Abstract

Introduction. Mesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biologic aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived from adipose tissue (ASCs) and bone marrow (BMSCs) from young and old human donors were investigated by using an unbiased genome-wide approach.

Methods. Human ASCs and BMSCs from young and old donors were cultured, and total RNA was isolated. The miRNA fraction was enriched and used to determine the expression profile of miRNA in young and old donor MSCs. Based on miRNA expression, differences in donor MSCs were further investigated by using differentiation assays, Western blot, immunocytochemistry, and bioinformatics.

Results: Biologic aging demonstrated reduced osteogenic and adipogenic potential in ASCs isolated from older donors, whereas cell size, complexity, and cell-surface markers remained intact with aging. Analysis of miRNA profiles revealed that small subsets of active miRNAs changed secondary to aging. Evaluation of miRNA showed significantly decreased levels of gene expression of inhibitory kappa B kinase (IκB), interleukin-1α, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase/p38, ERK1/2, c-fos, and c-jun in MSCs from older donors by both bioinformatics and Western blot analysis. Nuclear factor kappa B (NF-κB), myc, and interleukin-4 receptor mRNA levels were significantly elevated in aged cells from both the adipose and bone marrow depots. Immunocytochemistry showed nuclear localization in young donors, but a cytosolic predominance of phosphorylated NF-κB in ASCs from older donors. Western blot demonstrated significantly elevated levels of NF-κB subunits, p65 and p50, and AKT.

Conclusions: These findings suggest that differential expression of miRNA is an integral component of biologic aging in MSCs.

Department(s)

Biological Sciences

Keywords and Phrases

Canonic Pathway; miRNA Profile; Young Donor; Relative Fold Change; Adipogenic Lineage

International Standard Serial Number (ISSN)

1757-6512

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2011 Pandey et al., All rights reserved.

PubMed ID

22169120

Included in

Biology Commons

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