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通过用胰岛细胞再种植去细胞化的大鼠胰腺来构建内分泌的新型胰腺。

Engineering an endocrine Neo-Pancreas by repopulation of a decellularized rat pancreas with islets of Langerhans.

机构信息

Department of Surgery, Campus Charité Mitte and Campus Virchow Klinikum, Charité - Universitätsmedizin Berlin, Germany.

Department of Radiolgoy, Charité - Universitätsmedizin Berlin, Germany.

出版信息

Sci Rep. 2017 Feb 2;7:41777. doi: 10.1038/srep41777.

DOI:10.1038/srep41777
PMID:28150744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5288794/
Abstract

Decellularization of pancreata and repopulation of these non-immunogenic matrices with islets and endothelial cells could provide transplantable, endocrine Neo- Pancreata. In this study, rat pancreata were perfusion decellularized and repopulated with intact islets, comparing three perfusion routes (Artery, Portal Vein, Pancreatic Duct). Decellularization effectively removed all cellular components but conserved the pancreas specific extracellular matrix. Digital subtraction angiography of the matrices showed a conserved integrity of the decellularized vascular system but a contrast emersion into the parenchyma via the decellularized pancreatic duct. Islets infused via the pancreatic duct leaked from the ductular system into the peri-ductular decellularized space despite their magnitude. TUNEL staining and Glucose stimulated insulin secretion revealed that islets were viable and functional after the process. We present the first available protocol for perfusion decellularization of rat pancreata via three different perfusion routes. Furthermore, we provide first proof-of-concept for the repopulation of the decellularized rat pancreata with functional islets of Langerhans. The presented technique can serve as a bioengineering platform to generate implantable and functional endocrine Neo-Pancreata.

摘要

通过对这些非免疫原性基质进行脱细胞处理并重新填充胰岛和内皮细胞，可以提供可移植的内分泌性 Neo-Pancreata。在这项研究中，我们使用完整的胰岛对大鼠胰腺进行了灌注脱细胞处理并重新填充，比较了三种灌注途径（动脉、门静脉、胰腺导管）。脱细胞处理有效地去除了所有的细胞成分，但保留了胰腺特有的细胞外基质。基质的数字减影血管造影显示，脱细胞处理的血管系统保持完整，但通过脱细胞处理的胰腺导管将造影剂渗出到实质中。尽管胰岛的数量很大，但通过胰腺导管输注的胰岛会从导管系统漏入导管周围的脱细胞空间。TUNEL 染色和葡萄糖刺激胰岛素分泌显示，胰岛在处理后仍然具有活力和功能。我们提出了一种通过三种不同灌注途径对大鼠胰腺进行灌注脱细胞处理的可行方案。此外，我们首次证明了可以用功能性胰岛对脱细胞处理的大鼠胰腺进行重新填充。所提出的技术可以作为一种生物工程平台，用于生成可植入的功能性内分泌性 Neo-Pancreata。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/b50c933a3511/srep41777-f8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/6c9452d9a5f3/srep41777-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/138f3a0ab4e0/srep41777-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/b50c933a3511/srep41777-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/16b2c0d97922/srep41777-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/7289fda19f79/srep41777-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/b6646181082a/srep41777-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/07a82b3e4cfe/srep41777-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/6d27f4371fc0/srep41777-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/6c9452d9a5f3/srep41777-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/138f3a0ab4e0/srep41777-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ddd/5288794/b50c933a3511/srep41777-f8.jpg

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