Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis

Takano, Tsunehiro; Li, Yin Ji; Kukita, Akiko; Yamaza, Takayoshi; Ayukawa, Yasunori; Moriyama, Kanako; Uehara, Norihisa; Nomiyama, Hisayuki; Koyano, Kiyoshi; Kukita, Toshio

doi:10.1038/labinvest.2013.152

Cited by 57 publications

(51 citation statements)

References 52 publications

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“…Importantly, it counteracts and overrides angiostatic stimuli, such as those from the CXCL10/CXCR3 axis [49]. CXCL12 also attracts mesenchymal stem cells to the inflammation sites, where they differentiate into osteoblasts and chondrocytes halting inflammatory bone destruction [50]. CXCL12 may decrease in situ inflammation through these highly immunosuppressive mesenchymal stem cells or by direct induction of Th1 repolarization [51, 52].…”

Section: Discussionmentioning

confidence: 99%

Low-dose methotrexate in sickle-cell disease: a pilot study with rationale borrowed from rheumatoid arthritis

et al. 2017

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BackgroundInflammation is a major feature of sickle cell disease (SCD). Low-dose methotrexate (MTX) has long been used in chronic inflammatory diseases. This pilot study examined the MTX effect on acute vaso-occlusive pain crises (VOC) in SCD patients.MethodsFourteen adults on hydroxyurea with severe and refractory VOC received one intramuscular injection of 10 mg of MTX per week for 12 weeks. A single weekly dose of 5 mg of leucovorin was administered orally 48 h after each MTX injection. The primary outcome was reduction in number/intensity of acute pain episodes. The secondary outcomes were improvement of quality of life (QOL) and reduction of the inflammatory status.ResultsMTX did not significantly change the median VOC frequency (12 before vs 10.5 during treatment, P = 0.6240) or the median McGill pain index (45 at week 0 vs 39.5 at week 12, P = 0.9311). However, there was a decrease of ≥50% in chronic pain resulting from avascular osteonecrosis (AVN) in 5 out of 7 patients with radiologic evidence of AVN, with the perception of longer pain-free periods. There was a 44.4% median gain in physical function in the SF-36 QOL questionnaire (P = 0.0198). MTX treatment up-regulated two C-X-C motif chemokines (CXCL), CXCL10 (P = 0.0463) and CXCL12 (P < 0.0001), without significant effect on 14 additional plasma inflammatory markers. Adverse events: One individual had fever of unknown origin. Respiratory tract infections were recorded in five patients. Among the latter, one also had dengue fever and another had a central venous line infection and died of pneumonia and septic shock. Three patients with previous history of hydroxyurea-induced hematological toxicity developed low blood platelet counts while receiving simultaneously MTX and hydroxyurea.ConclusionsAlthough MTX did not reduce acute VOC frequency/intensity, it decreased chronic pain and led to QOL improvement. Trial registration http://www.who.int/ictrp/en/ and http://www.ensaiosclinicos.gov.br, RBR-2s9xvn, 19 December 2016, retrospectively registeredElectronic supplementary materialThe online version of this article (doi:10.1186/s40164-017-0078-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Low-dose methotrexate in sickle-cell disease: a pilot study with rationale borrowed from rheumatoid arthritis

et al. 2017

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“…This may contribute to the recruitment of BMSCs to inflammatory sites in vivo. However, Ringe et al reported that human BMSCs did not migrate towards MCP-1 [49] and Takano et al reported similar findings with rat BMSCs [50].…”

Section: Discussionmentioning

confidence: 86%

Characterization of the immunomodulatory properties of alveolar bone-derived mesenchymal stem cells

