Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice.
Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice.
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DOI：
10.1038/s41536-022-00249-0
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发表时间：
2022-09-02
影响因子：
7.2
通讯作者：
Perlingeiro, Rita C. R.
中科院分区：
文献类型：
--
作者：
Azzag, Karim;Bosnakovski, Darko;Tungtur, Sudheer;Salama, Peter;Kyba, Michael;Perlingeiro, Rita C. R.
面肩肱型肌营养不良症（FSHD）是由DUX 4基因的不适当沉默引起的遗传显性进行性肌病，导致纤维化、肌肉萎缩和脂肪替代。专注于通过干细胞递送的肌肉再生的方法代表了肌营养不良症的有吸引力的治疗选择。为了研究FSHD中细胞移植的潜力，我们使用了多西环素调节的iDUX 4pA-HSA小鼠模型，其中可以在骨骼肌中诱导低水平DUX 4。我们发现，小鼠多能干细胞（PSC）衍生的肌源性祖细胞移植在肌肉积极进行DUX 4介导的变性。供体来源的肌肉组织显示出减少的纤维化，重要的是，与非移植对照相比，移植的肌肉显示出改善的收缩比力。这些数据证明了在FSHD小鼠模型中用PSC衍生的肌源性祖细胞替代患病肌肉的可行性，并突出了这种细胞治疗方法的临床益处的潜力。
Facioscapulohumeral muscular dystrophy (FSHD) is a genetically dominant progressive myopathy caused by improper silencing of the DUX4 gene, leading to fibrosis, muscle atrophy, and fatty replacement. Approaches focused on muscle regeneration through the delivery of stem cells represent an attractive therapeutic option for muscular dystrophies. To investigate the potential for cell transplantation in FSHD, we have used the doxycycline-regulated iDUX4pA-HSA mouse model in which low-level DUX4 can be induced in skeletal muscle. We find that mouse pluripotent stem cell (PSC)-derived myogenic progenitors engraft in muscle actively undergoing DUX4-mediated degeneration. Donor-derived muscle tissue displayed reduced fibrosis and importantly, engrafted muscles showed improved contractile specific force compared to non-transplanted controls. These data demonstrate the feasibility of replacement of diseased muscle with PSC-derived myogenic progenitors in a mouse model for FSHD, and highlight the potential for the clinical benefit of such a cell therapy approach.
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影响因子：
16.6
作者：
通讯作者：
--
DOI：
10.1038/mt.2016.111
发表时间：
2016-08
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
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通讯作者：
TREMBLAY, JP
影响因子：
64.8
作者：
Gabellini, D;D'Antona, G;Tupler, R
通讯作者：
Tupler, R
影响因子：
4.9
作者：
Arpke RW;Shams AS;Collins BC;Larson AA;Lu N;Lowe DA;Kyba M
通讯作者：
Kyba M