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Feline Adipose Derived Multipotent Stromal Cell Transdifferentiation Into Functional Insulin Producing Cell Clusters.

Takashi Taguchi1, Wei Duan1, Wendy Wolfson2

  • 1Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, United States.

Frontiers in Bioengineering and Biotechnology
|June 30, 2022
PubMed
Summary

Researchers generated functional insulin-producing cell (IPC) clusters from feline stem cells for diabetes treatment. Dynamic culture enhanced IPC functionality, offering a potential therapy for feline and human diabetes mellitus.

Keywords:
beta cell (β-cell)diabetesendocrineglucosepancreasstem cell

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Area of Science:

  • Regenerative Medicine
  • Endocrinology
  • Stem Cell Biology

Background:

  • Feline diabetes mellitus (DM) is a common endocrine disorder in cats.
  • Current treatments are often palliative, highlighting the need for novel therapeutic strategies.
  • Transdifferentiation of adipose-derived multipotent stromal cells (ASCs) offers a promising avenue for generating insulin-producing cells (IPCs).

Purpose of the Study:

  • To investigate the de novo generation of functional feline IPC clusters from ASCs.
  • To evaluate the potential of these IPCs as a cell therapy for feline DM.
  • To explore the feasibility of this approach for developing comparable human treatments.

Main Methods:

  • Feline ASCs were cultured using a novel three-stage process in stromal or differentiation medium under static and dynamic conditions.
  • Induced IPC clusters were assessed for viability, intracellular zinc, insulin, glucagon, somatostatin, and ultrastructure.
  • Glucose-stimulated insulin secretion, protein, and gene expression were analyzed.

Main Results:

  • IPC clusters cultured in differentiation medium exhibited robust viability, contained zinc, and expressed insulin, glucagon, and somatostatin.
  • Ultrastructural analysis revealed insulin granules, and clusters demonstrated glucose-dependent insulin secretion.
  • Dynamic culture conditions enhanced IPC functionality, leading to higher insulin secretion compared to static cultures.

Conclusions:

  • Functional feline IPC clusters can be generated from ASCs, supporting their potential as a cell therapy for feline DM.
  • Dynamic culture conditions, utilizing motion-driven shear stress, significantly enhance IPC cluster functionality.
  • This study provides a foundation for developing IPC-based therapies for diabetes across species.