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Home / Equine Research Bank / Stem Cell Res Ther / Age-dependent impairment of adipose-derived stem cells isola...
Stem cell research & therapy2020; 11(1); 4; doi: 10.1186/s13287-019-1512-6

Age-dependent impairment of adipose-derived stem cells isolated from horses.

Abstract: Progressive loss of cell functionality caused by an age-related impairment in cell metabolism concerns not only mature specialized cells but also its progenitors, which significantly reduces their regenerative potential. Adipose-derived stem cells (ASCs) are most commonly used in veterinary medicine as an alternative treatment option in ligaments and cartilage injuries, especially in case of high-value sport horses. Therefore, the main aim of this study was to identify the molecular alternations in ASCs derived from three age-matched horse groups: young ( 15 years old). ASCs were isolated from three age-matched horse groups using an enzymatic method. Molecular changes were assessed using qRT-PCR, ELISA and western blot methods, flow cytometry-based system, and confocal and scanning electron microscopy. Our findings showed that ASCs derived from the middle-aged and old groups exhibited a typical senescence phenotype, such as increased percentage of G1/G0-arrested cells, binucleation, enhanced β-galactosidase activity, and accumulation of γH2AX foci, as well as a reduction in cell proliferation. Moreover, aged ASCs were characterized by increased gene expression of pro-inflammatory cytokines and miRNAs (interleukin 8 (IL-8), IL-1β, tumor necrosis factor α (TNF-α), miR-203b-5p, and miR-16-5p), as well as apoptosis markers (p21, p53, caspase-3, caspase-9). In addition, our study revealed that the protein level of mitofusin 1 (MFN1) markedly decreased with increasing age. Aged ASCs also displayed a reduction in mRNA levels of genes involved in stem cell homeostasis and homing, like TET-3, TET-3 (TET family), and C-X-C chemokine receptor type 4 (CXCR4), as well as protein expression of DNA methyltransferase (DNMT1) and octamer transcription factor 3/4 (Oct 3/4). Furthermore, we observed a higher splicing ratio of XBP1 (X-box binding protein 1) mRNA, indicating elevated inositol-requiring enzyme 1 (IRE-1) activity and, consequently, increased endoplasmic reticulum (ER) stress. We also observed reduced levels of glucose transporter 4 (GLUT-4) and insulin receptor (INSR) which indicated impaired insulin sensitivity. Obtained data suggest that ASCs derived from horses older than 5 years old exhibited several molecular alternations which markedly limit their regenerative capacity. The results provide valuable information that allows for a better understanding of the molecular events occurring in ASCs in the course of aging and may help to identify new potential drug targets to restore their regenerative potential.
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Publication Date: 2020-01-03 PubMed ID: 31900232PubMed Central: PMC6942290DOI: 10.1186/s13287-019-1512-6Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigated how aging influences the functioning of adipose-derived stem cells (ASCs) in horses, and the research found that the regenerative capacity of these stem cells decreases with age due to various molecular changes.

Objective and Methodology

  • The objective of this research was to assess how the regenerative abilities of adipose-derived stem cells (ASCs) are influenced by age in horses. This is important because ASCs play a crucial role in treating ligament and cartilage injuries in animals, particularly high-value sport horses.
  • ASCs were obtained from horses across three age groups: young (under 5 years), middle-aged (5-15 years), and old (over 15 years).
  • An enzymatic method was used to isolate the ASCs, and molecular changes in the cells were evaluated using several techniques, including quantitative reverse transcription PCR (qRT-PCR), enzyme-linked immunoassay (ELISA), and western blot methods.
  • These techniques allowed the researchers to investigate various indicators of senescence, inflammation, apoptosis, stem cell homeostasis, and cellular stress.

Findings

  • The study found that ASCs from middle-aged and old horses showed typical signs of aging at the cellular level, such as an elevated percentage of cells arrested in the G1/G0 phase of the cell cycle, enhanced beta-galactosidase activity, and a reduction in cell proliferation.
  • Additionally, these older cells showed increased gene expression of pro-inflammatory cytokines and miRNAs, significant markers of inflammation and cell aging.
  • The study also detected increased activity of apoptosis markers in these cells, indicating elevated levels of cell death with age.
  • Furthermore, the expression of genes involved in maintaining stem cell health and function, like those from the TET family and C-X-C chemokine receptor type 4 (CXCR4), decreased with age.
  • The researchers found that older ASCs had a higher IRE-1 activity, leading to increased endoplasmic reticulum stress, and reduced levels of glucose transporter 4 (GLUT-4) and the insulin receptor (INSR), compromising insulin sensitivity.

Implications

  • Overall, the findings imply that several molecular changes occur in ASCs derived from horses older than 5, and these changes significantly impair their regenerative potential.
  • The results of this study can be leveraged to identify potential drug targets that may help restore the regenerative capabilities of ASCs, thereby improving overall regenerative medicine practices in veterinary medicine.

Cite This Article

APA
Alicka M, Kornicka-Garbowska K, Kucharczyk K, Kępska M, Rӧcken M, Marycz K. (2020). Age-dependent impairment of adipose-derived stem cells isolated from horses. Stem Cell Res Ther, 11(1), 4. https://doi.org/10.1186/s13287-019-1512-6

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 4
PII: 4

Researcher Affiliations

Alicka, Michalina
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Kornicka-Garbowska, Katarzyna
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
  • International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114, Wisznia Mała, Poland.
Kucharczyk, Katarzyna
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Kępska, Martyna
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland.
Rӧcken, Michael
  • Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig University, 35392, Giessen, Germany.
Marycz, Krzysztof
  • Department of Experimental Biology, Wroclaw University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland. krzysztofmarycz@interia.pl.
  • International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114, Wisznia Mała, Poland. krzysztofmarycz@interia.pl.
  • Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig University, 35392, Giessen, Germany. krzysztofmarycz@interia.pl.

MeSH Terms

  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Adolescent
  • Adult
  • Age Factors
  • Animals
  • Child
  • Child, Preschool
  • Horses
  • Humans
  • Infant
  • Stem Cells / metabolism
  • Young Adult

Conflict of Interest Statement

The authors declare that they have no competing interests.

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