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Canonical Wnt signaling pathway contributes to the proliferation and survival in porcine pancreatic stem cells (PSCs)

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Abstract

Pancreatic stem cells (PSCs) transplantation is a potential therapeutic approach to type 1 diabetes mellitus (D1M). However, before clinical use, there are some major hurdles to be faced that need to be comprehensively considered and given some potential solutions in vitro. Human PSCs are difficult to obtain and have a short replicative senescence. As an alternative, we instead established porcine PSCs; as insulin is highly conserved and physiological glucose levels are similar between human and porcine. In order to solve the problems during transplantation therapy, such as the need for an enormous amount of PSCs and good cell survival in overactive autoimmunity induced by reactive oxygen cpecies (ROS) in D1M patients, we utilized Wnt3a overexpression to activate the canonical Wnt signaling pathway in PSCs. We found that the expression of proliferation genes, such as c-Myc, was up-regulated as the downstream of β-catenin, which promoted the PSCs proliferation and made cell numbers to meet the transplantation needs. We also showed that activation of the Wnt pathway made cells more readily tolerate ROS-caused mitochondria injury and cell apoptosis, thus making cells survive in autoimmune patients. The present study provides a theoretical basis for cell transplantation therapy of diabetes.

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Acknowledgment

This work was supported by grants from the National Natural Science Foundation of China (NSFC, 31101775).

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    Authors and Affiliations

    1. College of Veterinary Medicine, Shaanxi Centre of Stem Cells Engineering & Technology, Key Laboratory for Animal Biotechnology of Agriculture Ministry of China, Northwest A&F University, Yangling, Shaanxi, 712100, People’s Republic of China

      Xin He, Wei Han, Shu-xian Hu, Ming-zhi Zhang, Jin-lian Hua & Sha Peng

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    1. Xin He
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    2. Wei Han
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    3. Shu-xian Hu
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    4. Ming-zhi Zhang
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    5. Jin-lian Hua
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    6. Sha Peng
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    Corresponding authors

    Correspondence to Jin-lian Hua or Sha Peng.

    Additional information

    Xin He and Wei Han contributed equally to this work.

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    Figure S1

    Wnt3a was weakly expressed in the 6-month-old porcine pancreas tissue and showed a colocalization with Pdx1 observed by immunofluoresence analysis. (Hoe means Hoechst 33342). Bar 100 μm. Green Pdx1 expression (s1s1). Red Wnt3a expression (s1s1’). Blue Hoechst33342 staining for cell nucleus (s1s1”). ss”’ the merged image of s1s1, s1s1’ and s1s1”. (GIF 159 kb)

    High resolution image (TIFF 115 kb)

    Figure S2

    Tcf4N could abolish the Wnt3a-caused intracellular ROS reduced under the condition of treatment with or without H2O2. Tcf4N-transfected and control PSCs were exposed to hydrogen peroxide with or without LiCl, then stained with DCFH-DA to measure the intracellular ROS level by flow cytometry. *p < 0.05, LiCl(+) group compared with the empty control and LiCl (+) Tcf4N(+) groups. **p < 0.01, H2O2 (+) LiCl (+) group compared with the H2O2 (+) and H2O2 (+) LiCl (+) Tcf4N(+) groups. (GIF 146 kb)

    High resolution image (TIFF 69 kb)

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    He, X., Han, W., Hu, Sx. et al. Canonical Wnt signaling pathway contributes to the proliferation and survival in porcine pancreatic stem cells (PSCs). Cell Tissue Res 362, 379–388 (2015). https://doi.org/10.1007/s00441-015-2220-x

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    • DOI: https://doi.org/10.1007/s00441-015-2220-x

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