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Are mesenchymal stem cells in rheumatoid arthritis the good or bad guys?

De Bari C - Arthritis Res. Ther. (2015)

Bottom Line: An important question to address relates to the relationship between MSCs and FLSs.MSCs and FLSs could be the same cell type with functional specialisation or represent different functional stages of the same stromal lineage.It will also examine the immunomodulatory properties of the MSCs and the potential to harness such properties for the treatment of RA.

View Article: PubMed Central - PubMed

Affiliation: Regenerative Medicine Group, Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. c.debari@abdn.ac.uk.

ABSTRACT
The advancements in our understanding of the inflammatory and immune mechanisms in rheumatoid arthritis (RA) have fuelled the development of targeted therapies that block cytokine networks and pathogenic immune cells, leading to a considerable improvement in the management of RA patients. Nonetheless, no therapy is curative and clinical remission does not necessarily correspond to non-progression of joint damage. Hence, the biomedical community has redirected scientific efforts and resources towards the investigation of other biological aspects of the disease, including the mechanisms driving tissue remodelling and repair. In this regard, stem cell research has attracted extraordinary attention, with the ultimate goal to develop interventions for the biological repair of damaged tissues in joint disorders, including RA. The recent evidence that mesenchymal stem cells (MSCs) with the ability to differentiate into cartilage are present in joint tissues raises an opportunity for therapeutic interventions via targeting intrinsic repair mechanisms. Under physiological conditions, MSCs in the joint are believed to contribute to the maintenance and repair of joint tissues. In RA, however, the repair function of MSCs appears to be repressed by the inflammatory milieu. In addition to being passive targets, MSCs could interact with the immune system and play an active role in the perpetuation of arthritis and progression of joint damage. Like MSCs, fibroblast-like synoviocytes (FLSs) are part of the stroma of the synovial membrane. During RA, FLSs undergo proliferation and contribute to the formation of the deleterious pannus, which mediates damage to articular cartilage and bone. Both FLSs and MSCs are contained within the mononuclear cell fraction in vitro, from which they can be culture expanded as plastic-adherent fibroblast-like cells. An important question to address relates to the relationship between MSCs and FLSs. MSCs and FLSs could be the same cell type with functional specialisation or represent different functional stages of the same stromal lineage. This review will discuss the roles of MSCs in RA and will address current knowledge of the relative identity between MSCs and FLSs. It will also examine the immunomodulatory properties of the MSCs and the potential to harness such properties for the treatment of RA.

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Related in: MedlinePlus

Possible effects of mesenchymal stem cells (MSCs) on regulatory T cell (Treg) and Th17 cell populations in rheumatoid arthritis (RA). CIA, collagen-induced arthritis; IFNγ, interferon-γ; IL-2, interleukin-2; MHC-I, class I major histocompatibility complex; RORγt, retinoic acid receptor-related orphan receptor γt; TGFβ, transforming growth factor β; TNFα, tumour necrosis factor α. Adapted from MacDonald et al., Arthritis Rheum 2011 [40].
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Fig2: Possible effects of mesenchymal stem cells (MSCs) on regulatory T cell (Treg) and Th17 cell populations in rheumatoid arthritis (RA). CIA, collagen-induced arthritis; IFNγ, interferon-γ; IL-2, interleukin-2; MHC-I, class I major histocompatibility complex; RORγt, retinoic acid receptor-related orphan receptor γt; TGFβ, transforming growth factor β; TNFα, tumour necrosis factor α. Adapted from MacDonald et al., Arthritis Rheum 2011 [40].

Mentions: The immunosuppressive and anti-inflammatory properties of cultured MSCs have led to these cells being tested for their therapeutic potential in preclinical models of RA-like inflammatory arthritis (reviewed in [40]). Several studies suggested that bone marrow- or adipose-derived MSCs have the ability to 'reset' the immune system by reducing the deleterious Th1/Th17 response and enhancing the protective regulatory T cell response (Figure 2), although other studies failed to demonstrate improvement with MSC treatment [40]. The inconsistent results in preclinical models may be due to several variables such as source of MSCs (murine syngeneic or allogeneic, or human), tissue of origin of MSCs, timing of treatment, number of cells injected, route of injection and treatment regimes, different culture conditions, as well as differences in mouse strains and animal housing conditions.Figure 2


Are mesenchymal stem cells in rheumatoid arthritis the good or bad guys?

