Dataset Information

Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model.

ABSTRACT:

Objectives

Adipose tissue-derived mesenchymal stromal cells (ASCs) are useful in cell-based therapy. However, it is well known that diabetes mellitus (DM) alters ASCs' functionality. The majority of in vitro studies related to ASCs are developed under non-physiological oxygen conditions. Therefore, they may not reflect the full effects of DM on ASCs, in vivo. The main aim of the current study is to identify molecular pathways and underlying biological mechanisms affected by diabetes on ASCs in physiological oxygen conditions.

Materials and methods

ASCs derived from healthy (ASCs-C) and diabetic (ASCs-D) rats were expanded under standard culture conditions (21% O₂) or cultured in physiological oxygen conditions (3% O₂) and characterized. Differential gene expressions (DEGs) of ASCs-D with respect to ASCs-C were identified and analyzed with bioinformatic tools. Protein-protein interaction (PPI) networks, from up- and down-regulated DEGs, were also constructed.

Results

The bioinformatic analysis revealed 1354 up-regulated and 859 down-regulated DEGs in ASCs-D, with 21 and 78 terms over and under-represented, respectively. Terms linked with glycosylation and ribosomes were over-represented and terms related to the activity of RNA-polymerase II and transcription regulation were under-represented. PPI network disclosed RPL11-RPS5 and KDR-VEGFA as the main interactions from up- and down-regulated DEGs, respectively.

Conclusion

These results provide valuable information about gene pathways and underlying molecular mechanisms by which diabetes disturbs ASCs biology in physiological oxygen conditions. Furthermore, they reveal, molecular targets to improve the use of ASCs in autologous transplantation.

SUBMITTER: Paco-Meza LM

PROVIDER: S-EPMC9124531 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model.

Paco-Meza Luis-Miguel LM Carmona MDolores M Cañadillas Sagrario S Lopez-Diaz Ana A Muñoz-López Francisco F Jimenez-Arranz Alvaro A Guler Ipek I Herrera Concha C

Iranian journal of basic medical sciences 20220201 2

<h4>Objectives</h4>Adipose tissue-derived mesenchymal stromal cells (ASCs) are useful in cell-based therapy. However, it is well known that diabetes mellitus (DM) alters ASCs' functionality. The majority of <i>in vitro</i> studies related to ASCs are developed under non-physiological oxygen conditions. Therefore, they may not reflect the full effects of DM on ASCs, <i>in vivo</i>. The main aim of the current study is to identify molecular pathways and underlying biological mechanisms affected by ...[more]

PMID: 35655589

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Project description:IntroductionSilk fibroin (SF) scaffolds have been shown to be a suitable substrate for tissue engineering and to improve tissue regeneration when cellularized with mesenchymal stromal cells (MSCs). We here demonstrate, for the first time, that electrospun nanofibrous SF patches cellularized with human adipose-derived MSCs (Ad-MSCs-SF), or decellularized (D-Ad-MSCs-SF), are effective in the treatment of skin wounds, improving skin regeneration in db/db diabetic mice.MethodsThe conformational and structural analyses of SF and D-Ad-MSCs-SF patches were performed by scanning electron microscopy, confocal microscopy, Fourier transform infrared spectroscopy and differential scanning calorimetry. Wounds were performed by a 5 mm punch biopsy tool on the mouse's back. Ad-MSCs-SF and D-Ad-MSCs-SF patches were transplanted and the efficacy of treatments was assessed by measuring the wound closure area, by histological examination and by gene expression profile. We further investigated the in vitro angiogenic properties of Ad-MSCs-SF and D-Ad-MSCs-SF patches by affecting migration of human umbilical vein endothelial cells (HUVECs), keratinocytes (KCs) and dermal fibroblasts (DFs), through the aortic ring assay and, finally, by evaluating the release of angiogenic factors.ResultsWe found that Ad-MSCs adhere and grow on SF, maintaining their phenotypic mesenchymal profile and differentiation capacity. Conformational and structural analyses on SF and D-Ad-MSCs-SF samples, showed that sterilization, decellularization, freezing and storing did not affect the SF structure. When grafted in wounds of diabetic mice, both Ad-MSCs-SF and D-Ad-MSCs-SF significantly improved tissue regeneration, reducing the wound area respectively by 40% and 35%, within three days, completing the process in around 10 days compared to 15-17 days of controls. RT2 gene profile analysis of the wounds treated with Ad-MSCs-SF and D-Ad-MSCs-SF showed an increment of genes involved in angiogenesis and matrix remodeling. Finally, Ad-MSCs-SF and D-Ad-MSCs-SF co-cultured with HUVECs, DFs and KCs, preferentially enhanced the HUVECs' migration and the release of angiogenic factors stimulating microvessel outgrowth in the aortic ring assay.ConclusionsOur results highlight for the first time that D-Ad-MSCs-SF patches are almost as effective as Ad-MSCs-SF patches in the treatment of diabetic wounds, acting through a complex mechanism that involves stimulation of angiogenesis. Our data suggest a potential use of D-Ad-MSCs-SF patches in chronic diabetic ulcers in humans.

Dataset Information

Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model.

Objectives

Materials and methods

Results

Conclusion

Publications

Identification of molecular pathways and protein-protein interactions in adipose tissue-derived mesenchymal stromal cells (ASCs) under physiological oxygen concentration in a diabetic rat model.

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