Diabetes therapy by lentiviral hepatic insulin gene expression without transformation of liver

Jörns, Anne; Lenzen, Sigurd

doi:10.1007/s00125-008-0931-1

Cited by 6 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, much attention has been focused on the potential of bioengineered insulin-producing surrogate cells. [4][5][6][7] Several sources have been considered for the in vitro generation of insulin-producing cells including ex vivo expanded β-cells, 8 endocrine progenitor cells, 9 transdifferentiated or transduced liver or intestinal cells, 10,11 bone marrow mesenchymal stem cells, 12 and pluripotent embryonic stem cells (ESCs). 13,14 ESCs harbor great potential for future cell replacement therapy of diabetes (Figure 1) because they offer two unique features: availability in potentially unlimited numbers and the plasticity to generate any cell type of the body by in vitro differentiation.…”

Section: Introductionmentioning

confidence: 99%

Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?

et al. 2011

View full text Add to dashboard Cite

Embryonic stem cells (ESCs) harbor the potential to generate every cell type of the body by differentiation. The use of hESCs holds great promise for potential cell replacement therapies for degenerative diseases including diabetes mellitus. The recently discovered induced pluripotent stem cells (iPSCs) exhibit immense potential for regenerative medicine as they allow the generation of autologous cells tailored to the patients' immune system. Research for insulin-producing surrogate cells from ESCs has yielded highly controversial results, because many steps and factors in the differentiation process are currently still unknown. Thus, there is no consensus on common standard protocols. The protocols presently used established the differentiation from pluripotent cells toward pancreatic progenitor cells. However, none of the differentiation protocols reported to date have generated by exclusive in vitro differentiation sufficient numbers of insulin-producing cells meeting all essential criteria of a β-cell. The cells often lack the crucial function of regulated insulin secretion upon glucose stimulation. This review focuses on past and current approaches to the generation of insulin-producing cells from pluripotent sources, such as ESCs and iPSCs, and critically discusses the hurdles to be taken before insulin-secreting surrogate cells derived from these stem cells will be of clinical use in humans.

show abstract

Section: Introductionmentioning

confidence: 99%

Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?

et al. 2011

View full text Add to dashboard Cite

show abstract

“…37,38 Recent studies concerning liver-directed gene therapy revealed that basal insulin requirements for T1DM could be met using lentivirus-mediated furin-cleavable insulin gene delivery to hepatocytes. 39,40 This approach was aimed at obviating the need for longacting insulin analogs in diabetic patients. However, the use of constitutive promoters (e.g., CMV) to drive insulin gene expression in targeted tissues would make the construct unresponsive to the fluctuations in blood glucose levels and predispose the host to developing hypoglycemia.…”

Section: Introductionmentioning

confidence: 99%

Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes

et al. 2021

View full text Add to dashboard Cite

“…3 However, this approach is limited by the need for immune suppression and a shortage of donor tissue suitable for transplantation. Other sources of surrogate cells that have been considered include pluripotent embryonic stem cells, 4,5 ex vivo expansion of β-cells; 6 use of endocrine progenitor cells, 7 transdifferentiation of liver and intestinal cells 8,9 or bone marrow mesenchymal stem cells. 10 It is, however, now recognized that embryonic or bone marrow derived stem cells harbor the greatest potential for cell replacement strategy as they can be expanded to therapeutically relevant numbers and has the plasticity to generate most cell types of the body.…”

Section: Introductionmentioning

confidence: 99%

A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34+ Cells

Reebye

Sætrom

Mintz

et al. 2013

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Upon functional loss of insulin producing islet β-cells, some patients with diabetes become dependent on life-long insulin supplementation therapy. Bioengineering surrogate insulin producing cells is an alternative replacement strategy. We have developed a novel approach using short-activating RNA oligonucleotides to differentiate adult human CD34+ cells into insulin-secreting cells. By transfecting RNA to increase transcript levels of the master regulator of insulin biosynthesis, v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), several pancreatic endodermal genes were upregulated during the differentiation procedure. These included Pancreatic and duodenal homeobox gene-1 (PDX1), Neurogenin 3, NeuroD, and NK6 homeobox 1 (NKx6-1). Differentiated CD34+ cells also expressed glucokinase, glucagon-like peptide 1 receptor (GLP1R), sulfonylurea receptor-1 (SUR1) and phogrin—all essential for glucose sensitivity and insulin secretion. The differentiated cells appropriately processed C-peptide and insulin in response to increasing glucose stimulation as shown by enzyme-linked immunosorbent assay (ELISA), fluorescence-activated cell sorting analysis, western blotting, and immunofluorescence staining. We provide a new approach using short-activating RNA in developing insulin producing surrogate cells for treating diabetes.

show abstract

Diabetes therapy by lentiviral hepatic insulin gene expression without transformation of liver

Cited by 6 publications

References 7 publications

Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?

Insulin-producing Surrogate β-cells From Embryonic Stem Cells: Are We There Yet?

Lentivirus Mediated Pancreatic Beta-Cell-Specific Insulin Gene Therapy for STZ-Induced Diabetes

A Short-activating RNA Oligonucleotide Targeting the Islet β-cell Transcriptional Factor MafA in CD34+ Cells

Contact Info

Product

Resources

About