A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

Sonoda, Soichiro; Yamaza, Takayoshi

doi:10.3390/ijms23073479

Cited by 8 publications

(10 citation statements)

References 79 publications

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“…MSCs exhibit an immunomodulatory property to a variety of immune cells, such as T lymphocytes, B lymphocytes, and macrophages ( 45 , 46 ). The immunosuppressive functions of MSCs are explained by the following three mechanisms: 1) indirect intercellular communications with innate and adaptive immune cells by paracrine factors, including growth factors, cytokines, and container within EVs, such as miRNA; 2) direct intercellular communications with T lymphocytes through cell surface molecules, such as FasL and program death ligand 1; 3) efferocytosis of T lymphocyte-induced ApBs of MSCs, followed by secreting immunosuppressive factors from phagocytes ( 23 , 47 ).…”

Section: A Novel Mechanism Of Msc-ev Therapy Through Microenvironment...mentioning

confidence: 99%

“…In the following literature, we discuss a unique mechanism of action of SHED-EV therapy for osteopenia treatment, which rejuvenate the bone marrow microenvironment through recipient BMMSCs ( 40 , 47 , 92 ).…”

Section: A Novel Mechanism Of Msc-ev Therapy Through Microenvironment...mentioning

confidence: 99%

“…Increasing studies report SHED-EVs carry in vitro and in vivo biological actions of SHED (47,85). SHED-EV-containing various bioactive molecules, such as nucleic acids and protein, are transported to target cells selectively by an unknown mechanism, resulting in implicating cell-cell communication, signal t r a n s d u c t i o n , i m m u n e m o d u l a t i o n , a n d e p i g e n e t i c reprogramming of recipient cells.…”

Section: Systemic Administration Of Stem Cellsmentioning

confidence: 99%

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Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment

Sonoda

Yamaza

2023

Front. Endocrinol.

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Systemic transplantation of mesenchymal stem cells (MSCs), such as bone marrow MSCs (BMMSCs) and stem cells from human exfoliated deciduous teeth (SHED), is considered a prominent treatment for osteopenia. However, the mechanism of action of the transplanted MSCs has been poorly elucidated. In the recipient target tissue, including bone and bone marrow, only a few donor MSCs can be detected, suggesting that the direct contribution of donor MSCs may not be expected for osteopenia treatment. Meanwhile, secretomes, especially contents within extracellular vesicles (EVs) released from donor MSCs (MSC-EVs), play key roles in the treatment of several diseases. In this context, administrated donor MSC-EVs may affect bone-forming function of recipient cells. In this review, we discuss how MSC-EVs contribute to bone recovery recipient tissue in osteopenia. We also summarize a novel mechanism of action of systemic administration of SHED-derived EVs (SHED-EVs) in osteopenia. We found that reduced telomerase activity in recipient BMMSCs caused the deficiency of microenvironmental modulating function, including bone and bone marrow-like niche formation and immunomodulation in estrogen-deficient osteopenia model mice. Systemic administration of SHED-EVs could exert therapeutic effects on bone reduction via recovering the telomerase activity, leading to the rejuvenation of the microenvironmental modulating function in recipient BMMSCs, as seen in systemic transplantation of SHED. RNase-preconditioned donor SHED-EVs diminished the therapeutic benefits of administrated SHED-EVs in the recipient osteopenia model mice. These facts suggest that MSC-EV therapy targets the recipient BMMSCs to rejuvenate the microenvironmental modulating function via telomerase activity, recovering bone density. We then introduce future challenges to develop the reproducible MSC-EV therapy in osteopenia.

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Section: A Novel Mechanism Of Msc-ev Therapy Through Microenvironment...mentioning

confidence: 99%

Section: A Novel Mechanism Of Msc-ev Therapy Through Microenvironment...mentioning

confidence: 99%

Section: Systemic Administration Of Stem Cellsmentioning

confidence: 99%

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Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment

Sonoda

Yamaza

2023

Front. Endocrinol.

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“…hDPSCs have shown higher growth potential than human bone marrow-derived stem cells (hBMSCs). Meanwhile, hDPSCs have been shown to have potent immunomodulatory functions in treating systemic lupus erythematosus (SLE) in the SLE MRL/lpr mouse model ( 6 ). Yan et al also indicated that hDPSCs could inhibit the progression of fibrosis in hypertrophic keloids ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling

Liu¹,

Li²,

Chen³

et al. 2023

Ann Transl Med

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Background Periodontitis is a major oral condition and current treatment outcomes can be unsatisfactory. Macrophages are essential to the regeneration process, so we investigated the influence of human dental pulp stem cells (hDPSCs) on macrophage differentiation and the microenvironment and the underlying mechanism. Methods hDPSCs were isolated from healthy third molars extracted from patients undergoing maxillofacial surgery. The surface antigens CD73, CD45, CD90 and CD11b of the hDPSCs were detected using flow cytometry. hDPSCs were induced for osteogenic and adipogenic differentiation, and the outcome was assessed by alizarin red staining or Oil Red O staining. The IL-6 level released by hDPSCs was measured by enzyme linked immunosorbent assay (ELISA). Tohoku Hospital Pediatrics-1 (THP-1) cells were cultured and induced into macrophages by phorbol-12-myristate-13-acetate. After coculture of THP-1-derived macrophages with hDPSCs, interleukin 6 (IL-6), Argininase-1 (Arg-1), Mannose receptor C-1 (Mrc-1), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) levels in the medium were measured using ELISA and quantificational RT-PCR (qRT-PCR). The numbers of CD80 + and CD163 + macrophages were counted by immunofluorescence, and GP130/STAT3 signaling protein expression was detected. After coculturing the culture medium of hDPSCs with human bone marrow stem cells (BMSCs), scratch assays and transwell assays were performed to evaluate cell migration and invasion. Results Alkaline phosphatase (ALP) staining, alizarin red staining, and western blots were performed to assess osteoblast differentiation. The hDPSCs were positive for surface antigens CD73 and CD90 and negative for CD45 and CD11b expression. The level of IL-6 secreted by hDPSCs significantly increased the number of CD80 + cells as well as the levels of Arg-1 and Mrc-1. It also promoted M2 macrophage polarization and activated GP130/STAT3 signaling. However, the medium cocultured with THP-1-derived macrophages by hDPSCs facilitated the migration, invasion, and osteogenic abilities of human bone marrow-derived stem cells (hBMSCs). Conclusions hDPSCs can regulate the periodontal microenvironment through IL-6 by inducing phenotypic transformation of M2 macrophages and stimulating osteogenic differentiation of BMSCs.

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“…In addition, hDPSC can release soluble immunosuppressive molecules such as prostaglandin E2 (PGE2), transforming growth factor β (TGF-β), and nitric oxide (NO) in a paracrine manner to suppress the T cell inflammatory response [ 18 ]. Studies have reported that hDPSC is able to treat a variety of autoimmune and inflammation-related diseases in vivo and vitro [ 19 , 20 ]. However, studies on the treatment of psoriasis by hDPSC have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice

Wen¹,

Li²,

Chen³

et al. 2023

Heliyon

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A New Target of Dental Pulp-Derived Stem Cell-Based Therapy on Recipient Bone Marrow Niche in Systemic Lupus Erythematosus

Cited by 8 publications

References 79 publications

Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment

Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment

Dental pulp stem cells induce anti-inflammatory phenotypic transformation of macrophages to enhance osteogenic potential via IL-6/GP130/STAT3 signaling

Human dental pulp stem cells ameliorate the imiquimod-induced psoriasis in mice

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