Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle.

Transplanted hematopoietic stem cells demonstrate impaired sarcoglycan expression after engraftment into cardiac and skeletal muscle.
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移植的造血干细胞在植入心肌和骨骼肌后表现出肌聚糖表达受损。

DOI:
10.1172/jci23071
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发表时间:
2004
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
E. McNally
E. McNally
中科院分区:
--
文献类型:
--
作者:
K. Lapidos;Y. Chen;Judy U Earley;A. Heydemann;Jill M. Huber;Marcia Chien;A. Ma;E. McNally

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多能骨髓衍生侧群 (BM-SP) 干细胞已被证明可以重新填充造血系统,并有助于移植后骨骼和心肌的再生。我们使用缺乏 δ-肌聚糖的心肌病和肌营养不良症模型测试了 BM-SP 细胞再生心脏和骨骼肌的能力。缺乏δ-肌聚糖会在心脏和骨骼肌中产生微梗塞,从而招募再生干细胞。此外,移植后肌聚糖的表达应标志着干细胞成功成熟为心肌和骨骼肌谱系。将来自正常雄性小鼠的 BM-SP 细胞移植到 δ-肌聚糖缺失的雌性小鼠中。我们检测到供体来源的干细胞植入骨骼肌中,其中大多数供体来源的细胞并入肌纤维内。在心脏中,在心肌细胞内检测到来自供体的细胞核。含有供体来源的细胞核的骨骼肌肌纤维通常无法表达肌聚糖,在分析的所有 14 只小鼠的股四头肌中仅检测到 2 条肌聚糖阳性纤维。此外,所有具有供体来源的细胞核的心肌细胞均为肌聚糖阴性。移植后心肌细胞和骨骼肌纤维中肌聚糖表达的缺失表明骨髓干细胞的分化和/或成熟受损。 BM-SP 细胞无法表达这种蛋白质,严重限制了它们在心肌和骨骼肌再生中的效用。
Pluripotent bone marrow-derived side population (BM-SP) stem cells have been shown to repopulate the hematopoietic system and to contribute to skeletal and cardiac muscle regeneration after transplantation. We tested BM-SP cells for their ability to regenerate heart and skeletal muscle using a model of cardiomyopathy and muscular dystrophy that lacks delta-sarcoglycan. The absence of delta-sarcoglycan produces microinfarcts in heart and skeletal muscle that should recruit regenerative stem cells. Additionally, sarcoglycan expression after transplantation should mark successful stem cell maturation into cardiac and skeletal muscle lineages. BM-SP cells from normal male mice were transplanted into female delta-sarcoglycan-null mice. We detected engraftment of donor-derived stem cells into skeletal muscle, with the majority of donor-derived cells incorporated within myofibers. In the heart, donor-derived nuclei were detected inside cardiomyocytes. Skeletal muscle myofibers containing donor-derived nuclei generally failed to express sarcoglycan, with only 2 sarcoglycan-positive fibers detected in the quadriceps muscle from all 14 mice analyzed. Moreover, all cardiomyocytes with donor-derived nuclei were sarcoglycan-negative. The absence of sarcoglycan expression in cardiomyocytes and skeletal myofibers after transplantation indicates impaired differentiation and/or maturation of bone marrow-derived stem cells. The inability of BM-SP cells to express this protein severely limits their utility for cardiac and skeletal muscle regeneration.
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发表时间: 2002-02-01
影响因子: 3.5
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