Immunotherapy for type 1 diabetes

Frumento, Davide; Nasr, Moufida Ben; Essawy, Basset El; D’Addio, Francesca; Zuccotti, Gian Vincenzo

doi:10.1007/s40618-017-0641-y

Cited by 32 publications

(28 citation statements)

References 52 publications

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“…They have the potential to differentiate into mesenchymal tissue lineages, including bone, fat and muscle (8,9). Mesenchymal stem cells have been used to treat pancreatic endocrine dysfunction in type 1 diabetes and have considerable efficacy (10,11). Mesenchymal stem cells can inhibit the activation of T lymphocytes (12), and the proliferation of B lymphocytes (13) and natural killer cells (14).…”

Section: Introductionmentioning

confidence: 99%

Adipose‑derived mesenchymal stem cells ameliorate dibutyltin dichloride‑induced chronic pancreatitis by inhibiting the PI3K/AKT/mTOR signaling pathway

Sun

et al. 2020

Mol Med Report

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adipose-derived mesenchymal stem cells (aScs) play a positive role in tissue injury repair and regeneration. The aim of this study was to determine whether aScs could ameliorate chronic pancreatitis (cP) induced by the injection of dibutyltin dichloride (dBTc) and to elucidate its potential mechanisms. Furthermore, this study also explored whether there was a significant difference if the ASCs were injected via the inferior vena cava or the left gastric artery. cP was induced in rats by a single intravenous administration of dBTc, and the accumulation of collagen and apoptotic rates of pancreatic acinar cells were analyzed. according to the results, aScs markedly reduced dBTc-induced pancreatic damage and collagen deposition in the rat model of cP. Moreover, aScs significantly decreased pancreatic cell apoptosis by regulating the expression levels of caspase-3, BaX and Bcl-2. These effects were observed regardless of whether the injection was in the inferior vena cava or the left gastric artery. it was also found that the expression levels of phosphorylated Pi3K, aKT and mTor in pancreatic tissues of the dBTc-induced cP model group were significantly increased, while the expression levels of phosphorylated Pi3K, aKT and mTor in the two treatment groups were markedly decreased. aScs noticeably suppressed the Pi3K/aKT/mTor pathway in the pancreatic tissue of dBTc-induced cP. This study indicated that ASCs protect against pancreatic fibrosis by modulating the Pi3K/aKT/mTor pathway, and have the potential to be a new strategy for the treatment of cP in the future.

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Section: Introductionmentioning

confidence: 99%

Adipose‑derived mesenchymal stem cells ameliorate dibutyltin dichloride‑induced chronic pancreatitis by inhibiting the PI3K/AKT/mTOR signaling pathway

Sun

et al. 2020

Mol Med Report

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“…MSC and hematopoietic stem cell therapy have been used in clinical trials for the treatment of pancreatic disorders including type 1 diabetes. 11,12 Protective roles of MSCs are thought to be mediated through their paracrine secretion of growth factors having antiapoptotic, immunoregulatory, and angiogenic functions; cell-to-cell contact is also important. 13 White adipose tissue is a promising source of MSCs because of its ease of sampling and ability to be expanded to clinically useful cell numbers in a short period of time.…”

Section: Introductionmentioning

confidence: 99%

Adipose Stem Cell Therapy Mitigates Chronic Pancreatitis via Differentiation into Acinar-like Cells in Mice

et al. 2017

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The objective of this study was to assess the capacity of adipose-derived mesenchymal stem cells (ASCs) to mitigate disease progression in an experimental chronic pancreatitis mouse model. Chronic pancreatitis (CP) was induced in C57BL/6 mice by repeated ethanol and cerulein injection, and mice were then infused with 4 × 10 or 1 × 10 GFP ASCs. Pancreas morphology, fibrosis, inflammation, and presence of GFP ASCs in pancreases were assessed 2 weeks after treatment. We found that ASC infusion attenuated pancreatic damage, preserved pancreas morphology, and reduced pancreatic fibrosis and cell death. GFP ASCs migrated to pancreas and differentiated into amylase cells. In further confirmation of the plasticity of ASCs, ASCs co-cultured with acinar cells in a Transwell system differentiated into amylase cells with increased expression of acinar cell-specific genes including amylase and chymoB1. Furthermore, culture of acinar or pancreatic stellate cell lines in ASC-conditioned medium attenuated ethanol and cerulein-induced pro-inflammatory cytokine production in vitro. Our data show that a single intravenous injection of ASCs ameliorated CP progression, likely by directly differentiating into acinar-like cells and by suppressing inflammation, fibrosis, and pancreatic tissue damage. These results suggest that ASC cell therapy has the potential to be a valuable treatment for patients with pancreatitis.

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“…Diseases of the National Institutes of Health (UM1AI109565 and FY15ITN168), and BCCHRI. changes in immunity during such trials is limited (3); the search for biomarkers to stratify patients likely to respond to a given therapy and track changes in immune regulation is ongoing (4,9).…”

Section: Funding Jdrf (1-pnf-2015-113-q-r 2-par-2015-123-q-r 3-sramentioning

confidence: 99%

“…Monogenic mutations in FOXP3 resulting in a lack of functional Tregs lead to T1D (2), and several T1D risk alleles occur in Treg-associated genes (e.g., SNPs in CD25, PTPN2, and PTPN22) (1). Accordingly, multiple studies are testing whether immunotherapy-based methods to boost Treg function can prevent or delay T1D progression (1,3,4). For example, inflammatory cytokine blockade (e.g., ustekinumab, αIL-12/23p40; ref.…”

Section: Introductionmentioning

confidence: 99%