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Substances for regenerative wound healing during antler renewal stimulated scar-less restoration of rat cutaneous wounds

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Abstract

Scarification is the outcome of cutaneous wound healing under normal conditions. Although considerable effort has been expended in this field, scar-less healing has not been achieved satisfactorily. The lack of a good model of scar-free healing has contributed to this undesirable situation. However, the annual regeneration of deer antlers, which starts from regenerative wound healing over the top of the pedicles (permanent bony protuberances), may provide such a model. Therefore, in this study, we investigated the process of pedicle wound healing at the organ, tissue, cell, and molecular levels. Our results convincingly demonstrate that wounds over the pedicle preceded a regenerative healing process including regeneration of skin appendages, such as hair follicles. Compared to the scar healing in rats, regenerative healing of the pedicle wound exhibited a weaker inflammatory response, lack of myofibroblast induction, and higher ratios of Col III/Col I, TGF-β3/TGF-β1, and MMP/TIMP. Importantly, our periosteal transplantation experiments in vivo revealed that this regenerative healing process was achieved through induction of antler stem cells (ASCs). Further study showed that this effect of ASCs on regenerative healing was not species-specific but more generic and could be applied to other mammalian species, as injection of ASCs stimulated regenerative healing of full-thickness excisional cutaneous wounds in rats. Overall, our findings show that ASCs may have therapeutic potential in enhancing the quality of wound healing and preventing scar formation in clinical settings.

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Availability of data and materials

The transcriptome sequencing data for deer has been deposited in the Sequence Read Archive (SRA) database (https://www.ncbi.nlm.nih.gov/sra/) under accession number: SRR13407542; SRR13407538; SRR13407541; SRR13407543; SRR13407539; SRR13407540.

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Acknowledgements

We would like to thank Dr Peter Fennessy of AbacusBio Limited, Dunedin, New Zealand, for helping review the manuscript, and staff from the Deer Antler Research Group, Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, for the help of collection of antler stem cells.

Funding

This work was funded by the Technology Development Plan Project of Jilin Province (20200404004YY and 20190304006YY), Provincial Natural Science Foundation of Jilin (2020201031JC), National Natural Science Foundation of China (U20A20403 and 31901058), and National key Research and Development Project (2018YFC1706603-03).

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Authors and Affiliations

  1. Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), Changchun, Jilin, 130112, China

    Qianqian Guo, Zhen Liu, Junjun Zheng & Haiping Zhao

  2. Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, Jilin, 130600, China

    Chunyi Li

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  1. Qianqian Guo
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  4. Haiping Zhao
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Contributions

QG, CL, and HZ conceived and designed the experiment. QG and ZL performed the experiments. JZ, QG, and HZ performed bioinformatics and statistical analyses. QG and CL drafted the manuscript. HZ, JZ, and CL revised the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Haiping Zhao or Chunyi Li.

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This study was approved by the Animal Ethics Committee of Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences (Permit Number: NO.ISAPSAEC-2020–022).

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Guo, Q., Liu, Z., Zheng, J. et al. Substances for regenerative wound healing during antler renewal stimulated scar-less restoration of rat cutaneous wounds. Cell Tissue Res 386, 99–116 (2021). https://doi.org/10.1007/s00441-021-03505-9

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