Reaching out: junctions between cardiac telocytes and cardiac stem cells in culture.

Reaching out: junctions between cardiac telocytes and cardiac stem cells in culture.
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DOI:
10.1111/jcmm.12719
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发表时间:
2016-02
影响因子:
5.3
通讯作者:
Gherghiceanu M
Gherghiceanu M
中科院分区:
医学2区
文献类型:
--
作者:
Popescu LM;Fertig ET;Gherghiceanu M

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我们的研究小组先前发现,在心脏干细胞(CSC)中,远端细胞(tc)与干细胞/祖细胞形成串联,在心脏更新中发挥各种作用。其中,通过直接物理接触(连接)以及远距离、旁分泌信号或通过含有mRNA的细胞外囊泡“护理”CSCs的能力。我们使用电子显微镜在心脏tc和CSCs共培养中识别连接(如间隙或粘附连接)。在tc之间观察到间隙连接,形成网络,但在tc和csc之间没有观察到间隙连接。相反,我们发现TCs和CSCs在培养中相互作用,形成异细胞粘附连接,以及非经典连接,如粘附点和基质突触。在TCs和CSCs(两种基质细胞)之间形成的基质突触通常与连接两个对立膜的电子致密纳米结构(平均长度约为15 nm)的存在有关。突触间隙的平均宽度为30 nm,细胞间接触的平均长度为5 μm。最近的研究表明,干细胞不能在受损心肌的恶劣环境中充分植入和存活,可能是由于缺乏促再生成分的分泌组(旁分泌因子)和/或邻近的支持细胞。在此,我们强调共培养中描述的连接与原位tc和CSCs之间确定的连接之间的相似性。在培养中复制CSC生态位可能是单细胞治疗的可行替代方案。
Telocytes (TCs) were previously shown by our group to form a tandem with stem/progenitor cells in cardiac stem cell (CSC) niches, fulfilling various roles in cardiac renewal. Among these, the ability to ‘nurse’ CSCs in situ, both through direct physical contact (junctions) as well as at a distance, by paracrine signalling or through extracellular vesicles containing mRNA. We employed electron microscopy to identify junctions (such as gap or adherens junctions) in a co‐culture of cardiac TCs and CSCs. Gap junctions were observed between TCs, which formed networks, however, not between TCs and CSCs. Instead, we show that TCs and CSCs interact in culture forming heterocellular adherens junctions, as well as non‐classical junctions such as puncta adherentia and stromal synapses. The stromal synapse formed between TCs and CSCs (both stromal cells) was frequently associated with the presence of electron‐dense nanostructures (on average about 15 nm in length) connecting the two opposing membranes. The average width of the synaptic cleft was 30 nm, whereas the average length of the intercellular contact was 5 μm. Recent studies have shown that stem cells fail to adequately engraft and survive in the hostile environment of the injured myocardium, possibly as a result of the absence of the pro‐regenerative components of the secretome (paracrine factors) and/or of neighbouring support cells. Herein, we emphasize the similarities between the junctions described in co‐culture and the junctions identified between TCs and CSCs in situ. Reproducing a CSC niche in culture may represent a viable alternative to mono‐cellular therapies.