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Connective tissue research2016; 57(6); 454-465; doi: 10.3109/03008207.2015.1117458

Tenogenesis of bone marrow-, adipose-, and tendon-derived stem cells in a dynamic bioreactor.

Abstract: Tendons are frequently damaged and fail to regenerate, leading to pain, loss of function, and reduced quality of life. Mesenchymal stem cells (MSCs) possess clinically useful tissue-regenerative properties and have been exploited for use in tendon tissue engineering and cell therapy. However, MSCs exhibit phenotypic heterogeneity based on the donor tissue used, and the efficacy of cell-based treatment modalities may be improved by optimizing cell source based on relative differentiation capacity. Equine MSCs were isolated from bone marrow (BM), adipose (AD), and tendon (TN), expanded in monolayer prior to seeding on decellularized tendon scaffolds (DTS), and cell-laden constructs were placed in a bioreactor designed to mimic the biophysical environment of the tendon. It was hypothesized that TN MSCs would differentiate toward a tendon cell phenotype better than BM and AD MSCs in response to a conditioning period involving cyclic mechanical stimulation for 1 hour per day at 3% strain and 0.33 Hz. All cell types integrated into DTS adopted an elongated morphology similar to tenocytes, expressed tendon marker genes, and improved tissue mechanical properties after 11 days. TN MSCs expressed the greatest levels of scleraxis, collagen type-I, and cartilage oligomeric matrix protein. Major histocompatibility class-II protein mRNA expression was not detected in any of the MSC types, suggesting low immunogenicity for allogeneic transplantation. The results suggest that TN MSCs are the ideal cell type for regenerative medicine therapies for tendinopathies, exhibiting the most mature tendon-like phenotype in vitro. When TN MSCs are unavailable, BM or AD MSCs may serve as robust alternatives.
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Publication Date: 2016-03-30 PubMed ID: 27028488DOI: 10.3109/03008207.2015.1117458Google 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 seeks to identify the most suitable source of mesenchymal stem cells (MSCs) for repairing damaged tendons, which typically struggle to regenerate on their own. Findings show that MSCs derived from tendon (TN MSCs) are the most effective in adopting tendon-like characteristics while adjusting to a biomechanical environment that simulates real tendon conditions.

Objective and Hypothesis

  • The important goal of the research was to establish the most effective mesenchymal stem cells (MSCs) for use in tendon regeneration. The research focused on MSCs derived from sources like bone marrow (BM), adipose (AD), and tendon (TN).
  • The guiding hypothesis was that the TN MSCs would best adapt to a tendon-like state compared to the BM and AD MSCs. This is examined under the assumption that the cells are subjected to cyclic mechanical stimulation for an hour every day, at a frequency of 0.33 Hz at a strain of 3%.

Methodology

  • The study made use of equine MSCs from the BM, AD, and TN areas. After enlarging these in a monolayer, they were placed on de-cellularized tendon scaffolds (DTS).
  • Arranging these cell-laden constructs in a special bioreactor, the researchers endeavored to imitate the biomechanical setting of a tendon.

Findings

  • All types of MSCs successfully integrated into the DTS and morphed into an extended shape similar to tenocytes, which are typical tendon cells.
  • These cells also expressed genes that mark the presence of tendons while enhancing the mechanical properties of the tissue after 11 days.
  • It was found that the MSCs derived from tendons (TN MSCs) demonstrated the highest levels of scleraxis, collagen type-I, and cartilage oligomeric matrix protein, all of which are crucial for tendon formation and structure.
  • No traces of Major histocompatibility class-II protein mRNA expression were found in any type of MSCs indicating low possibilities for immunogenicity in case of allogenic transplantation.
  • The results hinted at the fact that TN MSCs, based on their ability to mature into a tendon-like phenotype in vitro, could be the ideal choice for regenerative treatment procedures for tendinopathies.
  • In scenarios where TN MSCs are not available, the scientists have suggested that AD or BM MSCs could serve as viable alternatives.

Cite This Article

APA
Youngstrom DW, LaDow JE, Barrett JG. (2016). Tenogenesis of bone marrow-, adipose-, and tendon-derived stem cells in a dynamic bioreactor. Connect Tissue Res, 57(6), 454-465. https://doi.org/10.3109/03008207.2015.1117458

Publication

Connective tissue research
ISSN: 1607-8438
NlmUniqueID: 0365263
Country: England
Language: English
Volume: 57
Issue: 6
Pages: 454-465

Researcher Affiliations

Youngstrom, Daniel W
  • a Program in Biomedical and Veterinary Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.
LaDow, Jade E
  • a Program in Biomedical and Veterinary Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.
Barrett, Jennifer G
  • b Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center , Virginia Tech , Leesburg , VA , USA.

MeSH Terms

  • Adipose Tissue / cytology
  • Animals
  • Biomechanical Phenomena
  • Bioreactors
  • Bone Marrow Cells / cytology
  • Cattle
  • Cell Line
  • Collagen / metabolism
  • Colony-Forming Units Assay
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Glycosaminoglycans / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / metabolism
  • Horses
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Organogenesis
  • Tendons / cytology
  • Tissue Engineering / methods
  • Tissue Scaffolds

Citations

This article has been cited 36 times.
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