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International journal of molecular sciences2018; 19(9); doi: 10.3390/ijms19092549

Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment.

Abstract: Transplantation of multipotent mesenchymal progenitor cells is a valuable option for treating tendon disease. Tenogenic differentiation leading to cell replacement and subsequent matrix modulation may contribute to the regenerative effects of these cells, but it is unclear whether this occurs in the inflammatory environment of acute tendon disease. Equine adipose-derived stromal cells (ASC) were cultured as monolayers or on decellularized tendon scaffolds in static or dynamic conditions, the latter represented by cyclic stretching. The impact of different inflammatory conditions, as represented by supplementation with interleukin-1β and/or tumor necrosis factor-α or by co-culture with allogeneic peripheral blood leukocytes, on ASC functional properties was investigated. High cytokine concentrations increased ASC proliferation and osteogenic differentiation, but decreased chondrogenic differentiation and ASC viability in scaffold culture, as well as tendon scaffold repopulation, and strongly influenced musculoskeletal gene expression. Effects regarding the latter differed between the monolayer and scaffold cultures. Leukocytes rather decreased ASC proliferation, but had similar effects on viability and musculoskeletal gene expression. This included decreased expression of the tenogenic transcription factor scleraxis by an inflammatory environment throughout culture conditions. The data demonstrate that ASC tenogenic properties are compromised in an inflammatory environment, with relevance to their possible mechanisms of action in acute tendon disease.
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Publication Date: 2018-08-28 PubMed ID: 30154348PubMed Central: PMC6163784DOI: 10.3390/ijms19092549Google 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.

The research indicates that the potential for multipotent mesenchymal progenitor cells to regenerate tendon tissue may be compromised when exposed to inflammation, as is found in cases of acute tendon disease. This finding questions the efficacy of these cells in treating tendon disease in such conditions.

Study Overview

  • The primary aim of the study was to assess how the potential of multipotent mesenchymal progenitor cells (specifically, adipose-derived stromal cells or ASC) for tendon regeneration (tenogenesis) is impacted under conditions of inflammation.
  • The ASC were cultured in different environments – as monolayers or on decellularized tendon scaffolds, under either static conditions or conditions of cyclic stretching that mimic the dynamic environment within the body’s tissues.
  • The inflammatory conditions were represented either by supplements of interleukin-1β and/or tumor necrosis factor-α, or by co-culturing with allogeneic peripheral blood leukocytes (white blood cells of a different individual of the same species).

Findings

  • High concentrations of the inflammation-associated cytokines led to an increase in the proliferation and osteogenic (bone-tissue related) differentiation of the ASC, but decreased their chondrogenic (cartilage-tissue related) differentiation and viability in the scaffold culture.
  • Also, the repopulation of the tendon scaffold by ASC and the expression of specific musculoskeletal genes by the ASC was negatively affected by the high cytokine levels. The effects on gene expression varied between the monolayer and scaffold cultures.
  • Co-culture with leukocytes similarly led to decreased ASC proliferation and viability, and influenced musculoskeletal gene expression, including a decrease in the expression of the tenogenic transcription factor scleraxis.
  • Overall, these findings indicated that the tenogenic properties of the ASC were compromised in an inflammatory environment, suggesting that potential regenerative effects of these cells may be limited in cases of acute tendon disease where inflammation is present.

Relevance

  • This study sheds important light on the potential limitations of ASC transplantation for tendon disease treatment, as the regenerative effects of these cells may be compromised under the inflammatory conditions often present in acute instances of the disease.
  • It suggests that approaches for controlling inflammation may need to be considered in conjunction with cell transplantation therapies for the treatment of tendon disease.

Cite This Article

APA
Brandt L, Schubert S, Scheibe P, Brehm W, Franzen J, Gross C, Burk J. (2018). Tenogenic Properties of Mesenchymal Progenitor Cells Are Compromised in an Inflammatory Environment. Int J Mol Sci, 19(9). https://doi.org/10.3390/ijms19092549

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 19
Issue: 9

Researcher Affiliations

Brandt, Luisa
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. luisa.brandt@sikt.uni-leipzig.de.
Schubert, Susanna
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. susanna.schubert@sikt.uni-leipzig.de.
  • Institute of Veterinary Physiology, University of Leipzig, 04103 Leipzig, Germany. susanna.schubert@sikt.uni-leipzig.de.
Scheibe, Patrick
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. patrick.scheibe@sikt.uni-leipzig.de.
Brehm, Walter
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. brehm@vetmed.uni-leipzig.de.
  • Department for Horses, Veterinary Teaching Hospital, University of Leipzig, 04103 Leipzig, Germany. brehm@vetmed.uni-leipzig.de.
Franzen, Jan
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. jan.franzen96@gmx.de.
  • Institute of Veterinary Physiology, University of Leipzig, 04103 Leipzig, Germany. jan.franzen96@gmx.de.
Gross, Claudia
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. claudia_gross1@gmx.de.
Burk, Janina
  • Saxon Incubator for Clinical Translation (SIKT), University of Leipzig, 04103 Leipzig, Germany. burk@rz.uni-leipzig.de.
  • Institute of Veterinary Physiology, University of Leipzig, 04103 Leipzig, Germany. burk@rz.uni-leipzig.de.
  • Institute of Biotechnology, University of Natural Resources and Life Sciences (BOKU), 1190 Vienna, Austria. burk@rz.uni-leipzig.de.

MeSH Terms

  • Adipogenesis
  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Cellular Microenvironment
  • Chondrogenesis
  • Coculture Techniques
  • Cytokines / metabolism
  • Extracellular Matrix / metabolism
  • Horses
  • Humans
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Tendons
  • Tissue Scaffolds

Grant Funding

  • BU3110/1-1 / Deutsche Forschungsgemeinschaft

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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