CD133+ cells isolated from various sources and their role in future clinical perspectives

Background. CD133 is a member of a novel family of cell surface glycoproteins. Initially, the expression of CD133 antigen was seen only in the hematopoietic derived CD34⁺ stem cells. At present, CD133 expression is demonstrated in undifferentiated epithelium, different types of tumors and myogenic cells. CD133⁺ neurosphere cells isolated from brain are able to differentiate into both neurons and glial cells. These data suggested that CD133 could be a specific marker for various stem and progenitor cell populations.

Objectives. The main goal would be to describe the role for CD133 as a marker of stem cells able to engraft and differentiate, to form functional non-hematopoietic adult lineages and contribute to disease amelioration via tissue regeneration.

Results/conclusion. In conclusion, since the rise of CD133 antigen as a suitable stem cell marker, the possible use of CD133⁺ stem cells in therapeutic applications has opened a new promising field in the treatment of degenerating diseases. The human circulating cells expressing the CD133 antigen behave as a stem cell population capable of commitment to hematopoietic, endothelial and myogenic lineages. CD133 cell therapy may represent a promising treatment for many diseases.     

Musculoskeletal simulation can help explain selective muscle degeneration in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disease that occurs due to the deficiency of the dystrophin protein. Although dystrophin is deficient in all muscles, it is unclear why degeneration progresses differently across muscles in DMD. We hypothesized that each muscle undergoes a different degree of eccentric contraction during gait, which could contribute to the selective degeneration in lower limb muscle, as indicated by various amounts of fatty infiltration. By comparing eccentric contractions quantified from a previous multibody dynamic musculoskeletal gait simulation and fat fractions quantified in a recent imaging study, our preliminary analyses show a strong correlation between eccentric contractions during gait and lower limb muscle fat fractions, supporting our hypothesis. This knowledge is critical for developing safe exercise regimens for the DMD population. This study also provides supportive evidence for using multiscale modeling and simulation of the musculoskeletal system in future DMD research. Muscle Nerve 52 : 174–182, 2015     

Lung function accurately predicts hypercapnia in patients with Duchenne muscular dystrophy

BACKGROUND: In patients with Duchenne muscular dystrophy (DMD), implementation of mechanical ventilation depends on sleep investigation and measurement of CO2 tension. The objective of this cross-sectional study was to determine which noninvasive lung function parameter best predicts nocturnal hypercapnia and diurnal hypercapnia in these patients. METHODS: According to transcutaneous CO2 (TcCO2) measurement, 114 DMD patients were classified into three groups: nocturnal hypercapnia (n = 38) [group N], diurnal hypercapnia (n = 39), despite nocturnal ventilation (group D), and 24-h normocapnia and spontaneous breathing (n = 37) [group S] as control. TcCO2 tension and lung function variables included vital capacity (VC) and maximal inspiratory pressure (MIP), and breathing pattern variables included tidal volume (Vt) and respiratory rate (RR), measured at the time of group inclusion. The rapid and shallow breathing index (RSBI [RR/Vt]) and Vt/VC ratio were calculated. Areas under the curve from the receiver operating characteristic (ROC) were calculated for those parameters. RESULTS: Compared to group S, lung function was significantly worse in group N and group D. VC, RR, and RSBI distinguished group S from group N by ROC comparison. Cut-off values of VC < or = 680 mL (ROC, 0.968), MIP < or = 22 cm H2O (ROC, 0.928), and Vt/VC > 0.33 (ROC, 0.923) accurately discriminated group D from group N, but RSBI, RR, and Vt did not. CONCLUSIONS: Lung function is useful to predict nocturnal hypercapnia in patients with DMD. Moreover, VC < 680 mL is very sensitive to predict daytime hypercapnia.     

自体分选干细胞治疗15例Duchenne型肌营养不良症的临床观察

目的 Duchenne型肌营养不良(Duchenne muscular dyswophy,DMD)是一种X链锁隐性遗传致死性肌病,抗肌萎缩蛋白(dystrophy)缺失如何引起肌肉变性、坏死具体机制不清,迄今尚无有效的治疗方法.该文试图探索应用自体分选干细胞治疗DMD的疗效.方法 从2008年9月至今该科收治15例DMD患者,男14例,女1例;年龄6～23岁;病程2～18年.13例DMD患者有不同程度"鸭步"行走,全身骨骼肌进行性无力,萎缩,腓肠肌纤维化致假性肥大,2例关节畸形挛缩.全部患者肌电图示肌源性损害,多项肌酶升高,尤以磷酸肌酸激酶(CK)显著,可高达10 600u/L,3例基因检测异常.自体干细胞采集15例中因4例体重不足20Kg者而直接采集骨髓;11例经G-CSF动员后COBE机采集外周血,CD_(34)~+干细胞经Clini MACS仪器分选,获得(1.0～5.6)×10~7的CD_(34)~+细胞,流式细胞仪检测阳性率80%.用分选CD_(34)~+细胞对患者做肌肉局部点状注射和细胞静脉回输;2个月后可再次治疗.结果 治疗后随诊1～5个月,13例患者行走有明显改善,腓肠肌纤维化程度减轻,局部变软,全身力量增加,关节肌肉训练度提高.2例挛缩肢体有松弛,疼痛有好转,在帮助下可以肢体活动.增高的多项肌酶下降,CK可下降1 000～5 000u/L不等.肌电图将在半年后复查.结论 应用自体分选干细胞为临床治疗DMD寻找到一条新途径,安全可行,其疗效可能与分选干细胞更利于提高调节自身免疫能力,使受损肌细胞再生修复有关.     

Alterations in mitochondrial function as a harbinger of cardiomyopathy: Lessons from the dystrophic heart

While compelling evidence supports the central role of mitochondrial dysfunction in the pathogenesis of heart failure, there is comparatively less information available on mitochondrial alterations that occur prior to failure. Building on our recent work with the dystrophin-deficient mdx mouse heart, this review focuses on how early changes in mitochondrial functional phenotype occur prior to overt cardiomyopathy and may be a determinant for the development of adverse cardiac remodelling leading to failure. These include alterations in energy substrate utilization and signalling of cell death through increased permeability of mitochondrial membranes, which may result from abnormal calcium handling, and production of reactive oxygen species. Furthermore, we will discuss evidence supporting the notion that these alterations in the dystrophin-deficient heart may represent an early “subclinical” signature of a defective nitric oxide/cGMP signalling pathway, as well as the potential benefit of mitochondria-targeted therapies. While the mdx mouse is an animal model of Duchenne muscular dystrophy (DMD), changes in the structural integrity of dystrophin, the mutated cytoskeletal protein responsible for DMD, have also recently been implicated as a common mechanism for contractile dysfunction in heart failure. In fact, altogether our findings support a critical role for dystrophin in maintaining optimal coupling between metabolism and contraction in the heart.