De Bari C - Arthritis Res. Ther. (2015)

Possible effects of mesenchymal stem cells (MSCs) on regulatory T cell (Treg) and Th17 cell populations in rheumatoid arthritis (RA). CIA, collagen-induced arthritis; IFNγ, interferon-γ; IL-2, interleukin-2; MHC-I, class I major histocompatibility complex; RORγt, retinoic acid receptor-related orphan receptor γt; TGFβ, transforming growth factor β; TNFα, tumour necrosis factor α. Adapted from MacDonald et al., Arthritis Rheum 2011 [40].
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4416346&req=5

Fig2: Possible effects of mesenchymal stem cells (MSCs) on regulatory T cell (Treg) and Th17 cell populations in rheumatoid arthritis (RA). CIA, collagen-induced arthritis; IFNγ, interferon-γ; IL-2, interleukin-2; MHC-I, class I major histocompatibility complex; RORγt, retinoic acid receptor-related orphan receptor γt; TGFβ, transforming growth factor β; TNFα, tumour necrosis factor α. Adapted from MacDonald et al., Arthritis Rheum 2011 [40].
Mentions: The immunosuppressive and anti-inflammatory properties of cultured MSCs have led to these cells being tested for their therapeutic potential in preclinical models of RA-like inflammatory arthritis (reviewed in [40]). Several studies suggested that bone marrow- or adipose-derived MSCs have the ability to 'reset' the immune system by reducing the deleterious Th1/Th17 response and enhancing the protective regulatory T cell response (Figure 2), although other studies failed to demonstrate improvement with MSC treatment [40]. The inconsistent results in preclinical models may be due to several variables such as source of MSCs (murine syngeneic or allogeneic, or human), tissue of origin of MSCs, timing of treatment, number of cells injected, route of injection and treatment regimes, different culture conditions, as well as differences in mouse strains and animal housing conditions.Figure 2

Bottom Line: An important question to address relates to the relationship between MSCs and FLSs.MSCs and FLSs could be the same cell type with functional specialisation or represent different functional stages of the same stromal lineage.It will also examine the immunomodulatory properties of the MSCs and the potential to harness such properties for the treatment of RA.

View Article: PubMed Central - PubMed

Affiliation: Regenerative Medicine Group, Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK. c.debari@abdn.ac.uk.

ABSTRACT
The advancements in our understanding of the inflammatory and immune mechanisms in rheumatoid arthritis (RA) have fuelled the development of targeted therapies that block cytokine networks and pathogenic immune cells, leading to a considerable improvement in the management of RA patients. Nonetheless, no therapy is curative and clinical remission does not necessarily correspond to non-progression of joint damage. Hence, the biomedical community has redirected scientific efforts and resources towards the investigation of other biological aspects of the disease, including the mechanisms driving tissue remodelling and repair. In this regard, stem cell research has attracted extraordinary attention, with the ultimate goal to develop interventions for the biological repair of damaged tissues in joint disorders, including RA. The recent evidence that mesenchymal stem cells (MSCs) with the ability to differentiate into cartilage are present in joint tissues raises an opportunity for therapeutic interventions via targeting intrinsic repair mechanisms. Under physiological conditions, MSCs in the joint are believed to contribute to the maintenance and repair of joint tissues. In RA, however, the repair function of MSCs appears to be repressed by the inflammatory milieu. In addition to being passive targets, MSCs could interact with the immune system and play an active role in the perpetuation of arthritis and progression of joint damage. Like MSCs, fibroblast-like synoviocytes (FLSs) are part of the stroma of the synovial membrane. During RA, FLSs undergo proliferation and contribute to the formation of the deleterious pannus, which mediates damage to articular cartilage and bone. Both FLSs and MSCs are contained within the mononuclear cell fraction in vitro, from which they can be culture expanded as plastic-adherent fibroblast-like cells. An important question to address relates to the relationship between MSCs and FLSs. MSCs and FLSs could be the same cell type with functional specialisation or represent different functional stages of the same stromal lineage. This review will discuss the roles of MSCs in RA and will address current knowledge of the relative identity between MSCs and FLSs. It will also examine the immunomodulatory properties of the MSCs and the potential to harness such properties for the treatment of RA.

Show MeSH
Related in: MedlinePlus