Improved physiological properties of gravity-enforced reassembled rat and human pancreatic pseudo-islets

J Tissue Eng Regen Med. 2017 Jan;11(1):109-120. doi: 10.1002/term.1891. Epub 2014 Apr 16.


Previously we demonstrated the superiority of small islets vs large islets in terms of function and survival after transplantation, and we generated reaggregated rat islets (pseudo-islets) of standardized small dimensions by the hanging-drop culture method (HDCM). The aim of this study was to generate human pseudo-islets by HDCM and to evaluate and compare the physiological properties of rat and human pseudo-islets. Isolated rat and human islets were dissociated into single cells and incubated for 6-14 days by HDCM. Newly formed pseudo-islets were analysed for dimensions, morphology, glucose-stimulated insulin secretion (GSIS) and total insulin content. The morphology of reaggregated human islets was similar to that of native islets, while rat pseudo-islets had a reduced content of α and δ cells. GSIS of small rat and human pseudo-islets (250 cells) was increased up to 4.0-fold (p < 0.01) and 2.5-fold (p < 0.001), respectively, when compared to their native counterparts. Human pseudo-islets showed a more pronounced first-phase insulin secretion as compared to intact islets. GSIS was inversely correlated to islet size, and small islets (250 cells) contained up to six-fold more insulin/cell than large islets (1500 cells). Tissue loss with this new technology could be reduced to 49.2 ± 1.5% in rat islets, as compared to the starting amount. With HDCM, pseudo-islets of standardized size with similar cellular composition and improved biological function can be generated, which compensates for tissue loss during production. Transplantation of small pseudo-islets may represent an attractive strategy to improve graft survival and function, due to better oxygen and nutrient supply during the phase of revascularization. Copyright © 2014 John Wiley & Sons, Ltd.

Keywords: diabetes; hanging drop; islet cell transplantation; pseudo-islets; reaggregation; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Aggregation
  • Cell Culture Techniques / methods*
  • Cells, Cultured
  • Glucose / chemistry
  • Graft Survival
  • Gravitation
  • Humans
  • Insulin / chemistry*
  • Insulin-Secreting Cells / cytology
  • Islets of Langerhans / cytology*
  • Male
  • Oxygen / chemistry
  • Perfusion
  • Rats
  • Rats, Inbred Lew


  • Insulin
  • Glucose
  • Oxygen