Mesenchymal Stromal Cells in Osteoarthritis: Evidence for Structural Benefit and Cartilage Repair

Song, Yujie; Jørgensen, Christian

doi:10.3390/biomedicines10061278

Cited by 18 publications

(16 citation statements)

References 80 publications

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“…In detail, EV-miRNAs had a preponderance towards protection for cartilage (ratio of 10.3), anti-inflammatory phenotype for macrophages (M2 vs. M1 ratio of 10.2) and anti-activation for T cells (ratio of 3.0). This is again consistent with the amelioration of cartilage structure and reduction in inflammation observed after MSCs or MSC-based products in OA patients [ 58 , 59 , 60 ]. In particular, two miRNAs tipped the balance towards healing capacity, hsa-miR-24-3p and hsa-miR-222-3p.…”

Section: Discussionsupporting

confidence: 84%

Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis

Ragni

Orfei

Girolamo

2022

Cells

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Bone-marrow-derived mesenchymal stromal cells (BMSCs) showed therapeutic potential in the treatment of musculoskeletal diseases, including osteoarthritis (OA). Their soluble mediators and extracellular vesicles (EVs), which make up the secretome, suppress immune response, attenuate inflammation and promote cartilage repair. EVs, as well as the whole secretome, have been investigated as cell free approaches for OA although, to date, a disease-tailored molecular fingerprint is missing. In this study, soluble mediators and miRNAs were sifted in the BMSCs’ secretome and EVs, respectively, and analyzed in the frame of cell types and factors involved in OA. The majority of identified molecules repress the activation of immune cells and the production of OA-related inflammatory mediators, as well as promote cartilage protection by acting on both chondrocytes homeostasis and extracellular matrix-degrading enzymes. These data provide the molecular ground for the therapeutic potential of BMSCs for regenerative applications for OA and support the use of secretome or EVs as cell-free applications in joint diseases.

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Section: Discussionsupporting

confidence: 84%

Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis

Ragni

Orfei

Girolamo

2022

Cells

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“…However, it is understood that progressive degradation and other aberrant changes in the joint tissues eventuate in an inflammation-mediated feedback loop that propagates the disease. Because of their ability to produce growth factors and anti-inflammatory cytokines that support tissue repair and regeneration, 31 MSCs are considered a promising biological therapy for mitigating OA. However, as MSCs can be derived from different tissue sources, it is of significant interest to determine if a specific MSC source illustrates heightened therapeutic potential for the treatment of OA.…”

Section: Discussionmentioning

confidence: 99%

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

et al. 2022

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Background: Clinical trials are currently underway to investigate the efficacy of intra-articular administration of mesenchymal stromal cells (MSCs) to mitigate osteoarthritis (OA) progression in the knee. Although multiple MSC sources exist, studies have yet to determine whether differences in therapeutic efficacy exist between them. Purpose: To compare the ability of intra-articularly injected adipose-derived MSCs (AD-MSCs) and amnion-derived MSCs (AM-MSCs) to mitigate the progression of knee OA in a small animal model of spontaneous OA, as well as to compare the therapeutic potential of MSCs in hyaluronic acid (HA) and in HA only with saline (OA) controls. Study Design: Controlled laboratory study. Methods: Injections of AD-MSCs or AM-MSCs suspended in HA or HA only were performed in the rear stifle joints of 3-month-old Dunkin Hartley guinea pigs (DHGPs). Repeat injections occurred at 2 and 4 months after the initial injection in each animal. Contralateral limbs received saline injections and served as untreated controls. Subsequently, joints were analyzed for osteoarthritic changes of the cartilage and subchondral bone via histologic and biochemical analyses. To evaluate MSC retention time in the joint space, DHGPs received a single intra-articular injection of fluorescently labeled AD-MSCs or AM-MSCs, and the fluorescence intensity was longitudinally tracked via an in vivo imaging system. Results: No statistically significant differences in outcomes were found when comparing the ability of AD-MSCs and AM-MSCs to mitigate OA. However, the injection of AD-MSCs, AM-MSCs, and HA-only treatments more effectively mitigated cartilage damage compared with that of saline controls by demonstrating higher amounts of cartilage glycosaminoglycan content and improved histological proteoglycan scoring while reducing the percentage of osteophytes present. Conclusion: Intra-articular injection of AD-MSCs, AM-MSCs, or HA only was able to similarly mitigate the progression of cartilage damage and reduce the percentage of osteophytes compared with that of saline controls in the DHGP. However, this study was unable to establish the superiority of AD-MSCs versus AM-MSCs as a treatment to mitigate spontaneous OA. Clinical Relevance: MSCs demonstrate the ability to mitigate the progression of knee OA and thus may be used in a prophylactic approach to delay the need for end-stage treatment strategies.

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“…(5). Research over the last few years has suggested that MSCs hold great potential for diverse therapeutic applications through putative immunomodulatory, anti-inflammatory effects or by stimulating tissue regeneration (6)(7)(8)(9).…”

Section: Mesenchymal Stromal Cell-based Therapiesmentioning

confidence: 99%

“…Regarding articular diseases, MSCs have shown the potency to reduce OA-related pain and increase cartilage repair (6,9). Additionally, OA-afflicted horses treated with intra-articular injections of MSCs show improvement in clinical signs, cartilage appearance and athletic performance (10)(11)(12).…”

Section: Mesenchymal Stromal Cell-based Therapiesmentioning

confidence: 99%

Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies

et al. 2023

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Osteoarthritis (OA) is a degenerative disease that eventually leads to the complete degradation of articular cartilage. Articular cartilage has limited intrinsic capacity for self-repair and, to date, there is no curative treatment for OA. Humans and horses have a similar articular cartilage and OA etiology. Thus, in the context of a One Health approach, progress in the treatment of equine OA can help improve horse health and can also constitute preclinical studies for human medicine. Furthermore, equine OA affects horse welfare and leads to significant financial losses in the equine industry. In the last few years, the immunomodulatory and cartilage regenerative potentials of mesenchymal stromal cells (MSCs) have been demonstrated, but have also raised several concerns. However, most of MSC therapeutic properties are contained in their secretome, particularly in their extracellular vesicles (EVs), a promising avenue for acellular therapy. From tissue origin to in vitro culture methods, various aspects must be taken into consideration to optimize MSC secretome potential for OA treatment. Immunomodulatory and regenerative properties of MSCs can also be enhanced by recreating a pro-inflammatory environment to mimic an in vivo pathological setting, but more unusual methods also deserve to be investigated. Altogether, these strategies hold substantial potential for the development of MSC secretome-based therapies suitable for OA management. The aim of this mini review is to survey the most recent advances on MSC secretome research with regard to equine OA.

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Mesenchymal Stromal Cells in Osteoarthritis: Evidence for Structural Benefit and Cartilage Repair

Cited by 18 publications

References 80 publications

Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis

Secreted Factors and Extracellular Vesicles Account for the Immunomodulatory and Tissue Regenerative Properties of Bone-Marrow-Derived Mesenchymal Stromal Cells for Osteoarthritis

Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

Equine osteoarthritis: Strategies to enhance mesenchymal stromal cell-based acellular therapies

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