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Engineering pancreatic tissues from stem cells towards therapy.

Yoshinobu Takahashi1, Takanori Takebe1,2,3,4, Hideki Taniguchi1,2

  • 1Department of Regenerative Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku 3-9, Yokohama, Kanagawa, 236-0004, Japan.

Regenerative Therapy
|June 28, 2019
PubMed
Summary

Generating functional beta cells from stem cells is crucial for type 1 diabetes treatment. This review covers 2D and 3D differentiation methods, focusing on improving beta cell production for transplantation therapies.

Keywords:
2D, two-dimensional3D, three-dimensionalBMP, bone morphogenic proteinDiabetesES, embryonic stemFGF, fibroblast growth factorsHeterotypic cellular interactionIBMIR, instant blood-mediated reactionILV, indolactam VNgn3, neurogenin 3PEG, polyethylene glycolPI3K, phosphatidylinositol-3 kinasePIPAAm, poly-N-isopropylacrylamidePVA, polyvinyl alcoholPancreasPdx1, pancreatic and duodenal homeobox 1Ptf1a, pancreatic transcription factor 1aRegenerative medicineVEGF, vascular endothelial growth factorVascularizationiPS, induced pluripotent stemiPS/ES cell

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Area of Science:

  • Regenerative Medicine
  • Endocrinology
  • Developmental Biology

Background:

  • Pancreatic islet transplantation is a potential therapy for type 1 diabetes mellitus.
  • A major limitation is the scarcity of donor islets.
  • Advances in directed differentiation of pluripotent stem cells offer new avenues for beta cell generation.

Purpose of the Study:

  • To review recent progress in directed differentiation of pancreatic beta cells.
  • To compare two-dimensional (2D) and three-dimensional (3D) differentiation strategies.
  • To discuss transplantation and bioengineering approaches for diabetes therapy.

Main Methods:

  • Summarizing recent publications on directed beta cell differentiation protocols.
  • Focusing on methods recapitulating developmental cues using growth factors and small molecules.
  • Highlighting the role of spatiotemporal multicellular interactions in 3D culture.

Main Results:

  • Protocols for directed differentiation of embryonic stem (ES) and induced pluripotent stem (iPS) cells have been developed.
  • While efficiency has improved, in vitro functional beta cell differentiation remains challenging.
  • 3D culture systems show promise for recapitulating multicellular interactions.

Conclusions:

  • Directed differentiation holds promise for generating beta cells for type 1 diabetes treatment.
  • Further optimization of differentiation protocols, particularly in 3D settings, is needed.
  • Integration with bioengineering strategies is key for successful transplantation therapies.