重组人胶原蛋白微球可减轻脂肪组织来源的基质细胞诱导的心脏传导减慢。
Recombinant human collagen-based microspheres mitigate cardiac conduction slowing induced by adipose tissue-derived stromal cells.
作者信息
Smit Nicoline W, Ten Sande Judith N, Parvizi Mojtaba, van Amersfoorth Shirley C M, Plantinga Josée A, van Spreuwel-Goossens Carolien A F M, van Dongen Elisabeth M W M, van Dessel Pascal F H M, Kluijtmans Sebastianus G J M, Meijborg Veronique M F, de Bakker Jacques M T, Harmsen Martin C, Coronel Ruben
机构信息
Heart Center, Department of Clinical and Experimental Cardiology, Academic Medical Center Amsterdam, University of Amsterdam, Amsterdam, Netherlands.
Netherlands Heart Institute, Holland Heart House, Utrecht, Netherlands.
出版信息
PLoS One. 2017 Aug 24;12(8):e0183481. doi: 10.1371/journal.pone.0183481. eCollection 2017.
BACKGROUND
Stem cell therapy to improve cardiac function after myocardial infarction is hampered by poor cell retention, while it may also increase the risk of arrhythmias by providing an arrhythmogenic substrate. We previously showed that porcine adipose tissue-derived-stromal cells (pASC) induce conduction slowing through paracrine actions, whereas rat ASC (rASC) and human ASC (hASC) induce conduction slowing by direct coupling. We postulate that biomaterial microspheres mitigate the conduction slowing influence of pASC by interacting with paracrine signaling.
AIM
To investigate the modulation of ASC-loaded recombinant human collagen-based microspheres, on the electrophysiological behavior of neonatal rat ventricular myocytes (NRVM).
METHOD
Unipolar extracellular electrograms, derived from microelectrode arrays (8x8 electrodes) containing NRVM, co-cultured with ASC or ASC loaded microspheres, were used to determine conduction velocity (CV) and conduction heterogeneity. Conditioned medium (Cme) of (co)cultures was used to assess paracrine mechanisms.
RESULTS
Microspheres did not affect CV in control (NRVM) monolayers. In co-cultures of NRVM and rASC, hASC or pASC, CV was lower than in controls (14.4±1.0, 13.0±0.6 and 9.0± 1.0 vs. 19.5±0.5 cm/s respectively, p<0.001). Microspheres loaded with either rASC or hASC still induced conduction slowing compared to controls (13.5±0.4 and 12.6±0.5 cm/s respectively, p<0.001). However, pASC loaded microspheres increased CV of NRVM compared to pASC and NRMV co-cultures (16.3±1.3 cm/s, p< 0.001) and did not differ from controls (p = NS). Cme of pASC reduced CV in control monolayers of NRVM (10.3±1.1 cm/s, p<0.001), similar to Cme derived from pASC-loaded microspheres (11.1±1.7 cm/s, p = 1.0). The presence of microspheres in monolayers of NRVM abolished the CV slowing influence of Cme pASC (15.9±1.0 cm/s, p = NS vs. control).
CONCLUSION
The application of recombinant human collagen-based microspheres mitigates indirect paracrine conduction slowing through interference with a secondary autocrine myocardial factor.
背景
心肌梗死后通过干细胞疗法改善心脏功能受到细胞留存率低的阻碍，同时干细胞疗法还可能通过提供致心律失常底物而增加心律失常风险。我们之前发现猪脂肪组织来源的基质细胞（pASC）通过旁分泌作用诱导传导减慢，而大鼠脂肪干细胞（rASC）和人脂肪干细胞（hASC）则通过直接耦联诱导传导减慢。我们推测生物材料微球通过与旁分泌信号相互作用减轻pASC对传导的减慢影响。
目的
研究负载脂肪干细胞的重组人胶原蛋白微球对新生大鼠心室肌细胞（NRVM）电生理行为的调节作用。
方法
使用包含NRVM的微电极阵列（8×8电极）记录的单极细胞外电图，这些NRVM与脂肪干细胞或负载脂肪干细胞的微球共培养，用于测定传导速度（CV）和传导异质性。（共）培养物的条件培养基（Cme）用于评估旁分泌机制。
结果
微球对对照（NRVM）单层细胞的CV没有影响。在NRVM与rASC、hASC或pASC的共培养中，CV低于对照组（分别为14.4±1.0、13.0±0.6和9.0±1.0 vs. 19.5±0.5 cm/s，p<0.001）。与对照组相比，负载rASC或hASC的微球仍可诱导传导减慢（分别为13.5±0.4和12.6±0.5 cm/s，p<0.001）。然而，与pASC和NRVM共培养相比，负载pASC的微球可增加NRVM的CV（16.3±1.3 cm/s，p<0.001），且与对照组无差异（p =无显著性差异）。pASC的Cme可降低NRVM对照单层细胞的CV（10.3±1.1 cm/s，p<0.001），与负载pASC的微球产生的Cme相似（11.1±1.7 cm/s, p = 1.0）。NRVM单层细胞中微球的存在消除了Cme pASC对CV的减慢影响（15.9±1.0 cm/s，与对照组相比p =无显著性差异）。
结论
应用重组人胶原蛋白微球通过干扰继发性自分泌心肌因子减轻间接旁分泌传导减慢。
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