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人胰岛在自组装肽水凝胶中的长期培养

Long-term cultures of human pancreatic islets in self-assembling peptides hydrogels.

作者信息

Marchini Amanda, Ciulla Maria Gessica, Antonioli Barbara, Agnoli Alessandro, Bovio Umberto, Visnoviz Virginia, Bertuzzi Federico, Gelain Fabrizio

机构信息

Institute for Stem-Cell Biology, Regenerative Medicine and Innovative Therapies (ISBReMIT), IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.

Center for Nanomedicine and Tissue Engineering (CNTE), ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.

出版信息

Front Bioeng Biotechnol. 2023 Feb 23;11:1105157. doi: 10.3389/fbioe.2023.1105157. eCollection 2023.

Abstract

Human pancreatic islets transplantation is an experimental therapeutic treatment for Type I Diabetes. Limited islets lifespan in culture remains the main drawback, due to the absence of native extracellular matrix as mechanical support after their enzymatic and mechanical isolation procedure. Extending the limited islets lifespan by creating a long-term culture remains a challenge. In this study, three biomimetic self-assembling peptides were proposed as potential candidates to recreate a pancreatic extracellular matrix, with the aim to mechanically and biologically support human pancreatic islets, by creating a three-dimensional culture system. The embedded human islets were analyzed for morphology and functionality in long-term cultures (14-and 28-days), by evaluating β-cells content, endocrine component, and extracellular matrix constituents. The three-dimensional support provided by HYDROSAP scaffold, and cultured into MIAMI medium, displayed a preserved islets functionality, a maintained rounded islets morphology and an invariable islets diameter up to 4 weeks, with results analogues to freshly-isolated islets. efficacy studies of the 3D cell culture system are ongoing; however, preliminary data suggest that human pancreatic islets pre-cultured for 2 weeks in HYDROSAP hydrogels and transplanted under subrenal capsule may restore normoglycemia in diabetic mice. Therefore, engineered self-assembling peptide scaffolds may provide a useful platform for long-term maintenance and preservation of functional human pancreatic islets .

摘要

人胰岛移植是治疗I型糖尿病的一种实验性治疗方法。由于在酶解和机械分离过程后缺乏天然细胞外基质作为机械支撑,培养中胰岛寿命有限仍然是主要缺点。通过建立长期培养来延长有限的胰岛寿命仍然是一个挑战。在本研究中,提出了三种仿生自组装肽作为重建胰腺细胞外基质的潜在候选物,目的是通过创建三维培养系统在机械和生物学方面支持人胰岛。通过评估β细胞含量、内分泌成分和细胞外基质成分,对长期培养(14天和28天)中包埋的人胰岛的形态和功能进行了分析。由HYDROSAP支架提供三维支撑并在MIAMI培养基中培养,显示出胰岛功能得以保留,胰岛形态保持圆形,胰岛直径在长达4周的时间内不变,结果与新鲜分离的胰岛相似。三维细胞培养系统的功效研究正在进行;然而,初步数据表明,在HYDROSAP水凝胶中预培养2周并移植到肾被膜下的人胰岛可能会使糖尿病小鼠恢复正常血糖。因此,工程化自组装肽支架可能为功能性人胰岛的长期维持和保存提供一个有用的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c4c/9995881/6d3d468b70a5/fbioe-11-1105157-g001.jpg

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