V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog A Synthetic Modified mRNA Drives Reprogramming of Human Pancreatic Duct-Derived Cells Into Insulin-Secreting Cells

Corritore, Elisa; Lee, Yong Syu; Pasquale, Valentina; Liberati, Diego; Hsu, Mei-Ju; Lombard, Catherine; Smissen, Patrick Van Der; Vetere, Amedeo; Bonner-Weir, Susan; Piemonti, Lorenzo; Sokal, Étienne; Lysy, Philippe A.

doi:10.5966/sctm.2015-0318

Cited by 14 publications

(13 citation statements)

References 69 publications

(105 reference statements)

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“…After incubation with a 14-day stepwise protocol, HDDCs acquired β-cell features, including insulin secretion capacities, yet not to the extent of glucose sensitivity. Ongoing work is evaluating the possibility of bringing HDDCs to functionality and diabetes-reversal potential in animal models (Corritore et al 2016).…”

Section: In Vitro Expansion Of Pancreatic Ductal Cellsmentioning

confidence: 99%

β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

Corritore

Lee

Sokal

et al. 2016

Therapeutic Advances in Endocrinology

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Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3-to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.

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Section: In Vitro Expansion Of Pancreatic Ductal Cellsmentioning

confidence: 99%

β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

Corritore

Lee

Sokal

et al. 2016

Therapeutic Advances in Endocrinology

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“…Figure 5 depicts the differences between cellular reprogramming and transdifferentiation. Depending on the cocktail of transcription factors expressed by the IVT mRNA and on the adult somatic cell type, reprogramming or transdifferentiation will be performed, and different lineages can be obtained [155,[244][245][246][247].…”

Section: Regenerative Medicine and Cell Engineeringmentioning

confidence: 99%

“…Transdifferentiation of somatic cells with IVT mRNA has been mainly focused on the generation of insulin secreting β-cells for type 1 diabetes patients [247][248][249], and on obtaining cardiomyocytes to regenerate the cardiac tissue after a heart attack [155]. mRNA is a promising tool for the delivery of factors targeting altered signaling pathways in the early hours of infarction, as well as to address experimental and clinical needs to regenerate cardiac tissue and cardiac function in ischemic heart disease.…”

Section: Regenerative Medicine and Cell Engineeringmentioning

confidence: 99%

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

et al. 2020

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The use of messenger RNA (mRNA) in gene therapy is increasing in recent years, due to its unique features compared to plasmid DNA: Transient expression, no need to enter into the nucleus and no risk of insertional mutagenesis. Nevertheless, the clinical application of mRNA as a therapeutic tool is limited by its instability and ability to activate immune responses; hence, mRNA chemical modifications together with the design of suitable vehicles result essential. This manuscript includes a revision of the strategies employed to enhance in vitro transcribed (IVT) mRNA functionality and efficacy, including the optimization of its stability and translational efficiency, as well as the regulation of its immunostimulatory properties. An overview of the nanosystems designed to protect the mRNA and to overcome the intra and extracellular barriers for successful delivery is also included. Finally, the present and future applications of mRNA nanomedicines for immunization against infectious diseases and cancer, protein replacement, gene editing, and regenerative medicine are highlighted.

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“…The functional β cells can secret insulin and C-peptide in response to glucose. Transplantation of the β cells into diabetic SCID-beige mice mitigated hyperglycemia through their functional glucose-responsive insulin secretion [ 115 ].…”

Section: Modrna Applications In Cell Differentiationmentioning

confidence: 99%

Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate

Wang

2021

IJMS

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Modified mRNA (modRNA)-based somatic reprogramming is an effective and safe approach that overcomes the genomic mutation risk caused by viral integrative methods. It has improved the disadvantages of conventional mRNA and has better stability and immunogenicity. The modRNA molecules encoding multiple pluripotent factors have been applied successfully in reprogramming somatic cells such as fibroblasts, mesenchymal stem cells, and amniotic fluid stem cells to generate pluripotent stem cells (iPSCs). Moreover, it also can be directly used in the terminal differentiation of stem cells and fibroblasts into functional therapeutic cells, which exhibit great promise in disease modeling, drug screening, cell transplantation therapy, and regenerative medicine. In this review, we summarized the reprogramming applications of modified mRNA in iPSC generation and therapeutic applications of functionally differentiated cells.

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V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog A Synthetic Modified mRNA Drives Reprogramming of Human Pancreatic Duct-Derived Cells Into Insulin-Secreting Cells

Cited by 14 publications

References 69 publications

β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells

Nanomedicines to Deliver mRNA: State of the Art and Future Perspectives

Application of Modified mRNA in Somatic Reprogramming to Pluripotency and Directed Conversion of Cell Fate

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