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Frontiers in cell and developmental biology2023; 10; 1094124; doi: 10.3389/fcell.2022.1094124

The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations.

Abstract: The interfascicular matrix (IFM; also known as the endotenon) is critical to the mechanical adaptations and response to load in energy-storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT). We hypothesized that the IFM is a tendon progenitor cell niche housing an exclusive cell subpopulation. Immunolabelling of equine superficial digital flexor tendon was used to identify the interfascicular matrix niche, localising expression patterns of CD31 (endothelial cells), Desmin (smooth muscle cells and pericytes), CD146 (interfascicular matrix cells) and LAMA4 (interfascicular matrix basement membrane marker). Magnetic-activated cell sorting was employed to isolate and compare in vitro properties of CD146+ and CD146- subpopulations. Labelling for CD146 using standard histological and 3D imaging of large intact 3D segments revealed an exclusive interfascicular cell subpopulation that resides in proximity to a basal lamina which forms extensive, interconnected vascular networks. Isolated CD146+ cells exhibited limited mineralisation (osteogenesis) and lipid production (adipogenesis). This study demonstrates that the interfascicular matrix is a unique tendon cell niche, containing a vascular-rich network of basement membrane, CD31+ endothelial cells, Desmin+ mural cells, and CD146+ cell populations that are likely essential to tendon structure and/or function. Contrary to our hypothesis, interfascicular CD146+ subpopulations did not exhibit stem cell-like phenotypes. Instead, our results indicate CD146 as a pan-vascular marker within the tendon interfascicular matrix. Together with previous work demonstrating that endogenous tendon CD146+ cells migrate to sites of injury, our data suggest that their mobilisation to promote intrinsic repair involves changes in their relationships with local interfascicular matrix vascular and basement membrane constituents.
Publication Date: 2023-01-09 PubMed ID: 36699014PubMed Central: PMC9869387DOI: 10.3389/fcell.2022.1094124Google Scholar: Lookup
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  • Journal Article

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 investigated the role of the interfascicular matrix (IFM; also called the endotenon) within tendons, suggesting it contains a unique cell subpopulation that plays a critical part in the structure or function of tendons.

Study Objectives and Methods

  • The study aimed to demonstrate how the interfascicular matrix (IFM) in tendons plays a crucial role in the mechanical adaptations and response to load in energy-storing tendons such as human Achilles and equine superficial digital flexor tendons (SDFT). The researchers hypothesized that the IFM contains an exclusive tendon progenitor cell subpopulation.
  • The researchers used immunolabelling on horse superficial digital flexor tendons to identify the IFM niche and detect expression patterns of CD31, Desmin, CD146, and LAMA4. These are markers for endothelial cells, smooth muscle cells and pericytes, IFM cells, and IFM basement membrane, respectively.
  • The team isolated and examined properties of CD146+ and CD146- cell subpopulations through magnetic-activated cell sorting in vitro.

Results and Observations

  • The study found that CD146, in combination with standard histological and 3D imaging of intact 3D segments, highlighted a distinct cell subpopulation within the IFM that resides near a basal lamina. This lamina forms extensive, interconnected vascular networks.
  • The isolated CD146+ cells demonstrated limited osteogenesis (mineralisation) and adipogenesis (lipid production).

Conclusion

  • The research suggests that the interfascicular matrix in tendons acts as an exclusive cell niche. It contains a vascular-rich network comprised of CD31+ endothelial cells, Desmin+ mural cells, and CD146+ cell populations essential to tendon structure and/or function.
  • Contrary to the initial hypothesis, the researchers found that the CD146+ subpopulations within the IFM did not display stem cell-like characteristics. Instead, CD146 was identified as a general vascular marker within the tendon IFM.
  • Given that previous work has shown endogenous tendon CD146+ cells move towards injury sites, the researchers presented the idea that their mobilisation to promote repair might involve changes in their interactions with local IFM vascular and basement membrane structures.

Cite This Article

APA
Marr N, Zamboulis DE, Werling D, Felder AA, Dudhia J, Pitsillides AA, Thorpe CT. (2023). The tendon interfascicular basement membrane provides a vascular niche for CD146+ cell subpopulations. Front Cell Dev Biol, 10, 1094124. https://doi.org/10.3389/fcell.2022.1094124

Publication

ISSN: 2296-634X
NlmUniqueID: 101630250
Country: Switzerland
Language: English
Volume: 10
Pages: 1094124
PII: 1094124

Researcher Affiliations

Marr, Neil
  • Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.
Zamboulis, Danae E
  • Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.
Werling, Dirk
  • Pathobiology and Population Sciences, Centre for Vaccinology and Regenerative Medicine, Royal Veterinary College, Hatfield, United Kingdom.
Felder, Alessandro A
  • Research Software Development Group, Advanced Research Computing, University College London, London, United Kingdom.
Dudhia, Jayesh
  • Clinical Sciences and Services, Royal Veterinary College, Hatfield, United Kingdom.
Pitsillides, Andrew A
  • Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.
Thorpe, Chavaunne T
  • Comparative Biomedical Sciences, Royal Veterinary College, London, United Kingdom.

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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