Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: In vitro and in vivo studies
Pancreatic acellular matrix supports islet survival and function in a synthetic tubular device: In vitro and in vivo studies
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DOI：
10.3892/ijmm_00000330
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
Parnigotto, P. P.
中科院分区：
文献类型：
--
作者：
De Carlo, E.;Baiguera, S.;Parnigotto, P. P.
提高胰岛的存活率和功能是获得治疗1型糖尿病的有价值的生物人工胰腺的起点。在这种情况下，在去除组织细胞桶后获得的脱细胞基质，已知可以支持几种细胞类型的体外粘附、生长和功能。我们证明了一个同源的无细胞胰腺基质是一个合适的支架大鼠胰岛培养维持其长期活力和功能。在长期体外培养过程中，粘附于胰腺基质的胰岛表现出持续的葡萄糖诱导的胰岛素释放，而无基质或肝基质培养的胰岛则表现出逐渐减少。为了获得可植入的装置，将脱细胞基质/胰岛培养物包埋在通过冷冻/解冻程序获得的聚乙烯醇(PVA)/聚乙二醇（PEG）管中。在此条件下，检测到体外胰岛素恒定释放。然后将该装置植入糖尿病大鼠体内，发现该装置中含有的胰岛胰岛素分泌活性降低了胰岛素需求。的确，免疫荧光证实了产生胰岛素和胰高血糖素的细胞存在于移植的装置中。这些数据表明，PVA/PEG半透膜可以获得至少部分恢复胰岛素分泌的装置。
Increasing pancreatic islet survival and function is a starting point for obtaining a valuable bioartificial pancreas for the treatment of type I diabetes. In this context, decellularized matrices, obtained after the removal of tissue cellular pail, are known to support in vitro adhesion, growth, and function of several cell types. We demonstrate that a homologous acellular pancreatic matrix is a suitable scaffold for rat islet cultures maintaining their long-term viability and function. Islets adhered to the pancreatic matrix showed a constant glucose-induced insulin release during long-term in vitro incubation, while islets cultured without a matrix or on the liver matrix showed a progressive reduction. In order to obtain implantable devices, acellular matrix/islet cultures were entrapped into poly(vinyl alcohol) (PVA)/poly(ethylene glycol) (PEG) tubes obtained by the freezing/thawing procedure. Under this condition, an in vitro constant insulin release was detected. The devices were then implanted into diabetic rats where reduced insulin requirement was noted suggesting insulin secretory activity of islets contained in the device. Indeed, immunofluorescence confirmed the presence of insulin- and glucagon-producing cells into the explanted devices. These data show that PVA/PEG semi-permeable membrane can obtain devices that restore, at least in part, insulin secretion.