Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function

Takako Izumoto-Akita, Shin Tsunekawa, Akihito Yamamoto, Eita Uenishi, Kota Ishikawa, Hidetada Ogata, Atsushi Iida, Makoto Ikeniwa, Kaori Hosokawa, Yasuhiro Niwa, Ryuya Maekawa, Yuichiro Yamauchi, Yusuke Seino, Yoji Hamada, Hideharu Hibi, Hiroshi Arima, Minoru Ueda, Yutaka Oiso

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Abstract

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 SHEDCM and serum-free conditioned media from human bone marrow-derived mesenchymal stem cells (BMCM) 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 SHEDCM enhanced insulin secretion in a glucose concentration-dependent manner and reduced STZinduced 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.

Original languageEnglish
Article numbere000128
JournalBMJ Open Diabetes Research and Care
Volume3
Issue number1
DOIs
Publication statusPublished - 19-10-2015

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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    Izumoto-Akita, T., Tsunekawa, S., Yamamoto, A., Uenishi, E., Ishikawa, K., Ogata, H., Iida, A., Ikeniwa, M., Hosokawa, K., Niwa, Y., Maekawa, R., Yamauchi, Y., Seino, Y., Hamada, Y., Hibi, H., Arima, H., Ueda, M., & Oiso, Y. (2015). Secreted factors from dental pulp stem cells improve glucose intolerance in streptozotocin-induced diabetic mice by increasing pancreatic β-cell function. BMJ Open Diabetes Research and Care, 3(1), [e000128]. https://doi.org/10.1136/bmjdrc-2015-000128