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VAMSEE D. Myneni IAN MCCLAIN-CALDWELL DANIEL MARTIN LYNN VITALE-CROSS KAROLY MARKO JOSEPH M. FIRRIOLO BRIAN I. LABOW EVA MEZEY 《Cytotherapy》2019,21(2):148-161
Bone marrow–derived stromal cells or mesenchymal stromal cells (BMSCs or MSCs, as we will call them in this work) are multipotent progenitor cells that can differentiate into osteoblasts, adipocytes and chondrocytes. In addition, MSCs have been shown to modulate the function of a variety of immune cells. Donor age has been shown to affect the regenerative potential, differentiation, proliferation and anti-inflammatory potency of MSCs; however, the impact of donor age on their immunosuppressive activity is unknown. In this study, we evaluated the ability of MSCs derived from very young children and adults on T-cell suppression and cytokine secretion by monocytes/macrophages. MSCs were obtained from extra digits of children between 10 and 21 months and adults between 28 and 64 years of age. We studied cell surface marker expression, doubling time, lineage differentiation potential and immunosuppressive function of the MSCs. Young MSCs double more quickly and differentiate into bone and fat cells more efficiently than those from older donors. They also form more and dense colonies of fibroblasts (colony forming unit–fibroblast [CFU-F]). MSCs from both young and adult subjects suppressed T-cell proliferation in a mitogen-induced assay at 1:3 and 1:30 ratios. At a 1:30 ratio, however, MSCs from adults did not, but MSCs from infants did suppress T-cell proliferation. In the mixed lymphocyte reaction assay, MSCs from infants produced similar levels of suppression at all three MSC/T-cell ratios, but adult MSCs only inhibited T-cell proliferation at a 1:3 ratio. Cytokine analyses of co-cultures of MSCs and macrophages showed that both adult and young MSCs suppress tumor necrosis factor alpha (TNF-α) and induce interleukin-10 (IL-10) production in macrophage co-culture assay in a similar manner. Overall, this work shows that developing MSCs display a higher level of immunosuppression than mature MSCs. 相似文献
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KAZUHITO ICHII HIROFUMI HASHIMOTO† MICHAEL A. WHITE‡ CHRISTOPHER POTTER§ LUCY R. HUTYRA¶ ALFREDO R. HUETE RANGA B. MYNENI RAMAKRISHNA R. NEMANI§ 《Global Change Biology》2007,13(1):67-77
Accurate parameterization of rooting depth is difficult but important for capturing the spatio-temporal dynamics of carbon, water and energy cycles in tropical forests. In this study, we adopted a new approach to constrain rooting depth in terrestrial ecosystem models over the Amazon using satellite data [moderate resolution imaging spectroradiometer (MODIS) enhanced vegetation index (EVI)] and Biome-BGC terrestrial ecosystem model. We simulated seasonal variations in gross primary production (GPP) using different rooting depths (1, 3, 5, and 10 m) at point and spatial scales to investigate how rooting depth affects modeled seasonal GPP variations and to determine which rooting depth simulates GPP consistent with satellite-based observations. First, we confirmed that rooting depth strongly controls modeled GPP seasonal variations and that only deep rooting systems can successfully track flux-based GPP seasonality at the Tapajos km67 flux site. Second, spatial analysis showed that the model can reproduce the seasonal variations in satellite-based EVI seasonality, however, with required rooting depths strongly dependent on precipitation and the dry season length. For example, a shallow rooting depth (1–3 m) is sufficient in regions with a short dry season (e.g. 0–2 months), and deeper roots are required in regions with a longer dry season (e.g. 3–5 and 5–10 m for the regions with 3–4 and 5–6 months dry season, respectively). Our analysis suggests that setting of proper rooting depths is important to simulating GPP seasonality in tropical forests, and the use of satellite data can help to constrain the spatial variability of rooting depth. 相似文献
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IAN MCCLAIN-CALDWELL LYNN VITALE-CROSS BALAZS MAYER MIKLOS KREPUSKA MICHAEL BOYAJIAN VAMSEE MYNENI DANIEL MARTIN KAROLY MARKO KRISZTIAN NEMETH EVA MEZEY 《Cytotherapy》2018,20(12):1437-1444
Background aims
Bone marrow–derived mesenchymal stromal cells (MSCs) have been reported to suppress T-cell proliferation and used to alleviate the symptoms of graft-versus-host disease (GVHD). MSCs are a mixed cell population and at this time there are no tools to isolate the cells responsible for the T-cell suppression. We wanted to find a way to enhance the immune-modulatory actions of MSCs and tried varying the temperature at which they were cultured.Methods
We cultured human MSCs derived from healthy volunteers at different temperatures and tested their ability to switch macrophage character from pro-inflammatory to anti-inflammatory (M1 type to M2 type). Using an enzyme-linked immunosorbent assay (ELISA), we showed that when MSCs are cultured at higher temperatures their ability to induce co-cultured macrophages to produce more interleukin-10, (IL-10) (an anti-inflammatory cytokine) and less tumor necrosis factor alpha, (TNFα) (a pro-inflammatory cytokine) is increased. We performed Western blots and immunocytochemistry to screen for changes that might underlie this effect.Results
We found that in hyperthermia the heat shock protein, HSF1, translocated into the nucleus of MSCs. It appears to induce the COX2/PGE2 (Cyclooxygenase2/Prostaglandin E2) pathway described earlier as a major mechanism of MSC-directed immune-suppression.Conclusion
Hyperthermia increases the efficacy of MSC-driven immune-suppression. We propose that changing the time of MSC administration to patients to mid-to-late afternoon when the body temperature is naturally highest might be beneficial. Warming the patient could also be considered. 相似文献
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