Microarray Analysis of Human Adipose-derived Adult Stem Cells Undergoing Osteogenic differentiation in the Presence and Absence of 10% Uniaxial Cyclic Tensile Strain

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Title: Microarray Analysis of Human Adipose-derived Adult Stem Cells Undergoing Osteogenic differentiation in the Presence and Absence of 10% Uniaxial Cyclic Tensile Strain
Author: Charoenpanich, Adisri
Advisors: Elizabeth G. Loboa, Committee Chair
Albert J. Banes, Committee Member
Greg McCarty, Committee Member
Abstract: Human adipose derived stem cells (hASCs) have shown great potential for bone tissue engineering. However, the molecular mechanisms underlying this potential are not yet known, in particular the effects of mechanical loading which is known to play a pivotal role in bone remodeling and bone fracture repair. This study aimed to develop understanding of osteogenic differentiation and mechanical response properties of hASCs for potential use in optimizing and controlling hASCs for bone tissue engineering or cell based therapy. Gene expression profiles of hASCs were examined using cDNA microarray with 47,000 gene identifiers. Three dimension collagen type I matrix was used as a culture system for mimicking the collagenous micro-environment of bone tissue. To investigate the regulation of osteogenesis of hASCs, gene expression profiles of hASCs cultured in osteogenic induction media were compared to proliferating hASCs in complete growth media for 14 days. The effect of mechanical loading on hASCs during osteogenesis was determined by comparing between hASCs cultured in osteogenic induction media in the presence and absence of 10% uniaxial cyclic tensile strain for up to 14 days. 847 genes were significantly modulated by osteogenic induction media, and 147 genes were significantly modulated by 10% uniaxial cyclic tensile strain. For osteogenesis of hASCs, 95 canonical pathways were identified as affected with the details of upregulated and downregulated genes for continuing molecular characterization. Some pathways were examined and showed the potential role in osteogenesis of hASCs including Wnt/β-catenin signaling, transforming growth factor- β (TGF- β) signaling, platelet derived growth factor (PDGF) signaling, and insulin-like growth factor 1 (IGF-1) signaling. To validate the microarray data, RT-PCR was performed to confirm changes in corin mRNA expression levels. To identify the effect of 10% uniaxial cyclic tensile strain, canonical pathway, function, and network analyses were performed. The function analysis showed the potential role of 10% uniaxial cyclic tensile strain in angiogenic induction on hASCs during osteogenesis. Twelve canonical pathways were provided with details for further analysis. Network analysis indicated interleukin 1 receptor antagonist (IL1RN), and suppressor of cytokine signaling 3 (SOCS3) as the potential key factors in response to mechanical loading in hASCs. The results of this study indicate multiple candidate genes and pathways that may play a role in the response of hASCs to osteogenesis and cyclic tensile strain, thus providing further understanding for the development of tissue-engineered bone using these relatively accessible and abundant adult stem cells.
Date: 2010-04-20
Degree: MS
Discipline: Biomedical Engineering
URI: http://www.lib.ncsu.edu/resolver/1840.16/6274


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