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Front Cell Dev Biol. 2020 Mar 26;8:197. doi: 10.3389/fcell.2020.00197. eCollection 2020.

Human Obesity Induces Dysfunction and Early Senescence in Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells.

Frontiers in cell and developmental biology

Sabena M Conley, LaTonya J Hickson, Todd A Kellogg, Travis McKenzie, Julie K Heimbach, Timucin Taner, Hui Tang, Kyra L Jordan, Ishran M Saadiq, John R Woollard, Busra Isik, Mohsen Afarideh, Tamar Tchkonia, James L Kirkland, Lilach O Lerman

Affiliations

  1. Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN, United States.
  2. Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, United States.
  3. Department of Surgery, Mayo Clinic, Rochester, MN, United States.
  4. Department of Immunology, Mayo Clinic, Rochester, MN, United States.
  5. Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, United States.

PMID: 32274385 PMCID: PMC7113401 DOI: 10.3389/fcell.2020.00197

Abstract

BACKGROUND: Chronic inflammatory conditions like obesity may adversely impact the biological functions underlying the regenerative potential of mesenchymal stromal/stem cells (MSC). Obesity can impair MSC function by inducing cellular senescence, a growth-arrest program that transitions cells to a pro-inflammatory state. However, the effect of obesity on adipose tissue-derived MSC in human subjects remains unclear. We tested the hypothesis that obesity induces senescence and dysfunction in human MSC.

METHODS: MSC were harvested from abdominal subcutaneous fat collected from obese and age-matched non-obese subjects (

RESULTS: Mean age was 59 ± 8 years, 66% were females. Obese subjects had higher body-mass index (BMI) than non-obese. MSC from obese subjects exhibited lower proliferative capacities than non-obese-MSC, suggesting decreased function, whereas their migration remained unchanged. Senescent cell burden and phenotype, manifested as

CONCLUSION: Human obesity triggers an early senescence program in adipose tissue-derived MSC. Thus, obesity-induced cellular injury may alter efficacy of this endogenous repair system and hamper the feasibility of autologous transplantation in obese individuals.

Copyright © 2020 Conley, Hickson, Kellogg, McKenzie, Heimbach, Taner, Tang, Jordan, Saadiq, Woollard, Isik, Afarideh, Tchkonia, Kirkland and Lerman.

Keywords: adipose tissue; cellular dysfunction; cellular senescence; mesenchymal stem cells; obesity

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