Conversion from human haematopoietic stem cells to keratinocytes requires keratinocyte secretory factors

Conversion from human haematopoietic stem cells to keratinocytes requires keratinocyte secretory factors
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人类造血干细胞向角质形成细胞的转化需要角质形成细胞分泌因子

DOI:
10.1111/j.1365-2230.2011.04312.x
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发表时间:
2012
影响因子:
4.1
通讯作者:
et al.
et al.
中科院分区:
医学4区
文献类型:
--
作者:
Fujita Y;Inokuma D;et al.

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背景:最近的研究报道,骨髓源性干细胞(BMSCs),包括造血干细胞(HSC)和间充质基质细胞(Mesenchymal stromal cells),可分化为多种细胞谱系。基于这些发现,已知BMSCs可用于临床治疗各种疾病,如心肌梗死和神经创伤性损伤。然而,HSC转化为器官细胞的机制尚不完全清楚。该机制被怀疑涉及BMSC、受损器官细胞和来自器官的旁分泌调节的可溶性因子之间的直接细胞-细胞相互作用,但迄今为止,目的:探讨HSC体外分化为角朊细胞的机制和必要条件。结果:hHSCs与小鼠角质形成细胞共培养诱导人角蛋白14和转氨酶I的表达。只有0.1%的分化角质形成细胞具有多个细胞核,表明细胞融合。hHSC与固定的鼠角质形成细胞(预测稳定细胞组分)的共培养未能诱导转化为角质形成细胞。相反,从人类和小鼠角质形成细胞的角质形成细胞条件培养基被发现介导hHSC转化为keratinocytes.Conclusions。人类HSC能够分化为角质形成细胞,细胞融合是非常罕见的。这种分化是由血浆环境介导的,而不是直接的细胞-细胞相互作用。
Background.Recent studies have reported that bone‐marrow‐derived stem cells (BMSCs), including haematopoietic stem cells (HSCs) and mesenchymal stromal cells, differentiate in order to regenerate various cellular lineages. Based on these findings, it is known that BMSCs can be used clinically to treat various disorders, such as myocardial infarction and neurotraumatic injuries. However, the mechanism of HSC conversion into organ cells is incompletely understood. The mechanism is suspected to involve direct cell–cell interaction between BMSCs, damaged organ cells, and paracrine‐regulated soluble factors from the organ, but to date, there have been no investigations into which of these are essential for keratinocyte differentiation from HSCs.Aim.To elucidate the mechanism and necessary conditions for HSC differentiation into keratinocytesin vitro.Methods.We cultured human (h)HSCs under various conditions to try to elucidate the mechanism and necessary conditions for hHSCs to differentiate into keratinocytes.Result.hHSCs cocultured with mouse keratinocytes induced expression of human keratin 14 and transglutaminase I. Only 0.1% of the differentiated keratinocytes possessed multiple nuclei indicating cell fusion. Coculture of hHSCs with fixed murine keratinocytes (predicted to stabilize cellular components) failed to induce conversion into keratinocytes. Conversely, keratinocyte‐conditioned medium from both human and mouse keratinocytes was found to mediate hHSC conversion into keratinocytes.Conclusions.Human HSCs are capable of differentiation into keratinocytes, and cell fusion is extremely rare. This differentiating is mediated by the plasma environment rather than by direct cell–cell interactions.
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