β‐Cell replacement as a treatment for type 1 diabetes: an overview of possible cell sources and current axes of research

Vieira, Andhira; Courtney, Monica; Druelle, Noémie; Avolio, Fabio; Napolitano, Tiziana; Hadzić, B; Navarro-Sanz, Sergi; Ben-Othman, Nouha; Collombat, Patrick

doi:10.1111/dom.12721

Cited by 13 publications

(11 citation statements)

References 81 publications

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“…One strategy for diabetes treatment is the conversion of α cells or other endocrine or exocrine pancreatic cell types into β cells (reviewed in ref. 6). Cell conversion has been achieved by overexpression or repression of certain transcription factors, such as Pdx1, Ngn3, MafA, Pax4, and Arx (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors

Pekrun¹,

Alencastro²,

Luo³

et al. 2019

JCI Insight

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Conflict of interest: KP and MAK are named on patent applications for AAV variants used in this paper. MAK has equity interests in LogicBio Therapeutics. MG has equity interests in Yecuris Corp., Ambys Medicines, and LogicBio Therapeutics. MH owns stock in Encellin and Viacyte Inc., receives research support from Eli Lily, and holds roles as consultant and member of the scientific advisory board for Semma Therapeutics and Encellin.

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Section: Introductionmentioning

confidence: 99%

Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors

Pekrun¹,

Alencastro²,

Luo³

et al. 2019

JCI Insight

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“…We also thought that the treatment of rReg2 post‐STZ may increase β‐cell turnover, subsequently alleviating the diabetes in mice. However, the result was largely negative (Supporting Information Figure S2), although consistent with β‐cell loss in adulthood appearing to be irreversible . Unlike the STZ model, humans experience relatively long‐term development of diabetes during which rReg2 therapy may still be beneficial to prevent further β‐cell loss after diabetes diagnosis.…”

Section: Discussionmentioning

confidence: 97%

Dimorphic autoantigenic and protective effects of Reg2 peptide in the treatment of diabetic β‐cell loss

Zhang

et al. 2019

Diabetes Obesity Metabolism

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Aims The potential effect of regenerating (Reg) proteins in the treatment of diabetes has been indicated in the past decade, but the clinical use of Reg proteins requires more advances in translational medicine. In the present study, we produced recombinant regenerating protein 2 (rReg2), to prove its protective effect against streptozocin (STZ)‐induced diabetes in BALB/c mice. Materials and Methods rReg2 was administrated in STZ‐induced diabetic mice. Blood glucose, body weight, serum insulin and islet β‐cell loss were determined. However, Reg2 has also been reported to serve as an autoantigen that induces autoimmune attacks on islets and aggravates diabetic development in non‐obese diabetic mice. To address this contradiction, complete Freund's adjuvant was injected to generate a model that was hypersensitive to Reg2. In this model, islet CD8 T‐cell infiltration, serum Reg2 antibody and interleukin (IL)‐4 and IL‐10, and splenic CD4+/interferon (IFN)‐γ+ T cells were determined. Results Direct rReg2 pretreatment preserved islet β‐cell mass against STZ and improved glycaemia, body weight and serum insulin content. The protection against cell death was further confirmed in cultured mouse islets and MIN6 cells. On the other hand, significant elevations of serum Reg2 antibody and splenic CD4+/IFN‐γ+ T cells, and decreases in serum IL‐4 and IL‐10 were detected in rReg2‐vaccinated mice, which may contribute to the accelerated diabetes. Interestingly, these mice, upon further rReg2 treatment, exhibited alleviated diabetic conditions with less islet CD8+ T‐cell infiltration. Conclusion rReg2 treatment ameliorated STZ‐induced diabetes in normal BALB/c mice. By contrast, rReg2 vaccination exacerbated, but further rReg2 treatment alleviated, the severity of STZ‐induced diabetes. Thus, the protective effect of rReg2 is predominant over the autoantigenic β‐cell destruction, supporting the potential of rReg2 in the clinical treatment of diabetes.

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“…Islet transplantation remains the only permanent treatment; however, it is complicated by the shortage of donors, required immunosuppression, and risk of tissue rejection. Due to these limitations, a new source of β cells for type 1 diabetes patients is needed (Jiang & Chen, 2017; Vieira et al, 2016), which will require advances in human stem cell technologies and biomanufacturing platforms.…”

Section: Introductionmentioning

confidence: 99%

Insulin production from hiPSC‐derived pancreatic cells in a novel wicking matrix bioreactor

Amini

Paluh

Xie

et al. 2020

Biotech & Bioengineering

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Clinical use of pancreatic β islets for regenerative medicine applications requires mass production of functional cells. Current technologies are insufficient for large‐scale production in a cost‐efficient manner. Here, we evaluate advantages of a porous cellulose scaffold and demonstrate scale‐up to a wicking matrix bioreactor as a platform for culture of human endocrine cells. Scaffold modifications were evaluated in a multiwell platform to find the optimum surface condition for pancreatic cell expansion followed by bioreactor culture to confirm suitability. Preceding scale‐up, cell morphology, viability, and proliferation of primary pancreatic cells were evaluated. Two optimal surface modifications were chosen and evaluated further for insulin secretion, cell morphology, and viable cell density for human‐induced pluripotent stem cell‐derived pancreatic cells at different stages of differentiation. Scale‐up was accomplished with uncoated, amine‐modified cellulose in a miniature bioreactor, and insulin secretion and cell metabolic profiles were determined for 13 days. We achieved 10‐fold cell expansion in the bioreactor along with a significant increase in insulin secretion compared with cultures on tissue culture plastic. Our findings define a new method for expansion of pancreatic cells a on wicking matrix cellulose platform to advance cell therapy biomanufacturing for diabetes.

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β‐Cell replacement as a treatment for type 1 diabetes: an overview of possible cell sources and current axes of research

Cited by 13 publications

References 81 publications

Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors

Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors

Dimorphic autoantigenic and protective effects of Reg2 peptide in the treatment of diabetic β‐cell loss

Insulin production from hiPSC‐derived pancreatic cells in a novel wicking matrix bioreactor

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