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BMC veterinary research2025; 21(1); 70; doi: 10.1186/s12917-024-04448-3

Comparison of the chondrogenic potential of eBMSCs and eUCMSCs in response to selected peptides and compounds.

Abstract: Cartilage injuries pose significant challenges in horses and often lead to post-traumatic osteoarthritis (PTOA). Despite the advances in surgical and regenerative techniques, the result in most cases is the formation of a fibrocartilage repair tissue. Cell-based cartilage therapies are mainly focused on equine bone marrow-derived mesenchymal stem cells (eBMSCs) as they are easily accessible, and multipotent. Nonetheless, alternative allogeneic sources, for example equine umbilical cord matrix mesenchymal stromal cells (eUCMSCs), hold promise given their non-invasive and readily accessible nature. Considerable research has been dedicated to exploring chondroinductive factors (e.g., peptides and small compounds), aiming to replace growth factors for inducing chondrogenesis. However, these factors have not yet translated to the equine community. Therefore, in the current study, we selected from the literature two promising peptides, CM10 and CK2.1, and two promising compounds, kartogenin and SM04690, and assessed their chondroinductive potential with both eBMSCs and eUCMSCs. In addition, the chondroinductive potential of eBMSCs was evaluated in monolayer and spheroid culture in both hypoxia and normoxia in response to dexamethasone and/or transforming growth factor beta 3 (TGF-β3). Results: Following 21 days of culture, none of the evaluated chondrogenic factors resulted in a higher gene expression of chondrogenic markers compared to the positive or negative controls with eBMSCs or eUCMSCs. Interestingly, spheroid culture in hypoxia with dexamethasone treatment (without TGF-β or any compound or peptide) was sufficient to induce the chondrogenic differentiation of eBMSCs. Conclusions: Based on cell response to the positive control, in the conditions employed in the current study, eBMSCs may be preferred over eUCMSCs for chondrogenesis. The current study supports the use of spheroid culture, and the use of dexamethasone over TGF-β or any of the compounds or peptides tested here from the prior literature to drive chondrogenesis with eBMSCs.
© 2025. The Author(s).
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Publication Date: 2025-02-17 PubMed ID: 39956895PubMed Central: PMC11831820DOI: 10.1186/s12917-024-04448-3Google Scholar: Lookup
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  • Journal Article
  • Comparative Study

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 article discusses a comparison of two types of substances’ potential to aid in the growth of cartilage using two types of stem cells derived primarily from horses. It also tests the effectiveness of culture condition variables. Despite trying various factors, none showed a notable increase in gene expression for cartilage markers compared to the control. However, they found that one type of cell culture (spheroid) under low oxygen with a specific treatment produced promising results.

Research Context

  • Cartilage injuries in horses often result in post-traumatic osteoarthritis (PTOA) – a significant challenge due to its difficulty in treatment. Despite technological advancements in surgeries and regenerative methods, most cases result in the formation of a fibrocartilage repair tissue.
  • Previous cell-based cartilage therapies focused primarily on equine bone marrow-derived mesenchymal stem cells (eBMSCs) because of their easy accessibility and multipotency. Still, alternative sources such as equine umbilical cord matrix mesenchymal stromal cells (eUCMSCs) are also promising because they can be accessed readily and non-invasively.
  • Many studies have been searching for chondroinductive factors such as peptides and small compounds that can replace growth factors for inducing chondrogenesis—a process that produces cartilage. However, this research has yet to yield practical results for the equine community.

Research Methods

  • In this research, two promising peptides, CM10 and CK2.1, and two promising compounds, kartogenin and SM04690, were selected based on the prior literature. These were then tested with both eBMSCs and eUCMSCs to assess their capability to help generate cartilage.
  • The research also evaluated the potential of eBMSCs to produce cartilage in a monolayer culture (single layer of cells) and a spheroid culture (three-dimensional model), under both low (hypoxia) and regular (normoxia) oxygen levels. Additionally, the team used a specific treatment (dexamethasone and/or transforming growth factor beta 3 (TGF-β3)) to evaluate the effectiveness of these culture factors.

Research Results

  • The study found that none of the tested substances resulted in a higher expression of genes associated with cartilage when compared to both positive and negative controls. This result applies to both eBMSCs and eUCMSCs, indicating that the selected peptides and compounds did not enhance cartilage generation.
  • However, the experiment found that spheroid culture under low oxygen conditions and treatment with dexamethasone—at the exclusion of TGF-β3 or any of the selected peptides or compounds—successfully induced chondrogenesis with eBMSCs.

Research Conclusions

  • From the results obtained in this study, it was concluded that under the given conditions, eBMSCs could potentially be more effective for chondrogenesis than eUCMSCs.
  • The research supports the use of spheroid culture and the implementation of dexamethasone rather than TGF-β3 or the tested peptides or compounds from the existing literature. This is for the purposes of promoting chondrogenesis with eBMSCs.

Cite This Article

APA
Ajeeb B, Kiyotake EA, Keefe PA, Phillips JN, Hatzel JN, Goodrich LR, Detamore MS. (2025). Comparison of the chondrogenic potential of eBMSCs and eUCMSCs in response to selected peptides and compounds. BMC Vet Res, 21(1), 70. https://doi.org/10.1186/s12917-024-04448-3

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 70
PII: 70

Researcher Affiliations

Ajeeb, Boushra
  • Stephenson School of Biomedical Engineering, University of Oklahoma, 101 David L Boren Blvd Norman, Norman, OK, 73019, USA.
Kiyotake, Emi A
  • Stephenson School of Biomedical Engineering, University of Oklahoma, 101 David L Boren Blvd Norman, Norman, OK, 73019, USA.
Keefe, Peggy A
  • Stephenson School of Biomedical Engineering, University of Oklahoma, 101 David L Boren Blvd Norman, Norman, OK, 73019, USA.
  • Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80521, USA.
Phillips, Jennifer Nikki
  • Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80521, USA.
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
Hatzel, Jennifer N
  • Department of Biomedical Sciences, Colorado State University, 3101 Rampart Road, Fort Collins, CO, 80521, USA.
Goodrich, Laurie R
  • Translational Medicine Institute, Colorado State University, 2350 Gillette Drive, Fort Collins, CO, 80521, USA.
  • Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA.
Detamore, Michael S
  • Stephenson School of Biomedical Engineering, University of Oklahoma, 101 David L Boren Blvd Norman, Norman, OK, 73019, USA. michael.detamore@colostate.edu.
  • Department of Biomedical Sciences, Colorado State University, 3101 Rampart Road, Fort Collins, CO, 80521, USA. michael.detamore@colostate.edu.

MeSH Terms

  • Animals
  • Horses
  • Chondrogenesis / drug effects
  • Mesenchymal Stem Cells / drug effects
  • Peptides / pharmacology
  • Dexamethasone / pharmacology
  • Umbilical Cord / cytology
  • Phthalic Acids / pharmacology
  • Cells, Cultured
  • Anilides / pharmacology
  • Transforming Growth Factor beta3 / pharmacology
  • Cell Differentiation / drug effects
  • Bone Marrow Cells / drug effects

Grant Funding

  • 21000647 / Oklahoma Center for Adult Stem Cell Research

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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Citations

This article has been cited 1 times.
  1. Shi L, Khan MZ, Ullah A, Liang H, Geng M, Akhtar MF, Na J, Han Y, Wang C. Advancements in Stem Cell Applications for Livestock Research: A Review. Vet Sci 2025 Apr 23;12(5).
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