Bromodeoxyuridine increases multipotency of human bone marrow-derived stem cells.
Bromodeoxyuridine increases multipotency of human bone marrow-derived stem cells.
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发表时间：
2004
影响因子：
2.8
通讯作者：
T. Qu;X. Dong;I. Sugaya;A. Vaghani;J. Pulido;K. Sugaya
中科院分区：
文献类型：
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作者：
T. Qu;X. Dong;I. Sugaya;A. Vaghani;J. Pulido;K. Sugaya
目的最近的报告表明，骨髓间充质干细胞（MeSC）可能具有分化成与其表型胚胎起源无关的多种细胞类型的能力，包括神经细胞。虽然在“体外”和新生儿身上得到了证明，但在成年动物大脑中证明这种能力的努力却取得了有限的成功。如果能够证明人类 MeSC (HMeSC) 可以分化为成人大脑中的神经细胞，那么 HMeSC 在神经系统疾病的细胞替代疗法中可能具有潜在的治疗用途。在这里，我们证明，当在体外和成年动物中提供适当的谱系特异性分化信号时，用 5-bromo-2-deoxyuridine (BrdU) 处理 3 周的成年 HMeSC 具有分化为神经细胞和视网膜细胞的能力。未经BrdU处理的HMeSC在体外或成年动物中不能分化为神经元或成年动物中的视网膜细胞。方法 用 BrdU (3 muM) 处理从成人骨髓中分离的 MeSCs 3 周，然后进行体外和体内分化条件。结果 BrdU 预处理的 HMeSC 在与分化的人神经干细胞共培养后以及移植到成年大鼠脑中后表达神经元和神经胶质标记。用 BrdU 和转化生长因子-β3 预处理的 HMeSC 在移植到成年大鼠玻璃体后表达光感受器标记。结论 这些结果表明，BrdU 治疗可能会增加 HMeSC 的多能性，有可能用于神经和眼科疾病的自体细胞疗法。
PURPOSE Recent reports show that marrow derived mesenchymal stem cells (MeSCs) may have the ability to differentiate into diverse cell types unrelated to their phenotypical embryonic origin, including neural cells. While demonstrated "in vitro" and neonatally, efforts to demonstrate this ability in adult animal brains have had limited success. If it can be shown that human MeSC (HMeSC) can differentiate into neural cells in adult brain, it would open up the possibility that HMeSCs may be of potential therapeutic use in cell replacement therapies for neurological diseases. Here, we demonstrate that adult HMeSCs treated with 5-bromo-2-deoxyuridine (BrdU) for 3 weeks develop the capability to differentiate into neural and retinal cells when provided the appropriate lineage specific differentiation signals in vitro and in adult animals. HMeSC without BrdU treatment did not differentiate into neurons in vitro or adult animal or retinal cells in adult animal. METHODS MeSCs isolated from adult human bone marrow were treated with BrdU (3 muM) for 3 weeks and then subjected to differentiation conditions both in vitro and in vivo. RESULTS BrdU pretreated HMeSCs express neuronal and glial markers after co-culture with differentiated human neural stem cells and after transplantation into the adult rat brain. HMeSCs pretreated with BrdU and transforming growth factor-beta3 express a photoreceptor marker after transplantation into the adult rat vitreous. CONCLUSIONS These results suggest that BrdU treatment may increase the multipotency of HMeSCs for possible use in autologous cell therapies for neurological and opthamological diseases.