Adipose-derived stem cells from lean and obese humans show depot specific differences in their stem cell markers, exosome contents and senescence: role of protein kinase C delta (PKCδ) in adipose stem cell niche

瘦人和肥胖人的脂肪干细胞在干细胞标志物、外泌体含量和衰老方面表现出特定的差异:蛋白激酶 C delta (PKCδ) 在脂肪干细胞微环境的作用

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作者:Rekha S Patel, Gay Carter, Ghattas El Bassit, Achintya A Patel, Denise R Cooper, Michel Murr, Niketa A Patel

Background

Adipose-derived stem cells (ASC) and its exosomes are gaining utmost importance in the field of regenerative medicine. The ASCs tested for their potential in wound healing are predominantly derived from the subcutaneous depot of lean donors. However, it is important to characterize the ASC derived from different adipose depots as these depots have clinically distinct roles.

Conclusions

Our case-specific study demonstrates a role of PKCδ in maintaining the adipose stem cell niche and importantly demonstrates depot-specific differences in adipose stem cells and their exosome content.

Methods

We characterized the ASC derived from subcutaneous and omental depots from a lean donor (sc-ASCn and om-ASCn) and compared it to the ASC derived from an obese donor (sc-ASCo and om-ASCo) using flow cytometry and real time qPCR.

Results

We show that stem cell markers Oct4, Sal4, Sox15, KLF4 and BMI1 have distinct expression patterns in each ASC. We evaluated the secretome of the ASC and characterized their secreted exosomes. We show long noncoding RNAs (lncRNAs) are secreted by ASC and their expression varied between the ASC's derived from different depots. Protein kinase C delta (PKCδ) regulates the mitogenic signals in stem cells. We evaluated the effect of silencing PKCδ in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Using β-galactosidase staining, we evaluated the percentage of senescent cells in sc-ASCn, om-ASCn, sc-ASCo and om-ASCo. Our results also indicated that silencing PKCδ increases the percentage of senescent cells. Conclusions: Our case-specific study demonstrates a role of PKCδ in maintaining the adipose stem cell niche and importantly demonstrates depot-specific differences in adipose stem cells and their exosome content.

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