Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Duchenne Muscular Dystrophy: Safety and Feasibility Study in India.
Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Duchenne Muscular Dystrophy: Safety and Feasibility Study in India.
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发表时间：
2015
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通讯作者：
B. Rajput;S. Chakrabarti;Vaishali S Dongare;C. Ramirez;K. Deb
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作者：
B. Rajput;S. Chakrabarti;Vaishali S Dongare;C. Ramirez;K. Deb
目的杜氏肌营养不良症（DMD）是一种以肌营养不良蛋白缺乏为特征的肌肉退行性疾病，目前尚无确切的治疗方法。废弃脐带是间充质干细胞的潜在来源，其无免疫原性，可用于同种异体移植。鉴于间充质干细胞（MSC）的再生和抗炎特性，我们在这里研究了其在DMD患者细胞治疗中的作用。设计：这是一项在印度孟买、德里和勒克瑙的多家医院进行的单盲研究。入选标准为5 ~ 18岁的男孩，肌肉活检免疫组化中无抗肌萎缩蛋白，细胞遗传学分析中抗肌萎缩蛋白基因突变。排除标准是肌肉活检中存在肌营养不良蛋白、使用皮质类固醇的患者等。通过IV和IM注射施用UC-MSC（2百万/kg体重）。对11例DMD患者移植UC-MSCs后的上肢近端、上肢远端、下肢近端、下肢远端、髋屈肌、髋伸肌、髋外展肌和椎旁肌的肌力进行测量，并随访3年（平均随访1.5年）。5例DMD患者未接受任何UC-MSCs移植，作为对照组。结果治疗组（N = 11）移植前上肢近端和远端肌肉肌力分别为3.45 ± 1.0357和4.090 ± 0.8312; 1年后（N = 9），这些强度保持稳定，平均值为3.78（1.03）和4.22（0.83）。相比之下，对照组（N = 5）在上肢近端和远端分别具有3.6（0.54）和4（1）的移植前强度。1年后，（N = 5）3/5例受试者的上肢近端轻微但无统计学显著性降低，平均3.0（1.0），5/5例受试者的力量降低lunit，平均3.0（1.0）。治疗组移植前下肢远、近端肌力分别为2.0909 ± 0.8312和3.1181 ± 0.8738。1年时（N = 9），4/9例受试者的下肢远端力量增加1个单位（平均值3.78（0.97）），8/9例受试者的下肢近端力量增加1个单位，平均值3.11（1.05）。对照组基线时下肢远端和近端的平均值分别为3.41（0.54）和3.0（1.0）。到1年时，3/5例受试者的下肢远端和近端力量降低1个单位（平均2.8（0.45）），5/5例受试者的下肢远端和近端力量降低1个单位，平均2.0（1.0）。与未治疗组相比，1年时髋屈肌、髋伸肌、髋外展肌和椎旁肌的肌肉功能也达到稳定。结论UC-MSCs移植不仅能稳定患者的肌力，而且对患者无GVHD或任何不良反应，因此与对照组相比，UC-MSCs治疗DMD是一种安全的选择，但还需要更大规模的双盲研究。
OBJECTIVE Duchenne muscular dystrophy (DMD) is a musculo-degenerative disease characterized by lack of dystrophin production with no definite cure available currently. Discarded umbilical cord is a potential source of mesenchymal stem cells which are non-immunogenic and can be used for transplantation in allogenic set ups. Given the regenerative and anti-inflammatory properties of mesenchymal stem cells (MSCs), here we investigated its role in the cellular therapy of DMD patients. DESIGN This is a single-blinded study conducted in various hospitals of India situated in Mumbai, Delhi, and Lucknow. Inclusion criteria for enrolling the patients in the study were boys aged between 5 to 18 years, absence of dystrophin in the immunohistochemistry of muscle biopsy and mutation in dystrophin gene in cytogenetic analysis. The exclusion criteria were presence of dystrophin in the muscle biopsy, patients on corticosteroids etc. UC-MSCs (2 millions/kg body weight) were administered through IV and IM injection. Muscle power in muscles of proximal upper limb, distal upper limb, proximal lower limb, distal lower limb, hip flexors, hip extensors, hip abductors, and paraspinal muscles were measured in 11 DMD patients after UC-MSCs transplantation and were followed for up to 3 years (average follow up 1.5 years). 5 DMD patients did not receive any UC-MSCs transplantation and served as the control group. RESULTS The treatment group (N = 11 at baseline) had a pretransplantation strength of 3.45 ± 1.0357 and 4.090 ± 0.8312 in muscles of proximal upper limb and distal upper limb respectively. After 1 year (N = 9) these strengths remained stable with an average of 3.78 (1.03) and 4.22 (0.83). In contrast, the control group (N = 5) has a pre-transplantation strength of 3.6 (0.54) and 4 (1) in the proximal and distal upper limb respectively. After 1 year, (N = 5) 3/5 subjects had a slight but not statistically significant decrease in the proximal upper limb, mean 3.0 (1.0) and 5/5 had a lunit decrease in strength, mean 3.0 (1.0). The treatment group had a pre-transplantation strength of 2.0909 ± 0.8312 and 3.1181 ± 0.8738 in muscles of distal and proximal lower limbs respectively. At 1 year (N = 9), 4/9 subjects had a 1 unit increase in strength in the distal lower limb (mean 3.78 (0.97)) and 8/9 subjects had a lunit increase in strength in the proximal lower limb, mean 3.11 (1.05). The control group has a mean of 3.41 (0.54) and 3.0 (1.0) at baseline in the distal and proximal lower limb respectively. By 1 year, 3/5 subjects had a 1 unit decrease (mean 2.8 (0.45)) and 5/5 had a lunit decrease, mean 2.0 (1.0) in distal and proximal lower limb strength. Stability in muscle function was also achieved in muscles of hip flexors, hip extensors, hip abductors, and paraspinal muscles at one year as compared to untreated group. CONCLUSION UC-MSCs administration not only resulted in the stabilization of muscle power but also did not show GVHD or any deleterious effects on the patients and thus may be considered as safe option for treatment of DMD as compared to control untreated group although further larger double-blinded studies are needed.