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Vector-free in vivo trans-determination of adult hepatic stem cells to insulin-producing cells

  • Shuvasree Sarkar
  • Chayan Munshi
  • Sarmishtha Chatterjee
  • Sandip Mukherjee
  • Shelley BhattacharyaEmail author
Short Communication
  • 34 Downloads

Abstract

A reduction in the number of functional β-cells is the central pathological event in diabetes. Liver and ventral pancreas differentiates simultaneously in the same general domain of cells within embryonic endoderm. In addition, the precursor cell population being bi-potential may be targeted for either pancreas or liver development. Hepatic stem cells were redirected in vivo to functional insulin producing cells in a acetylaminofluorene–partial hepatectomy (AAF/PH) adult male rat model with/without GLP-1 treatment. In routine H&E histology and immunohistochemistry, stem cells resembled β cells in GLP-1 injected rats. Immunoblots revealed involvement of adenylate cyclase, TLR4 and PDX1 in insulin synthesis. Expression of genes (GLP-1R, MAFA, PDX1, INS1 and INS2) augmented in the GLP-1 treated regenerated liver. Results strongly indicated the key role of GLP-1 in the induction of insulin secretion in trans-determined reprogrammed cell in vivo. The present method being vector free poses no risk of vector spillover in the host and holds promise.

Keywords

Stem cell β-Like cell GLP-1 Vector free trans-determination 

Notes

Acknowledgement

Authors gratefully acknowledge National Academy of Sciences, India for providing research grant in the NASI Honorary Scientist Scheme.

Authors contribution

All authors contributed equally in experimental design and manuscript preparation. SS contributed in hepatectomy, Western blotting and gene expression; CM contributed in histology and immunohistochemistry; SM contributed in FACS analysis.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Environmental Toxicology Laboratory, Department of Zoology, Centre for Advanced StudiesVisva-Bharati UniversitySantiniketanIndia
  2. 2.School of Environment and Life SciencesUniversity of SalfordSalfordUK
  3. 3.KolkataIndia
  4. 4.Molecular Endocrinology Laboratory, Department of Zoology, Centre for Advanced StudiesVisva-Bharati UniversitySantiniketanIndia

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