scholarly journals Age-Related Lipid Metabolic Signature in HumanLMNA-Lipodystrophic Stem Cell-Derived Adipocytes

2015 ◽  
Vol 100 (7) ◽  
pp. E964-E973 ◽  
Author(s):  
Patricia Sánchez ◽  
Arantza Infante ◽  
Garbiñe Ruiz de Eguino ◽  
Jorge A. Fuentes-Maestre ◽  
José Manuel García-Verdugo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Metabolic Signature ◽  
Age Related

scholarly journals Antioxidant Effects of Caffeic Acid Lead to Protection of Drosophila Intestinal Stem Cell Aging

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao Sheng ◽  
Yuedan Zhu ◽  
Juanyu Zhou ◽  
La Yan ◽  
Gang Du ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Caffeic Acid ◽  
Stress Responses ◽  
Adult Stem Cells ◽  
Cell Function ◽  
Cell Aging ◽  
Positive Effects ◽  
Age Related ◽  
Tissue Aging

The dysfunction or exhaustion of adult stem cells during aging is closely linked to tissue aging and age-related diseases. Circumventing this aging-related exhaustion of adult stem cells could significantly alleviate the functional decline of organs. Therefore, identifying small molecular compounds that could prevent the age-related decline of stem cell function is a primary goal in anti-aging research. Caffeic acid (CA), a phenolic compound synthesized in plants, offers substantial health benefits for multiple age-related diseases and aging. However, the effects of CA on adult stem cells remain largely unknown. Using the Drosophila midgut as a model, this study showed that oral administration with CA significantly delayed age-associated Drosophila gut dysplasia caused by the dysregulation of intestinal stem cells (ISCs) upon aging. Moreover, administering CA retarded the decline of intestinal functions in aged Drosophila and prevented hyperproliferation of age-associated ISC by suppressing oxidative stress-associated JNK signaling. On the other hand, CA supplementation significantly ameliorated the gut hyperplasia defect and reduced environmentally induced mortality, revealing the positive effects of CA on tolerance to stress responses. Taken together, our findings report a crucial role of CA in delaying age-related changes in ISCs of Drosophila.

Human Pluripotent Stem Cell Strategies for Age-Related Macular Degeneration

2014 ◽  
Vol 91 (8) ◽  
pp. 887-893 ◽  
Author(s):  
Kathryn C. Davidson ◽  
Robyn H. Guymer ◽  
Martin F. Pera ◽  
Alice Pébay
Keyword(s):  
Stem Cell ◽  
Macular Degeneration ◽  
Pluripotent Stem Cell ◽  
Age Related Macular Degeneration ◽  
Human Pluripotent Stem Cell ◽  
Age Related

scholarly journals A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1051 ◽  
Author(s):  
Daniel Contaifer ◽  
Catherine H. Roberts ◽  
Naren Gajenthra Kumar ◽  
Ramesh Natarajan ◽  
Bernard J. Fisher ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Stem Cell ◽  
Risk Stratification ◽  
Metabolic Profile ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Metabolic Signature ◽  
Chromatography Mass Spectrometry ◽  
The Impact

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity.

scholarly journals Engraftment of rare, pathogenic donor hematopoietic mutations in unrelated hematopoietic stem cell transplantation

2020 ◽  
Vol 12 (526) ◽  
pp. eaax6249 ◽  
Author(s):  
Wing Hing Wong ◽  
Sima Bhatt ◽  
Kathryn Trinkaus ◽  
Iskra Pusic ◽  
Kevin Elliott ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
High Throughput Sequencing ◽  
Limit Of Detection ◽  
Cell Transplant ◽  
Younger Adults ◽  
Hematopoietic Stem ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Over Time

