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Stem cell research & therapy2020; 11(1); 184; doi: 10.1186/s13287-020-01692-w

Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes.

Abstract: Tendon injuries occur frequently in human and equine athletes. Treatment options are limited, and the prognosis is often poor with functionally deficient scar tissue resulting. Fetal tendon injuries in contrast are capable of healing without forming scar tissue. Embryonic stem cells (ESCs) may provide a potential cellular therapeutic to improve adult tendon regeneration; however, whether they can mimic the properties of fetal tenocytes is unknown. To this end, understanding the unique expression profile of normal adult and fetal tenocytes is crucial to allow validation of ESC-derived tenocytes as a cellular therapeutic. Equine adult, fetal and ESC-derived tenocytes were cultured in a three-dimensional environment, with histological, morphological and transcriptomic differences compared. Additionally, the effects on gene expression of culturing adult and fetal tenocytes in either conventional two-dimensional monolayer culture or three-dimensional culture were compared using RNA sequencing. No qualitative differences in three-dimensional tendon constructs generated from adult, fetal and ESCs were found using histological and morphological analysis. However, genome-wide transcriptomic analysis using RNA sequencing revealed that ESC-derived tenocytes' transcriptomic profile more closely resembled fetal tenocytes as opposed to adult tenocytes. Furthermore, this study adds to the growing evidence that monolayer cultured cells' gene expression profiles converge, with adult and fetal tenocytes having only 10 significantly different genes when cultured in this manner. In contrast, when adult and fetal tenocytes were cultured in 3D, large distinctions in gene expression between these two developmental stages were found, with 542 genes being differentially expressed. The information provided in this study makes a significant contribution to the investigation into the differences between adult reparative and fetal regenerative cells and supports the concept of using ESC-derived tenocytes as a cellular therapy. Comparing two- and three-dimensional culture also indicates three-dimensional culture as being a more physiologically relevant culture system for determining transcriptomic difference between the same cell types from different developmental stages.
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Publication Date: 2020-05-19 PubMed ID: 32430075PubMed Central: PMC7238619DOI: 10.1186/s13287-020-01692-wGoogle 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.

The research study demonstrates that embryonic stem cells (ESCs) can mimic the properties of fetal tendon cells (tenocytes) rather than adult tenocytes — an insight that may inform future strategies for improving tendon repair in adult humans and horses.

Understanding the Study

The study centers on two key problems encountered in the treatment of tendon injuries:

  • Despite current treatments, such injuries usually heal poorly, often resulting in the formation of deficient scar tissue that affects functionality.
  • In stark contrast, fetal tendon injuries can heal without scar tissue formation, suggesting a potential role for ESCs in improving adult tendon regeneration.

Methodology

The research was focused on examining the similarities and differences between normal adult, fetal, and ESC-derived tenocytes:

  • These three variants of tenocytes were cultured in a three-dimensional environment.
  • Different aspects such as histological, morphological, and transcriptomic were compared among the tenocytes.
  • Study also included comparison of gene expression effects in adult and fetal tenocytes cultured in two different ways: traditional two-dimensional monolayer culture and three-dimensional culture.

Findings

Key findings of this research centered around the properties of ESC-derived tenocytes and the differences in gene expression profiles of adult versus fetal tenocytes in different culture environments:

  • A significant discovery here is that ESC-derived tenocytes’ transcriptomic profile resembled more with fetal tenocytes than adult tenocytes.
  • No noteworthy differences were found in the tendon constructs created using adult, fetal and ESCs in terms of histological and morphological analysis.
  • In two-dimensional cell culture, both adult and fetal tenocytes had similar gene expression profiles, differing only in 10 genes.
  • However, in three-dimensional culture, there were significant gene expression differences between adult and fetal tenocytes, with 542 genes being differentially expressed.

Significance of the Study

This research contributes to the broader understanding of cellular differences between adult and fetal tendon cells and supports the idea of using ESC-derived tenocytes as a potential cellular therapy for tendon injuries. The comparison between two- and three-dimensional culture methods also suggests that three-dimensional culture is more physiologically relevant for detecting transcriptomic differences between the same cell types from different stages of development.

Cite This Article

APA
Paterson YZ, Cribbs A, Espenel M, Smith EJ, Henson FMD, Guest DJ. (2020). Genome-wide transcriptome analysis reveals equine embryonic stem cell-derived tenocytes resemble fetal, not adult tenocytes. Stem Cell Res Ther, 11(1), 184. https://doi.org/10.1186/s13287-020-01692-w

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 184
PII: 184

Researcher Affiliations

Paterson, Y Z
  • Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK. yzp20@cam.ac.uk.
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK. yzp20@cam.ac.uk.
Cribbs, A
  • Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.
Espenel, M
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.
Smith, E J
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.
Henson, F M D
  • Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge, CB3 0ES, UK.
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.
Guest, D J
  • Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK.

MeSH Terms

  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Embryonic Stem Cells
  • Gene Expression Profiling
  • Horses
  • Humans
  • Tendons
  • Tenocytes

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
  1. Smith EJ, Beaumont RE, McClellan A, Sze C, Palomino Lago E, Hazelgrove L, Dudhia J, Smith RKW, Guest DJ. Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors.. Cell Tissue Res 2023 Mar;391(3):523-544.
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  2. Oreff GL, Fenu M, Vogl C, Ribitsch I, Jenner F. Species variations in tenocytes' response to inflammation require careful selection of animal models for tendon research.. Sci Rep 2021 Jun 14;11(1):12451.
    doi: 10.1038/s41598-021-91914-9pubmed: 34127759google scholar: lookup
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