Partially Digested Adult Cardiac Extracellular Matrix Promotes Cardiomyocyte Proliferation In Vitro.
Partially Digested Adult Cardiac Extracellular Matrix Promotes Cardiomyocyte Proliferation In Vitro.
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部分消化的成人心脏细胞外基质促进体外心肌细胞增殖。
DOI：
10.1002/adhm.201500035
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发表时间：
2015
影响因子：
10
通讯作者：
Black3rd,LaurenD
中科院分区：
文献类型：
--
作者：
Williams,Corin;Sullivan,Kelly;Black3rd,LaurenD
刺激或维持出生后哺乳动物心肌细胞的增殖能力是心脏再生的主要挑战。早期研究发现，胎儿心肌细胞外基质（ECM）比新生或成人ECM更能促进体外培养的乳鼠心肌细胞增殖。假设成人ECM（PD-ECM）的部分消化将释放促进心肌细胞增殖的较少交联的组分，类似于胎儿ECM。将新生大鼠心脏细胞接种到包被有成年大鼠心脏ECM的基质上，该基质已在胃蛋白酶-HCl中溶解1、3、6、12、24或48 h。与其他条件相比，1至5天的心肌细胞增殖和数量变化倍数在1和3 h PD-ECM上最高。肌节倾向于在24和48小时PD-ECM上成熟，其中观察到低增殖。3 h PD-ECM主要由原纤维蛋白-1、纤维蛋白原和层粘连蛋白组成，而48 h PD-ECM主要由胶原蛋白I组成。我们的研究结果表明，成人ECM保留再生线索，可能被更丰富，成熟的ECM成分掩盖。PD-ECM提供了一种简单而强大的促进心肌细胞增殖的方法。
Stimulating or maintaining the proliferative capacity of postnatal mammalian cardiomyocytes is a major challenge to cardiac regeneration. Previously, it is found that fetal cardiac extracellular matrix (ECM) can promote neonatal rat cardiomyocyte proliferation in vitro better than neonatal or adult ECM. It is hypothesized that partial digestion of adult ECM (PD‐ECM) would liberate less crosslinked components that promote cardiomyocyte proliferation, similar to fetal ECM. Neonatal rat cardiac cells are seeded onto substrates coated with adult rat cardiac ECM that has been solubilized in pepsin‐HCl for 1, 3, 6, 12, 24, or 48 h. Cardiomyocyte proliferation and fold‐change in numbers from 1 to 5 d are highest on 1 and 3 h PD‐ECM compared to other conditions. Sarcomeres tend to mature on 24 and 48 h PD‐ECM where low proliferation is observed. 3 h PD‐ECM is primarily composed of Fibrillin‐1, Fibrinogen, and Laminins while 48 h PD‐ECM is dominated by Collagen I. Our results suggest that adult ECM retains regenerative cues that may be masked by more abundant, mature ECM components. PD‐ECM provides a simple yet powerful approach to promoting cardiomyocyte proliferation.