Abstract:
:In previous work, we engineered functional cell sheets using bone marrow-derived mesenchymal stem cells (BM-MSCs) to promote islet graft survival. In the present study, we hypothesized that a cell sheet using dermal fibroblasts could be an alternative to MSCs, and then we aimed to evaluate the effects of this cell sheet on the functional viability of human islets. Fibroblast sheets were fabricated using temperature-responsive culture dishes. Human islets were seeded onto fibroblast sheets. The efficacy of the fibroblast sheets was evaluated by dividing islets into three groups: the islets-alone group, the coculture with fibroblasts group, and the islet culture on fibroblast sheet group. The ultrastructure of the islets cultured on each fibroblast sheet was examined by electron microscopy. The fibroblast sheet expression of fibronectin (as a component of the extracellular matrix) was quantified by Western blotting. After 3 days of culture, islet viabilities were 70.2 ± 9.8%, 87.4 ± 5.8%, and 88.6 ± 4.5%, and survival rates were 60.3 ± 6.8%, 65.3 ± 3.0%, and 75.8 ± 5.6%, respectively. Insulin secretions in response to high-glucose stimulation were 5.1 ± 1.6, 9.4 ± 3.8, and 23.5 ± 12.4 µIU/islet, and interleukin-6 (IL-6) secretions were 3.0 ± 0.7, 5.1 ± 1.2, and 7.3 ± 1.0 ng/day, respectively. Islets were found to incorporate into the fibroblast sheets while maintaining a three-dimensional structure and well-preserved extracellular matrix. The fibroblast sheets exhibited a higher expression of fibronectin compared to fibroblasts alone. In conclusion, human dermal fibroblast sheets fabricated by tissue-engineering techniques could provide an optimal substrate for human islets, as a source of cytokines and extracellular matrix.
journal_name
Cell Transplantjournal_title
Cell transplantationauthors
Matsushima H,Kuroki T,Adachi T,Kitasato A,Ono S,Tanaka T,Hirabaru M,Kuroshima N,Hirayama T,Sakai Y,Soyama A,Hidaka M,Takatsuki M,Kin T,Shapiro J,Eguchi Sdoi
10.3727/096368916X690854subject
Has Abstractpub_date
2016-01-01 00:00:00pages
1525-37issue
8eissn
0963-6897issn
1555-3892pii
content-CT-1499_Matsushima_et_aljournal_volume
25pub_type
杂志文章abstract::Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent cells characterized by their self-renewal and differentiation potential. Accumulating clinical and preclinical evidence indicate MSCs are a promising cell source for regenerative medical therapies. However, undesirable immortalization, spontaneous trans...
journal_title:Cell transplantation
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journal_title:Cell transplantation
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章
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更新日期:2001-01-01 00:00:00
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journal_title:Cell transplantation
pub_type: 杂志文章
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journal_title:Cell transplantation
pub_type: 杂志文章,评审
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