Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas.
Extracellular matrix scaffold and hydrogel derived from decellularized and delipidized human pancreas.
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DOI：
10.1038/s41598-018-28857-1
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发表时间：
2018-07-11
影响因子：
4.6
通讯作者：
Odorico JS
中科院分区：
文献类型：
--
作者：
Sackett SD;Tremmel DM;Ma F;Feeney AK;Maguire RM;Brown ME;Zhou Y;Li X;O'Brien C;Li L;Burlingham WJ;Odorico JS
细胞外基质（ECM）通过结构和生化刺激调节细胞行为，在发育中起着重要的作用。通过脱细胞化获得的组织特异性ECM已经在用于组织和器官替代的几种策略中提出。已有动物胰腺脱细胞的报道，但由于脂质含量较高，应用于人类胰腺的相同方法效果较差。此外，ECM衍生的水凝胶可以从许多脱细胞组织中获得，但尚未报道获得人胰腺衍生的水凝胶的方法。使用新的人胰腺脱细胞方法，我们生产了一种适合组织培养、移植和蛋白质组学应用的无细胞三维生物支架（hP-ECM）和水凝胶（hP-HG）。在去细胞化方案中包括均质化步骤显著改善了所得ECM的脂质去除和凝胶化能力，其能够在体外和体内在37 °C下凝胶化，并且在体外与多种细胞类型和胰岛样组织细胞相容。总体而言，本研究证明了用于人胰腺组织的脱细胞化和去脂化的新方案的表征，该新方案用于生产适用于细胞培养和移植应用的脱细胞ECM和ECM水凝胶。我们还报告了人类胰腺基质体内存在的120种蛋白质。
Extracellular matrix (ECM) plays an important developmental role by regulating cell behaviour through structural and biochemical stimulation. Tissue-specific ECM, attained through decellularization, has been proposed in several strategies for tissue and organ replacement. Decellularization of animal pancreata has been reported, but the same methods applied to human pancreas are less effective due to higher lipid content. Moreover, ECM-derived hydrogels can be obtained from many decellularized tissues, but methods have not been reported to obtain human pancreas-derived hydrogel. Using novel decellularization methods with human pancreas we produced an acellular, 3D biological scaffold (hP-ECM) and hydrogel (hP-HG) amenable to tissue culture, transplantation and proteomic applications. The inclusion of a homogenization step in the decellularization protocol significantly improved lipid removal and gelation capability of the resulting ECM, which was capable of gelation at 37 °C in vitro and in vivo, and is cytocompatible with a variety of cell types and islet-like tissues in vitro. Overall, this study demonstrates the characterisation of a novel protocol for the decellularization and delipidization of human pancreatic tissue for the production of acellular ECM and ECM hydrogel suitable for cell culture and transplantation applications. We also report a list of 120 proteins present within the human pancreatic matrisome.