“…In the other side, only TLR4 ligand (LPS) increased the expression of CD86. Interestingly, the expression of CD74 (HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain) and CD105 was not modulated by TLR activation (6667). …”
Section: Msc Phenotype and Tlr-primingmentioning
confidence: 99%
“…Moreover, under TLR3 stimulation, mesenchymal stromal cells from human tonsils (T-MSCs) acquire a chemoattractant profile that is suitable for allowing immune cells to migrate into MSCs surrounding environment. Indeed, TLR3 activation increased in the secretion of many chemokine such as CXCL5, CXCL6, CXCL1, CXCL8, and CXCL10 (67). In terms of leukocyte binding, BM-MSCs responded differently to TLR3 and TLR4 activation (63).…”
Section: Msc Immunomodulation and Tlr-primingmentioning
Mesenchymal Stromal Cells (MSCs) are potential cellular candidates for several immunotherapy purposes. Their multilineage potential and immunomodulatory properties make them interesting tools for the treatment of various immunological diseases. However, depending on the local microenvironment, diverse biological functions of MSCs can be modulated. Indeed, during infections such as obtained following TLR-agonist engagement (called as TLR priming), the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs can present critical changes, which could further affect their therapeutic potential. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects in particular during infectious episodes and to find the suitable experimental settings to study that. Pre-stimulation of MSCs with a specific TLR ligand may serve as an effective priming step to modulate one of its function to achieve a desired therapeutic issue.
“…In the other side, only TLR4 ligand (LPS) increased the expression of CD86. Interestingly, the expression of CD74 (HLA class II histocompatibility antigen gamma chain also known as HLA-DR antigens-associated invariant chain) and CD105 was not modulated by TLR activation (6667). …”
Section: Msc Phenotype and Tlr-primingmentioning
confidence: 99%
“…Moreover, under TLR3 stimulation, mesenchymal stromal cells from human tonsils (T-MSCs) acquire a chemoattractant profile that is suitable for allowing immune cells to migrate into MSCs surrounding environment. Indeed, TLR3 activation increased in the secretion of many chemokine such as CXCL5, CXCL6, CXCL1, CXCL8, and CXCL10 (67). In terms of leukocyte binding, BM-MSCs responded differently to TLR3 and TLR4 activation (63).…”
Section: Msc Immunomodulation and Tlr-primingmentioning
Mesenchymal Stromal Cells (MSCs) are potential cellular candidates for several immunotherapy purposes. Their multilineage potential and immunomodulatory properties make them interesting tools for the treatment of various immunological diseases. However, depending on the local microenvironment, diverse biological functions of MSCs can be modulated. Indeed, during infections such as obtained following TLR-agonist engagement (called as TLR priming), the phenotype, multilineage potential, hematopoietic support and immunomodulatory capacity of MSCs can present critical changes, which could further affect their therapeutic potential. Thus, for appropriate clinical application of MSCs, it is important to well know and understand these effects in particular during infectious episodes and to find the suitable experimental settings to study that. Pre-stimulation of MSCs with a specific TLR ligand may serve as an effective priming step to modulate one of its function to achieve a desired therapeutic issue.
