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Reseeding endothelial cells with fibroblasts to improve the re-endothelialization of pancreatic acellular scaffolds

Abstract

Pancreatic transplantation remains the only cure for diabetes, but the shortage of donors limits its clinical application. Whole organ decellularized scaffolds offer a new opportunity for pancreatic organ regeneration; however inadequate endothelialization and vascularization can prevent sufficient transport of oxygen and nutrient supplies to the transplanted organ, as well as leading unwanted thrombotic events. In the present study, we explored the re-endothelialization of rat pancreatic acellular scaffolds via circulation perfusion using human skin fibroblasts (FBs) and human umbilical vein endothelial cells (HUVECs). Our results revealed that the cell adhesion rate when these cells were co-cultured was higher than under control conditions, and this increase was associated with increased release of growth factors including VEGF, FGFb, EGF, and IGF-1 as measured by ELISA. When these recellularized organs were implanted in vivo for 28 days in rat dorsal subcutaneous pockets, we found that de novo vasculature formation in the co-culture samples was superior to the control samples. Together these results suggest that endothelial cell and FB co-culture enhances the re-endothelialization and vascularization of pancreatic acellular scaffolds.

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Acknowledgements

This research was supported by the National Key Research and Development Program of China (Grant no. 2018YFC1105603, 2017YFA0701304) and the National Natural Science Foundation of China (Grant no. 31830028, 81671823, 81471801), Science and Technology Project of Nantong City (MS12018077).

Author contributions

The authors thank Lu Jingjing at Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, for technical help with H&E staining and microscopy. XL and HY contributed to study design, data acquisition and article writing. WZ and ZS contributed to data interpretation and article editing. WD designed the research and edited the article. YY and GY contributed to study design, article editing and funding acquisition. XL and GY are the guarantors of this work, had full access to all the data in the study, and take responsibility for the data and the accuracy of the data analysis. All authors have approved the final version of the article.

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Correspondence to Yumin Yang or Yibing Guo.

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All animal procedures were performed according to institutional and national guidelines and approved by the Animal Care Ethics Committee of Nantong University.

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Xu, L., Huang, Y., Wang, D. et al. Reseeding endothelial cells with fibroblasts to improve the re-endothelialization of pancreatic acellular scaffolds. J Mater Sci: Mater Med 30, 85 (2019). https://doi.org/10.1007/s10856-019-6287-x

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