Nunes Viviane A, Cavaçana Natale, Canovas Martha, Strauss Bryan E, Zatz Mayana
Human Genome Research Center, Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, SP, Brazil.
Biol Cell. 2007 Apr;99(4):185-96. doi: 10.1042/BC20060075.
Duchenne muscular dystrophy is a disease characterized by progressive and irreversible muscle degeneration for which there is no therapy. HUCB (human umbilical cord blood) has been considered as an important source of haematopoietic and mesenchymal stem cells, each having been shown to differentiate into distinct cell types. However, it remains unclear if these cells are able to differentiate into muscle cells.
We have showed that stem cells from HUCB did not differentiate into myotubes or express dystrophin when cultured in muscle-conditioned medium or with human muscle cells. However, delivery of GFP (green fluorescent protein)-transduced mononucleated cells from HUCB, which comprises both haematopoietic and mesenchymal populations, into quadriceps muscle of mdx (mouse dystrophy X-chromosome linked) mice resulted in the expression of human myogenic markers. After recovery of these cells from mdx muscle and in vitro cultivation, they were able to fuse and form GFP-positive myotubes that expressed dystrophin.
These results indicate that chemical factors and cell-to-cell contact provided by in vitro conditions were not enough to trigger the differentiation of stem cells into muscle cells. Nevertheless, we showed that the HUCB-derived stem cells were capable of acquiring a muscle phenotype after exposure to an in vivo muscle environment, which was required to activate the differentiation programme.
杜兴氏肌营养不良症是一种以进行性和不可逆性肌肉退化为特征的疾病,目前尚无治疗方法。人脐带血(HUCB)被认为是造血干细胞和间充质干细胞的重要来源,研究表明这两种干细胞均可分化为不同的细胞类型。然而,这些细胞是否能够分化为肌肉细胞仍不清楚。
我们发现,当在肌肉条件培养基中培养或与人类肌肉细胞共同培养时,来自人脐带血的干细胞不会分化为肌管或表达抗肌萎缩蛋白。然而,将转导了绿色荧光蛋白(GFP)的人脐带血单核细胞(其中包含造血细胞和间充质细胞群体)注入mdx(X染色体连锁的小鼠肌营养不良症)小鼠的股四头肌后,会导致人类肌源性标志物的表达。从mdx小鼠肌肉中回收这些细胞并进行体外培养后,它们能够融合并形成表达抗肌萎缩蛋白的GFP阳性肌管。
这些结果表明,体外条件提供的化学因子和细胞间接触不足以触发干细胞分化为肌肉细胞。尽管如此,我们表明,人脐带血来源的干细胞在暴露于体内肌肉环境后能够获得肌肉表型,而这是激活分化程序所必需的。