A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation.
A gelatin hydrogel nonwoven fabric improves outcomes of subcutaneous islet transplantation.
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DOI：
10.1038/s41598-023-39212-4
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发表时间：
2023-07-24
影响因子：
4.6
通讯作者：
Goto, Masafumi
中科院分区：
文献类型：
--
作者：
Kanai, Norifumi;Inagaki, Akiko;Nakamura, Yasuhiro;Imura, Takehiro;Mitsugashira, Hiroaki;Saito, Ryusuke;Miyagi, Shigehito;Watanabe, Kimiko;Kamei, Takashi;Unno, Michiaki;Tabata, Yasuhiko;Goto, Masafumi
皮下胰岛移植是治疗严重糖尿病的一种很有前途的方法，然而，移植不良阻碍了它的流行。我们以前报道过，重组肽（RCP）增强皮下胰岛移植。然而，它是不切实际的临床应用，因为RCP必须删除移植胰岛时。我们在此研究了一种新的生物可吸收明胶水凝胶非织造织物（GHNF）是否可以改善皮下胰岛移植。将具有或不具有GHNF的硅垫片植入糖尿病小鼠的皮下空间中。将同系胰岛移植到预处理的间隙或门静脉内（Ipo组）。检测血糖、腹腔葡萄糖耐量、免疫组化、CT血管造影及基因表达。GHNF组的治愈率和糖耐量明显优于对照组和Ipo组（分别为P < 0.01和P < 0.05）。在GHNF组中，在胰岛囊中检测到vWF阳性血管的有限增加，而层粘连蛋白（p < 0.05）、胶原III和IV显著增强。TaqMan阵列显示，在预处理的空间中，19个靶基因（包括胰岛素样生长因子-2）显著上调。GHNF显著改善了皮下胰岛移植的结果，可能是由于ECM补偿和各种生长因子对胰岛功能的保护，而不是增强新生血管形成。
Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously reported that a recombinant peptide (RCP) enhances subcutaneous islet engraftment. However, it is impractical for clinical use because RCP must be removed when transplanting islets. We herein investigated whether a novel bioabsorbable gelatin hydrogel nonwoven fabric (GHNF) could improve subcutaneous islet engraftment. A silicon spacer with or without GHNF was implanted into the subcutaneous space of diabetic mice. Syngeneic islets were transplanted into the pretreated space or intraportally (Ipo group). Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, CT angiography and gene expression were evaluated. The cure rate and glucose tolerance of the GHNF group were significantly better than in the control and Ipo groups (p < 0.01, p < 0.05, respectively). In the GHNF group, a limited increase of vWF-positive vessels was detected in the islet capsule, whereas laminin (p < 0.05), collagen III and IV were considerably enhanced. TaqMan arrays revealed a significant upregulation of 19 target genes (including insulin-like growth factor-2) in the pretreated space. GHNF markedly improved the subcutaneous islet transplantation outcomes, likely due to ECM compensation and protection of islet function by various growth factors, rather than enhanced neovascularization.
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