“…The characteristics and potential of MSCs to be used for cell banking have been previously reported (8). The therapeutic potential of T-MSCs in the treatment of liver (9,10), pancreas (11), parathyroid gland (12), skeletal muscle (13), and bone (14) diseases, as well as the mechanisms that underlie their immunomodulatory effects (15)(16)(17)(18), have been described previously.…”
Mesenchymal stem cells (MSCs) are often considered to be a good source for the development of regenerative medicine. Previously, we reported that tonsil‑derived MSC conditioned medium (T‑MSC CM) produces visceral fat reducing effects. As reduced visceral adiposity is closely associated with an increase in circulating adiponectin, the present study investigated the effects of T‑MSC CM on adiponectin production. T‑MSC CM was collected from previously isolated and characterized T‑MSCs and injected into senescence‑accelerated mouse prone 6 mice, which exhibit characteristics of aging and obesity. The results demonstrated a reduction in mouse weight and epididymal adipose tissue (eAT) mass following injection of T‑MSC CM. Significant increases in adiponectin expression in the eAT, and total and high molecular weight (HMW) adiponectin in the circulation were observed in the T‑MSC CM‑injected mice compared with control mice using reverse transcription‑quantitative polymerase chain reaction, western blot analysis and ELISA. In 3T3‑L1 adipocytes, T‑MSC CM treatment increased adiponectin secretion and multimerization, as detected using western blotting under non‑reducing and non‑heat‑denaturing conditions. Furthermore, glucose oxidase was used to induce oxidative stress in 3T3‑L1 adipocytes and it was observed that T‑MSC CM reduced reactive oxygen species production and the expression of certain oxidative stress markers. In addition, the results also demonstrated that the production of HMW adiponectin was increased, which indicates that T‑MSC CM may enhance adiponectin multimerization via amelioration of oxidative stress. Further studies are required to elucidate anti‑oxidant molecules secreted from T‑MSCs, and these results highlight the potential therapeutic relevance of T‑MSC CM for the treatment of obesity or obesity‑associated diseases.
“…Some of these distinctive markers include CD106 (VCAM‐1) and CD274 (PD‐L1), and have functions in adhesion and migration as well as immunomodulation . In fact, there are numerous studies describing the immunomodulatory properties of TMSCs, most of which are involved in the general downregulation of inflammatory responses .…”
Section: Tonsil‐derived Mscs (Tmscs)mentioning
confidence: 99%
“…TMSCs can also hinder dendritic cell (DC) maturation and CD4+ T‐cell differentiation , while increasing IL‐10‐producing regulatory B‐cells to downregulate the inflammatory response . At the same time, the inflammation may provide conditions for TMSCs to differentiate into follicular DCs , thereby inducing peripheral immune tolerance by interfering with the priming of alloreactive T‐cells . In a dextran sulfate sodium (DSS)‐induced colitis mice model, multiple intraperitoneal injections of TMSCs were shown to reduce gene expression of the inflammatory cytokines IL‐1β and IL‐6 consequently resolving the signs associated with the DSS‐induced colitis as evidenced from reduced disease activity index, rectal bleeding, and diarrhea .…”
Since the discovery of stem cells and multipotency characteristics of mesenchymal stem cells (MSCs), there has been tremendous development in regenerative medicine. MSCs derived from bone marrow have been widely used in various research applications, yet there are limitations such as invasiveness of obtaining samples, low yield and proliferation rate, and questions regarding their practicality in clinical applications. Some have suggested that MSCs from other sources, specifically those derived from palatine tonsil tissues, that is, tonsil-derived MSCs (TMSCs), could be considered as a new potential therapeutic tool in regenerative medicine due to their superior proliferation rate and differentiation capabilities with low immunogenicity and ease of obtaining. Several studies have determined that TMSCs have differentiation potential not only into the mesodermal lineage but also into the endodermal as well as ectodermal lineages, expanding their potential usage and placing them as an appealing option to consider for future studies in regenerative medicine. In this review, the differentiation capacities of TMSCs and their therapeutic competencies from past studies are addressed. STEM CELLS 2019;37:1252-1260
SIGNIFICANCE STATEMENTMesenchymal stem cells (MSCs) are considered as a great candidate for tissue engineering in regenerative medicine. Tonsil-derived MSCs (TMSCs) could be an attractive option for clinical applications because of their noninvasiveness of tissue collection, relatively high proliferation rate, and low allogenicity. This review addresses potential differentiation capabilities of TMSCs into mesodermal, endodermal, and ectodermal lineages reported from previous in vitro and in vivo studies as well as their potential applications for treating various human diseases.
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