Dataset Information

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

ABSTRACT:

Background

A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO₂) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined.

Methods

We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO₂ (21%, 10%, 5%, and 1%). Subsequently, partially hepatectomized mice were injected with the secretome of ASCs cultured under different pO₂, and then sera and liver specimens were obtained for analyses.

Results

Of all AML12 cells cultured under different pO₂, the AML12 cells cultured under 1% pO₂ showed the highest mRNA expression of proliferation-associated markers (IL-6, HGF, and VEGF). In the cell proliferation assay, the AML12 cells cultured with the secretome of 1% pO₂ showed the highest cell proliferation, followed by the cells cultured with the secretome of 21%, 10%, and 5% pO₂, in that order. When injected into the partially hepatectomized mice, the 1% pO₂ secretome most significantly increased the number of Ki67-positive cells, reduced serum levels of proinflammatory mediators (IL-6 and TNF-?), and reduced serum levels of liver transaminases. In addition, analysis of the liver specimens indicated that injection with the 1% pO₂ secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration.

Conclusions

The data of this study suggest that the secretome of ASCs cultured under 1% pO₂ has the highest liver reparative and regenerative potential of all the secretomes tested here.

SUBMITTER: Lee SC

PROVIDER: S-EPMC5543744 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

Lee Sang Chul SC Kim Kee-Hwan KH Kim Ok-Hee OH Lee Sang Kuon SK Hong Ha-Eun HE Won Seong Su SS Jeon Sang-Jin SJ Choi Byung Jo BJ Jeong Wonjun W Kim Say-June SJ

Stem cell research & therapy 20170803 1

<h4>Background</h4>A hypoxic-preconditioned secretome from stem cells reportedly promotes the functional and regenerative capacity of the liver more effectively than a control secretome. However, the optimum oxygen partial pressure (pO<sub>2</sub>) in the cell culture system that maximizes the therapeutic potential of the secretome has not yet been determined.<h4>Methods</h4>We first determined the cellular alterations in adipose tissue-derived stem cells (ASCs) cultured under different pO<sub>2 ...[more]

PMID: 28774345

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Project description:Background The therapeutic effects of adipose-derived mesenchymal stromal cells (ADSCs) may be mainly mediated by their paracrine effects. The ADSC-secretome can ameliorate hepatic ischemia–reperfusion injury (IRI). We explored the therapeutic effect of the ADSC-secretome from the perspective of excessive hepatocyte autophagy induced by hepatic IRI. Methods We established a miniature pig model of hepatic ischemia–reperfusion (I/R) and hepatectomy using a laparoscopic technique and transplanted ADSCs and the ADSC-secretome into the liver parenchyma immediately after surgery. Liver injury and hepatocyte autophagy were evaluated by histopathological examination and assessment of relevant cytokines and other factors. Results The results showed that the ADSC-secretome alleviated the pathological changes of liver tissue and the microstructural damage of hepatocytes after IRI. Moreover, the expression levels of autophagy-related markers including Beclin-1, ATG5, ATG12, and LC3II/LC3I decreased, whereas those of p62 increased during phagophore expansion. Furthermore, the expression levels of markers related to the autophagy inhibition pathway phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR), including PI3K, Akt, and mTOR, increased. Conclusion The ADSC-secretome attenuates hepatic I/R and hepatectomy-induced liver damage by inhibiting autophagy, which is possibly mediated by activation of the PI3K/Akt/mTOR signaling pathway. In addition, there was no significant difference between ADSCs and the ADSC-secretome in the regulation of hepatocyte autophagy. Therefore, ADSCs may improve the excessive autophagy-induced injury of hepatocytes in hepatic I/R and hepatectomy through paracrine effect. Our findings provide new insight into the therapeutic potential of cell-free products, which could replace cell therapy in liver diseases. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-03109-2.

Dataset Information

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

Background

Methods

Results

Conclusions

Publications

Determination of optimized oxygen partial pressure to maximize the liver regenerative potential of the secretome obtained from adipose-derived stem cells.

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