4.7 Article

Senescing Human Bone-Marrow-Derived Clonal Mesenchymal Stem Cells Have Altered Lysophospholipid Composition and Functionality

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 13, Issue 3, Pages 1438-1449

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/pr400990k

Keywords

human clonal mesenchymal stem cells; cellular senescence; lysophosphatidylcholine; lysophosphatidylethanolamine

Funding

  1. Health Fellowship Foundation
  2. Korean government (MEST) [2011-0019639, 2011-0019634, 2009-0083533]
  3. National Research Foundation of Korea (NRF)
  4. Korea government (MSIP) [2011-0030810]
  5. National Research Foundation of Korea [2011-0019634, 2011-0019639] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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Mesenchyrnal stem cells (MSCs) have been used in a wide range of research and clinical studies because MSCs do not have any ethical issues and have the advantage of low carcinogenicity due to their limited proliferation. However, because only a small number of MSCs can be obtained from the bone marrow, ex vivo amplification is inevitably required. For that reason, this study was conducted to acquire the metabolic information to examine and control the changes in the activities and differentiation potency of MSCs during the ex vivo culture process. Endogenous metabolites of human bone-marrow-derived clonal MSCs (hcMSCs) during cellular senescence were profiled by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOFMS). To select significant metabolites, we used the linear mixed effects model having fixed effects for batch and time (passage) and random effects for metabolites, determining the mean using a t test and the standard deviation using an F test. We used structural analysis with representative standards and spectrum patterns with different collision energies to distinctly identify eight metabolites with altered expression during senescence as types of lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE), such as LPC 16:0 and LPE 22:4. The present study revealed changes in endogenous metabolites and mechanisms due to senescence.

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