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Plasticity Comparison of Two Stem Cell Sources with Different Hox Gene Expression Profiles in Response to Cobalt Chloride Treatment during Chondrogenic Differentiation
by
, , , , and
Sahar Khajeh
1,†,
Vahid Razban
2,3,†,
Yasaman Naeimzadeh
2,
Elham Nadimi
2,
Reza Asadi-Golshan
4,
Zahra Heidari
2,
Tahereh Talaei-Khozani
5,6,
Farzaneh Dehghani
6,7,
Zohreh Mostafavi-Pour
8,9 and
Masoud Shirali
10,11,*
1
Bone and Joint Diseases Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
2
Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
3
Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
4
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran 14166-34793, Iran
5
Tissue Engineering Laboratory, Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
6
Department of Anatomy, School of Medicine, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
7
Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
8
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
9
Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
10
School of Biological Sciences, Queen’s University Belfast, Belfast BT9 5AJ, UK
11
Agri-Food and Biosciences Institute, Hillsborough BT26 6DR, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Biology 2024, 13(8), 560; https://doi.org/10.3390/biology13080560
Submission received: 17 June 2024
/
Revised: 20 July 2024
/
Accepted: 22 July 2024
/
Published: 24 July 2024
(This article belongs to the Special Issue Mesenchymal Stem Cells: What We Have Learned and How to Manage Them)
Simple Summary
When joints are harmed due to injury, inheritance, or aging, it is difficult for the body to heal damaged cartilage. This is a major cause of pain and disability worldwide. With increasing life expectancy, millions of adults are affected, and enormous costs are imposed on health care systems. Scientists are attempting to use stem cells to create new cartilage-like tissue as a potential solution. However, the most suitable stem cell type for cartilage repair has not been defined. This study compared the ability to generate cartilage-like tissue by using two stem cell types that were derived from human bone marrow and dental pulp. To produce cartilage, the tissue’s environment should be simulated for stem cells in a laboratory. Therefore, the low-oxygen tension of joint cartilage was simulated using a simple and inexpensive chemical, cobalt chloride. The results showed that dental pulp stem cells could produce higher quality tissue that closely resembled human joint cartilage in terms of its structure and organization that could form the primary base of normal function. While further research is necessary, these initial findings represent a promising step toward using stem cells more beneficially to enhance a patient’s quality of life.
Abstract
The limited self-repair capacity of articular cartilage is a challenge for healing injuries. While mesenchymal stem/stromal cells (MSCs) are a promising approach for tissue regeneration, the criteria for selecting a suitable cell source remain undefined. To propose a molecular criterion, dental pulp stem cells (DPSCs) with a Hox-negative expression pattern and bone marrow mesenchymal stromal cells (BMSCs), which actively express Hox genes, were differentiated towards chondrocytes in 3D pellets, employing a two-step protocol. The MSCs’ response to preconditioning by cobalt chloride (CoCl2), a hypoxia-mimicking agent, was explored in an assessment of the chondrogenic differentiation’s efficiency using morphological, histochemical, immunohistochemical, and biochemical experiments. The preconditioned DPSC pellets exhibited significantly elevated levels of collagen II and glycosaminoglycans (GAGs) and reduced levels of the hypertrophic marker collagen X. No significant effect on GAGs production was observed in the preconditioned BMSC pellets, but collagen II and collagen X levels were elevated. While preconditioning did not modify the ALP specific activity in either cell type, it was notably lower in the DPSCs differentiated pellets compared to their BMSCs counterparts. These results could be interpreted as demonstrating the higher plasticity of DPSCs compared to BMSCs, suggesting the contribution of their unique molecular characteristics, including their negative Hox expression pattern, to promote a chondrogenic differentiation potential. Consequently, DPSCs could be considered compelling candidates for future cartilage cell therapy.
