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Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function
  1. Takako Izumoto-Akita1,2,
  2. Shin Tsunekawa1,
  3. Akihito Yamamoto2,
  4. Eita Uenishi1,
  5. Kota Ishikawa1,
  6. Hidetada Ogata1,
  7. Atsushi Iida1,
  8. Makoto Ikeniwa1,
  9. Kaori Hosokawa1,
  10. Yasuhiro Niwa1,
  11. Ryuya Maekawa1,
  12. Yuichiro Yamauchi1,
  13. Yusuke Seino3,
  14. Yoji Hamada3,
  15. Hideharu Hibi2,
  16. Hiroshi Arima1,
  17. Minoru Ueda2,
  18. Yutaka Oiso1
  1. 1Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  2. 2Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  3. 3Department of Metabolic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan
  1. Correspondence to Dr Shin Tsunekawa; tsune87{at}


Objective Many studies have reported that stem cell transplantation promotes propagation and protection of pancreatic β-cells in streptozotocin (STZ)-induced diabetic mice without the differentiation of transplanted cells into pancreatic β-cells, suggesting that the improvement is due to a paracrine effect of the transplanted cells. We investigated the effects of factors secreted by dental pulp stem cells from human exfoliated deciduous teeth (SHED) on β-cell function and survival.

Research design and methods Conditioned medium from SHED (SHED-CM) was collected 48 h after culturing in serum-free Dulbecco's modified Eagle's medium (DMEM). The insulin levels in SHED-CM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BM-CM) were undetectable. STZ-induced diabetic male C57B/6J mice were injected with DMEM as a control, SHED-CM, exendin-4 (Ex-4), or BM-CM for 14 days. Mouse pancreatic β-cell line MIN6 cells were incubated with different concentrations of STZ with SHED-CM, DMEM, Ex-4, or BM-CM for 6 h.

Results Administration of 1 mL of SHED-CM twice a day improved glucose intolerance in STZ-induced diabetic mice and the effect continued for 20 days after the end of treatment. SHED-CM treatment increased pancreatic insulin content and β-cell mass through proliferation and an intraperitoneal glucose tolerance test revealed enhanced insulin secretion. Incubation of MIN6 cells (a mouse pancreatic β-cell line) with SHED-CM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZ-induced cell death, indicating that the amelioration of hyperglycemia was caused by the direct effects of SHED-CM on β-cell function and survival. These effects were more pronounced than with the use of Ex-4, a conventional incretin-based drug, and BM-CM, which is a medium derived from other stem cells.

Conclusions These findings suggest that SHED-CM provides direct protection and encourages the propagation of β-cells, and has potential as a novel strategy for treatment of diabetes.

  • Beta Cell Secretion
  • Beta Cell(s)
  • Proliferation
  • Beta Cell Function

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