Expression of Transforming Growth Factor-β by Human Islets: Impact on Islet Viability and Function

Sabek, Omaima; Fraga, Daniel; Henry, James; Gaber, Lillian W.; Kotb, Malak; Gaber, A. Osama

doi:10.3727/000000007783465217

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…The present findings demonstrated elevated secretions of TGF-β and IL-6 in islets cocultured with fibroblasts. The role of TGF-β in the production of ECM has been revealed, and TGF-β1 gene therapy has been shown to have a protective effect on islet survival 36–38 .…”

Section: Discussionmentioning

confidence: 99%

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function in Vitro

et al. 2016

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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.

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Section: Discussionmentioning

confidence: 99%

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function in Vitro

et al. 2016

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“…The unlimited in vitro proliferative capacity of TSCs (or of ESCs used to produce trophoblast cells) not only ensures unlimited supply, but also significantly facilitates genetic manipulation, thus providing a convenient starting point for developing off-the-shelf cytokine delivery systems. By contrast, genetic manipulation of primary cells—usually by viral transduction (6, 26)—must be done repeatedly, is less reproducible, and attempts to increase transduction efficiency tend to reduce viability (6). The long, but not indefinite, duration of intrahepatic TSC survival (which exceeds normal trophoblast life span more than threefold) makes these cells particularly interesting as conditioning reagents, especially because the hepatic environment is known to facilitate tolerance induction (3).…”

Section: Discussionmentioning

confidence: 99%

Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

et al. 2009

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In view of the well-known phenomenon of trophoblast immune privilege, trophoblast stem cells (TSCs) might be expected to be immune privileged, which could be of interest for cell or gene therapies. Yet in the ectopic sites tested so far, TSC transplants fail to show noticeable immune privilege and seem to lack physiological support. However, we show here that after portal venous injection, green fluorescent protein (GFP)-labeled TSCs survive for several months in the livers of allogeneic female but not male mice. Gonadectomy experiments revealed that this survival does not require the presence of ovarian hormones but does require the absence of testicular factors. By contrast, GFP-labeled allogeneic embryonic stem cells (ESCs) are reliably rejected; however, these same ESCs survive when mixed with unlabeled TSCs. The protective effect does not require immunological compatibility between ESCs and TSCs. Tumors were not observed in animals with either successfully engrafted TSCs or coinjected ESCs. We conclude that in a suitable hormonal context and location, ectopic TSCs can exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as a new model for studying trophoblast immunology and physiology.

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“…Several reports support these results. C-peptide (a precursor of insulin) expression was increased by the expression of TGF-1 and the viability and function of islet were also improved [23] and TGF-1 also stimulates insulin gene [28]. In order to evaluate the effect of Treg-derived TGF-1 on islet cell function in vivo transplantation, 180 IEQ of syngeneic islet cells (IT group) or 180 IEQ islet cells which were co-cultured with Treg (TCIT group; using the trans-well culture system, islet and Treg were not contacted directly)…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells Promote Pancreatic Islet Function and Viability via TGF-β1in vitroandin vivo

Choi

Kim

2018

Korean J Clin Lab Sci.

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Regulatory T cells (Treg), known as immune-suppressors, may help modulate the immune response. In this study, we investigated the effect of Treg-derived TGF-1 on pancreatic islet cell function in vitro and in vivo. One hundred eighty IEQ (islet equivalents) of pancreatic islets, the marginal amount to regulate blood glucose level after syngeneic islet transplantation in mouse type 1 diabetes (T1D) model, were co-cultured with 4×10 6 Treg cells for 48 hours. The changes in TGF-1, interleukin-6 (IL-6), and insulin secretion levels were measured and analyzed among the Treg-only group, the islet-only group, and the Treg/islet co-cultured group. In the Treg/islet co-cultured group, IL-6 and insulin secretion levels were increased (P＜ 0.0005, P＜ 0.005) and islet viability was improved (P＜0.005) compared with the islet-only group. Furthermore, after transplantation, the co-cultured islets regulated blood glucose levels efficiently in the T1D mouse model. These data suggest that Treg could improve islet functions and viability via the TGF-1 secretion pathway (P＜0.05∼0.005), thus the use of Treg in islet transplantation should be explored further.

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Expression of Transforming Growth Factor-β by Human Islets: Impact on Islet Viability and Function

Cited by 8 publications

References 40 publications

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function in Vitro

Human Fibroblast Sheet Promotes Human Pancreatic Islet Survival and Function in Vitro

Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

Regulatory T Cells Promote Pancreatic Islet Function and Viability via TGF-β1in vitroandin vivo

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