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The secretome obtained under hypoxic preconditioning from human adipose-derived stem cells exerts promoted anti-apoptotic potentials through upregulated autophagic process

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Abstract

Background

Hypoxic preconditioning (HP) is a stem cell preconditioning modality designed to augment the therapeutic effects of mesenchymal stem cells (MSCs). Although autophagy is expected to play a role in HP, very little is known regarding the relationship between HP and autophagy.

Methods and results

The adipose-derived stem cell (ASC)-secretome obtained under normoxia (NCM) and ASC-secretome obtained under HP (HCM) were obtained by culturing ASCs for 24 h under normoxic (21% partial pressure of O2) and hypoxic (1% partial pressure of O2) conditions, respectively. Subsequently, to determine the in vivo effects of HCM, each secretome was injected into 70% partially hepatectomized mice, and liver specimens were obtained. HCM significantly reduced the apoptosis of thioacetamide-treated AML12 hepatocytes and promoted the autophagic processes of the cells (P < 0.05). Autophagy blockage by either bafilomycin A1 or ATG5 siRNA significantly abrogated the anti-apoptotic effect of HCM (P < 0.05), demonstrating that HCM exerts its anti-apoptotic effect by promoting autophagy. The effect of HCM — reduction of cell apoptosis and promotion of autophagic process — was also demonstrated in a mouse model.

Conclusions

HP appears to induce ASCs to release a secretome with enhanced anti-apoptotic effects by promoting the autophagic process of ASCs.

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Data Availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

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Acknowledgements

We would like to thank Hye-Jung Kim for photoshop works that has made the manuscript understood intuitively. We also would like to thank Ji-Hye Park for her data processing and statistical works.

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Authors and Affiliations

  1. Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea

    Haeyeon Seo, Ho Joong Choi, Ok-Hee Kim, Ha Eun Hong & Say-June Kim

  2. Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea

    Haeyeon Seo, Ok-Hee Kim, Jung Hyun Park, Ha Eun Hong & Say-June Kim

  3. Department of Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Republic of Korea

    Jung Hyun Park

  4. Catholic Central Laboratory of Surgery, Department of Surgery, Division of Hepatobiliary pancreatic surgery. Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo- daero, Seocho-gu, 06591, Seoul, Republic of Korea

    Say-June Kim

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  1. Haeyeon Seo
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Contributions

Kim SJ was responsible for planning the study, data interpretation, and writing manuscript. Seo H, Kim OH also wrote the manuscript and performed in vitro experiments. Choi HJ, Park JH analyzed the data. Hong HE also performed the various in vitro and in vivo experiments.

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Correspondence to Say-June Kim.

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Animal studies were accomplished according to the guidelines of the Institute for Laboratory Animal Research in Korea (CUMC-2020-0095-01).

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Seo, H., Choi, H.J., Kim, OH. et al. The secretome obtained under hypoxic preconditioning from human adipose-derived stem cells exerts promoted anti-apoptotic potentials through upregulated autophagic process. Mol Biol Rep 49, 8859–8870 (2022). https://doi.org/10.1007/s11033-022-07736-z

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  • DOI: https://doi.org/10.1007/s11033-022-07736-z

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