Introduction

Recellularization of organ decellularized extracellular matrix (dECM) offers a potential solution for organ shortage in allograft transplantation. Cell retention rates have ranged from 10 to 54% in varying approaches for reseeding cells in whole organ dECM scaffolds. We aimed to improve recellularization by using soluble gelatin as a cell carrier to deliver endothelial cells to the coronary vasculature and cardiomyocytes to the parenchyma in a whole decellularized rat heart.

Methods

Rat aortic endothelial cells (RAECs) were perfused over decellularized porcine aorta in low (1%) and high (5%) concentrations of gelatin to assess attachment to a vascular dECM model. After establishing cell viability and proliferation in 1% gelatin, we used 1% gelatin as a carrier to deliver RAECs and neonatal rat cardiomyocytes (NRCMs) to decellularized adult rat hearts. Immediate cell retention in the matrix was quantified, and recellularized hearts were evaluated for visible contractions up to 35 days after recellularization.

Results

We demonstrated that gelatin increased RAEC attachment to decellularized porcine aorta; blocking integrin receptors reversed this effect. In the whole rat heart gelatin (1%) increased retention of both RAECs and NRCMs respectively, compared with the control group (no gelatin). Gelatin was associated with visible contractions of NRCMs within hearts (87% with gelatin vs. 13% control).

Conclusions

Gelatin was an effective cell carrier for increasing cell retention and contraction in dECM. The gelatin-cell-ECM interactions likely mediated by integrin.

中文翻译：

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明胶促进脱细胞心脏细胞外基质血管和实质内的细胞保留

介绍

器官脱细胞细胞外基质 (dECM) 的再细胞化为同种异体移植中的器官短缺提供了潜在的解决方案。在整个器官 dECM 支架中重新接种细胞的不同方法中，细胞保留率从 10% 到 54% 不等。我们的目标是通过使用可溶性明胶作为细胞载体将内皮细胞递送至冠状血管系统并将心肌细胞递送至整个脱细胞大鼠心脏的实质，从而改善再细胞化。

方法

大鼠主动脉内皮细胞 (RAEC) 在低 (1%) 和高 (5%) 明胶浓度下灌注到去细胞猪主动脉上，以评估与血管 dECM 模型的附着情况。在 1% 明胶中建立细胞活力和增殖后，我们使用 1% 明胶作为载体将 RAEC 和新生大鼠心肌细胞 (NRCM) 输送到脱细胞的成年大鼠心脏。对基质中的立即细胞保留进行量化，并评估再细胞化心脏在再细胞化后长达 35 天的可见收缩。

结果

我们证明明胶增加了去细胞猪主动脉的 RAEC 附着；阻断整合素受体逆转了这种作用。与对照组（无明胶）相比，在整个大鼠心脏中，明胶（1%）分别增加了 RAEC 和 NRCM 的保留。明胶与心脏内 NRCM 的可见收缩有关（87% 的明胶与 13% 的对照）。

结论

明胶是一种有效的细胞载体，可增加 dECM 中的细胞保留和收缩。明胶-细胞-ECM 相互作用可能由整合素介导。