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Cells2019; 8(10); doi: 10.3390/cells8101116

Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model.

Abstract: Osteoarthritis is a degenerative disease that strongly correlates with age and promotes the breakdown of joint cartilage and subchondral bone. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stromal cells (MSCs) isolated from adult tissues. It seems that MSCs derived from synovial joint tissues exhibit superior chondrogenic ability, but their unclear distribution and low frequency actually limit their clinical application. To date, the influence of aging on synovial joint derived MSCs' biological characteristics and differentiation abilities remains unknown, and a full understanding of the mechanisms involved in cellular aging is lacking. The aim of this study was therefore to investigate the presence of age-related alterations in synovial fluid MSCs and their influence on the potential ability of MSCs to differentiate toward chondrogenic phenotypes. Synovial fluid MSCs, isolated from healthy equine donors from 3 to 40 years old, were cultured in vitro and stimulated towards chondrogenic differentiation for up to 21 days. An equine model was chosen due to the high degree of similarity of the anatomy of the knee joint to the human knee joint and as spontaneous disorders develop that are clinically relevant to similar human disorders. The results showed a reduction in cell proliferation correlated with age and the presence of age-related tetraploid cells. Ultrastructural analysis demonstrated the presence of morphological features correlated with aging such as endoplasmic reticulum stress, autophagy, and mitophagy. Alcian blue assay and real-time PCR data showed a reduction of efficiency in the chondrogenic differentiation of aged synovial fluid MSCs compared to young MSCs. All these data highlighted the influence of aging on MSCs' characteristics and ability to differentiate towards chondrogenic differentiation and emphasize the importance of considering age-related alterations of MSCs in clinical applications.
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Publication Date: 2019-09-20 PubMed ID: 31547126PubMed Central: PMC6829538DOI: 10.3390/cells8101116Google 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 focuses on the effects of aging on mesenchymal stromal cells (MSCs) in the synovial joint fluid, and how these cells’ potential to transform into cartilage cells gets altered by age, using an equine model.

Objectives and Background

  • The main intent of this research is to understand the changes that aging brings in the mesenchymal stromal cells (MSCs) from the synovial fluid in the joints and how these alterations influence their ability to change into chondrogenic (cartilage) cells.
  • The interest in understanding this comes from an increased focus on developing therapies using adult tissue-derived MSCs as they are believed to have superior chondrogenic abilities. This could potentially help in healing osteoarthritis, which is a degenerative disease that causes the breakdown of joint cartilage and subchondral bone.

Methodology

  • The study revolves around synovial fluid MSCs obtained from healthy horses of varying ages (3-40 years). These MSCs were cultured in a lab setting and stimulated towards chondrogenic differentiation for a span of 21 days.
  • An equine model was chosen for this study because of the similarities it shares with the human knee joint anatomy, and the spontaneous disorders it develops that are clinically relevant to human disorders.

Findings

  • The researchers found that as the age increased, cell proliferation decreased. They also noticed the presence of tetraploid cells, which are cells having twice the usual number of chromosomes, a phenomenon often associated with aging.
  • Ultrastructural analysis of these cells revealed features associated with aging like heightened stress in endoplasmic reticulum (part of the cell dealing with protein synthesis and lipid metabolism), autophagy (self-eating of cells to replace worn-out parts), and mitophagy (type of autophagy where mitochondria is specifically targeted).
  • Evidences drawn from Alcian blue assay (a test to assess the presence of cartilage) and real-time PCR data indicated a reduction in the effectiveness of aged synovial fluid MSCs to differentiate into cartilage cells compared to young MSCs.

Impact and Conclusions

  • The research highlighted the effect of aging on the characteristics of MSCs and their ability to differentiate into chondrogenic cells. This raises an important point to be considered when evaluating the effectiveness of cell-based therapies for degenerative diseases like osteoarthritis, as the age-related alterations of MSCs might affect the outcome.

Cite This Article

APA
Mazzotti E, Teti G, Falconi M, Chiarini F, Barboni B, Mazzotti A, Muttini A. (2019). Age-Related Alterations Affecting the Chondrogenic Differentiation of Synovial Fluid Mesenchymal Stromal Cells in an Equine Model. Cells, 8(10). https://doi.org/10.3390/cells8101116

Publication

Cells
ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 8
Issue: 10

Researcher Affiliations

Mazzotti, Eleonora
  • Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy. elemazzo90@icloud.com.
Teti, Gabriella
  • Department of Biomedical and Neuromotor Sciences, University di Bologna, 40126 Bologna, Italy. gabriella.teti2@unibo.it.
Falconi, Mirella
  • Department of Biomedical and Neuromotor Sciences, University di Bologna, 40126 Bologna, Italy. mirella.falconi@unibo.it.
Chiarini, Francesca
  • CNR-National Research Council of Italy, Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza", Unit of Bologna, 40136 Bologna, Italy. francesca.chiarini@cnr.it.
  • IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy. francesca.chiarini@cnr.it.
Barboni, Barbara
  • Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy. bbarboni@unite.it.
Mazzotti, Antonio
  • st Orthopedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, Via Giulio Cesare Pupilli 1, 40136 Bologna, Italy. antonio.mazzotti@ior.it.
Muttini, Aurelio
  • Faculty of Bioscience and Agro-Food and Environmental Technology, University of Teramo, 64100 Teramo, Italy. amuttini@unite.it.
  • Stem TeCh Group, 66100 Chieti, Italy. amuttini@unite.it.

MeSH Terms

  • Aging / pathology
  • Aging / physiology
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Senescence / physiology
  • Chondrocytes / pathology
  • Chondrocytes / physiology
  • Chondrogenesis / physiology
  • Disease Models, Animal
  • Female
  • Horses
  • Humans
  • Male
  • Mesenchymal Stem Cells / pathology
  • Mesenchymal Stem Cells / physiology
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology
  • Synovial Fluid / cytology

Conflict of Interest Statement

The authors declare no conflict of interest.

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