 7th day in the low arterial obstruction group, there was no remarkable difference in the therapeutic effects between low and high arterial obstruction groups; For all patients, the correlation between the white blood cells quantity and mononuclear cells quantity was R=0.315(P=0.015) and the formula was mononuclear cells quantity=0.361+0.177×white blood cells quantity; Excluding the thrombosis phlebitis patients which were almost middle age and young persons, the rest patients were elderly people, the correlation between the white blood cells quantity and mononuclear cells quantity was R=0.500(P=0.000) based on the formula of mononuclear cells quantity=0.016+0.067×white blood cells quantity, comparatively the R value was higher than the average of all patients; For these elderly patients, the correlation between the neutrophil cells quantity and mononuclear cells quantity was R=0.458 (P=0.024), the formula was mononuclear cells quantity=0.005+0.063xneutrophil cells quantity; Through analyzing the special types of disease, mononuclear cells transplantation can also have therapeutic effects on essential thrombocythemia and secondary embolization after artificial vascular bypass surgery; And invalid cases were the complicated cases with severe gangrene or vein thrombosis. Conclusion:Autologous peripheral blood mononuclear cells suspension comprises of different stages of cells which can promote angiogenesis and has the niche advantage, so it may have better therapeutic effects than endothelial progenitor cells (EPC) and CD34+cells transplantation. Even for the diabetic patients who have decreasing quantity and quality of EPC, the same effect is achievable because of the special advantages of mononuclear cells. In addition, the range of indications and contraindications is advisably to be re-assessed and re-determined and the types of disease applicable are suggested to extend to other diseases which lead to lower limb ischemia.
引文
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