2020

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Background: Recently, mesenchymal stem cells (MSCs) have been shown to have immunomodulatory properties which hold promise for their clinical use to treat inflammatory conditions. Relative to bone marrow-derived MSCs (BMSCs), which are typically isolated from the iliac crest, we have recently demonstrated that MSCs can be predictably isolated from the alveolar bone (aBMSCs) by less invasive means. As such, the aim of this study was to characterize the immunomodulatory properties of aBMSCs relative to BMSCs. Methods: aBMSCs isolated from the human alveolar bone and BMSCs isolated from the human bone marrow of the iliac crest were cultured in the same conditions. Cytokine arrays and enzyme-linked immunosorbent assays (ELISA) of a conditioned medium were used to evaluate differences in the secretion of cytokines. In different functional assays, aBMSCs and BMSCs were cocultured with different types of immune cells including THP-1 monocytes, macrophages, and peripheral blood mononuclear cells (PBMCs) to evaluate their effects on important immune cell functions including proliferation, differentiation, and activation. Results: The protein arrays identified interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 to be the major cytokines secreted by aBMSCs and BMSCs. ELISA determined that aBMSCs secreted 268.64 ± 46.96 pg/mL of IL-6 and 196.14 ± 97.31 pg/mL of MCP-1 per microgram of DNA, while BMSCs secreted 774.86 ± 414.29 pg/mL of IL-6 and 856.37 ± 433.03 pg/mL of MCP-1 per microgram of DNA. The results of the coculture studies showed that aBMSCs exhibited immunosuppressive effects on monocyte activation and T cell activation and proliferation similar to BMSCs. Both aBMSCs and BMSCs drove macrophages into an anti-inflammatory phenotype with increased phagocytic ability. Taken together, these data suggest that aBMSCs have potent immunomodulatory properties comparable to those of BMSCs. Conclusions:The findings of this study have important implications for the development of immunomodulatory stem cell therapies aimed to treat inflammatory conditions using aBMSCs, a more feasible tissue source of MSCs.

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“…that are taxing to a young healthy individual let alone older individuals [114][115][116]. A preemptive or perioperative administration of MSCs may dampen the immune response, aid in the healing process, and keep at-risk older individuals from declining in functional status (Table 2) [56,[117][118][119][120]. Given the results from the CRATUS, pilot dose finding [55] and randomized placebo controlled study [109] and the number of medical procedures older individuals undergo, large, randomized, double-blinded clinical trials are warranted to elucidate the efficacy of stem cell therapy in regard to the disease process in itself and its ability to suppress the progression of frailty after strenuous medical interventions.…”

Section: Resultsmentioning

confidence: 99%

Allogeneic Mesenchymal Stem Cells as a Treatment for Aging Frailty

Tompkins¹,

Landin²,

Florea³

et al. 2017

Frailty and Sarcopenia - Onset, Development and Clinical Challenges

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As life expectancy is projected to increase in the ensuing decades, individuals of older age continue to exceed the previous generation's lifespan. Advancing age is associated with a reduction in physical and mental functional capacity, and chronic inflammation is a major factor contributing to this decline. A heightened inflammatory state can lead to exhaustion, weakness, weight loss, slow gate speed, and an overall decrease in activity level. These phenotypes define the onset of the disease process known as frailty. Frailty is a growing epidemic, which severely undermines a person's ability to deal with outside stressors, and increases their rate of hospitalization, institutionalization, and mortality. Current interventions focus on preventative care by improving exercise capacity, strength, nutritional supplementation, diet, and mobility. However, a biological cure has heretofore remained elusive. Here, we introduce the novel therapeutic principle that mesenchymal stem cell (MSC) therapy may represent a safe, practical, and efficacious both the treatment and prevention of frailty in individuals of advancing age. To date, a phase I safety trial reveals an excellent safety profile and suggests that mesenchymal stem cells can ameliorate signs and symptoms of frailty. These early studies lay the groundwork for future large-scale clinical trials of this exciting and novel therapeutic concept that has the potential to expand health span in the aging population.

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Mesenchymal stem cells markedly suppress inflammatory bone destruction in rats with adjuvant-induced arthritis

Cited by 57 publications

References 52 publications

Low-dose methotrexate in sickle-cell disease: a pilot study with rationale borrowed from rheumatoid arthritis

Low-dose methotrexate in sickle-cell disease: a pilot study with rationale borrowed from rheumatoid arthritis

Characterization of the immunomodulatory properties of alveolar bone-derived mesenchymal stem cells

Allogeneic Mesenchymal Stem Cells as a Treatment for Aging Frailty

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