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Frontiers in veterinary science2020; 7; 602403; doi: 10.3389/fvets.2020.602403

Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age.

Abstract: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10-100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients. To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs. study. BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups ( = 4, = 60); newborn (0 days), yearling (15-17 months), adult (5-8 years), middle-aged (12-18 years), and geriatric (≥22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers. The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types. Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated. The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of proliferation were observed in both MSC types from horses in the age groups below 18 years of age.
Copyright © 2020 Bagge, MacLeod and Berg.
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Publication Date: 2020-12-10 PubMed ID: 33363241PubMed Central: PMC7758322DOI: 10.3389/fvets.2020.602403Google Scholar: Lookup
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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 research article investigates the impact of donor age on the cellular proliferation of bone marrow and adipose tissue-derived mesenchyme stem cells from horses. The results indicate that the cell proliferation significantly declines when the donor age is advanced, highlighting challenges when using these types of cells for therapies in older patients.

Research Study and Methodology

  • The study was conducted to understand the effect of donor age on the proliferation of equine bone marrow (BM) and adipose tissue (AT) derived mesenchyme stem cells (MSCs). These cells are increasingly used to treat musculoskeletal and other injuries in horse practice.
  • Current treatment practices often require 10-100 million MSCs, which leads to the necessity of expanding primary cells in the culture before their therapeutic use.
  • Cell samples for the study were harvested from horses in five different age groups namely newborn (0 days), yearling (15 to 17 months), adult (5 to 8 years), middle-aged (12 to 18 years), and geriatric (22 years and above). Dermal fibroblasts were used as a biological control in this study.
  • A cell-proliferation test was conducted using an EdU incorporation assay, and steady-state mRNA levels were measured for targeted proliferation, aging, and senescence biomarkers.

Key Findings

  • The research demonstrated that the cellular proliferation of equine BM- and AT-derived MSCs significantly dropped in the geriatric cohort as compared to the younger age groups.
  • The study revealed that proliferation levels in both MSC types (BM and AT) were equally affected by the donor’s age.
  • Steady-state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from older horses. It also showed a down-regulation of some pro-cycling genes.

Implications of the Study

  • The study hints at potential challenges for the application of autologous cell-based therapies particularly in the older patient demographic, due to the observed decline in cell proliferation with increasing donor age.
  • While high levels of proliferation were observed in both MSC types from horses aged below 18, the aging associated decline in cell proliferation may influence the effectiveness of cell-therapeutic applications in older patients.

Study Limitations

  • This study did not look into any potential age-dependent differences in cell function parameters that would be pertinent to cell-therapy application.

Cite This Article

APA
Bagge J, MacLeod JN, Berg LC. (2020). Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age. Front Vet Sci, 7, 602403. https://doi.org/10.3389/fvets.2020.602403

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 7
Pages: 602403
PII: 602403

Researcher Affiliations

Bagge, Jasmin
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States.
MacLeod, James N
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY, United States.
Berg, Lise C
  • Department of Veterinary Clinical Sciences, University of Copenhagen, Copenhagen, Denmark.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Citations

This article has been cited 12 times.
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