Clonal hematopoiesis is associated with various age-related morbidities. Error-corrected sequencing (ECS) of human blood samples, with a limit of detection of ≥0.0001, has demonstrated that nearly every healthy individual >50 years old harbors rare hematopoietic clones below the detection limit of standard high-throughput sequencing. If these rare mutations confer survival or proliferation advantages, then the clone(s) could expand after a selective pressure such as chemotherapy, radiotherapy, or chronic immunosuppression. Given these observations and the lack of quantitative data regarding clonal hematopoiesis in adolescents and young adults, who are more likely to serve as unrelated hematopoietic stem cell donors, we completed this pilot study to determine whether younger adults harbored hematopoietic clones with pathogenic mutations, how often those clones were transferred to recipients, and what happened to these clones over time after transplantation. We performed ECS on 125 blood and marrow samples from 25 matched unrelated donors and recipients. Clonal mutations, with a median variant allele frequency of 0.00247, were found in 11 donors (44%; median, 36 years old). Of the mutated clones, 84.2% of mutations were predicted to be molecularly pathogenic and 100% engrafted in recipients. Recipients also demonstrated de novo clonal expansion within the first 100 days after hematopoietic stem cell transplant (HSCT). Given this pilot demonstration that rare, pathogenic clonal mutations are far more prevalent in younger adults than previously appreciated, and they engraft in recipients and persist over time, larger studies with longer follow-up are necessary to correlate clonal engraftment with post-HSCT morbidity.

scholarly journals Stem Cell-Derived Exosomes Prevent Aging-Induced Cardiac Dysfunction through a Novel Exosome/lncRNA MALAT1/NF-κB/TNF-α Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Bao Zhu ◽  
Lulu Zhang ◽  
Chun Liang ◽  
Bin Liu ◽  
Xiangbin Pan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Signaling Pathway ◽  
Cardiac Dysfunction ◽  
Human Umbilical Cord ◽  
Beneficial Effects ◽  
Age Related ◽  
Lncrna Malat1 ◽  
Tnf Α ◽  
Heart Functions

Aging is a risk factor for cardiovascular disease, and there is no effective therapeutic approach to alleviate this condition. NF-κB and TNF-α have been implicated in the activation of the aging process, but the signaling molecules responsible for the inactivation of NF-κB and TNF-α remain unknown. Exosomes have been reported to improve heart functions by releasing miRNA. Recent studies suggest that lncRNAs are more tissue-specific and developmental stage-specific compared to miRNA. However, the role of lncRNA in exosome-mediated cardiac repair has not been explored. In the present study, we focused on metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), which is an lncRNA associated with cell senescence. We discovered that human umbilical cord mesenchymal stem cell- (UMSC-) derived exosomes prevent aging-induced cardiac dysfunction. Silencer RNA against lncRNA MALAT1 blocked the beneficial effects of exosomes. In summary, we discovered that UMSC-derived exosomes prevent aging-induced cardiac dysfunction by releasing novel lncRNA MALAT1, which in turn inhibits the NF-κB/TNF-α signaling pathway. These findings will lead to the development of therapies that delay aging and progression of age-related diseases.

scholarly journals Quantifying Microsatellite Mutation Rates from Intestinal Stem Cell Dynamics in Msh2-Deficient Murine Epithelium

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 655-665 ◽  
Author(s):  
Joseph Christopher ◽  
Ann-Sofie Thorsen ◽  
Sam Abujudeh ◽  
Filipe C. Lourenço ◽  
Richard Kemp ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fold Increase ◽  
Mutation Rates ◽  
Wild Type ◽  
Cell Dynamics ◽  
Tissue Samples ◽  
Age Related ◽  
Increased Risk ◽  
Microsatellite Mutation ◽  
Risk Of Cancer

Microsatellite sequences have an enhanced susceptibility to mutation, and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here, we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed, and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus, and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (∼50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2-deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 × 10−2) compared to wild-type epithelium (6.2 × 10−5).

Stem Cell Therapy for the Treatment of Dry Age-Related Macular Degeneration

2015 ◽  
Vol 3 (1) ◽  
pp. 16-25
Author(s):  
Lisa C. Olmos ◽  
Hossein Nazari ◽  
Damien C. Rodger ◽  
Mark S. Humayun
Keyword(s):  
Stem Cell ◽  
Cell Therapy ◽  
Macular Degeneration ◽  
Stem Cell Therapy ◽  
Age Related Macular Degeneration ◽  
Age Related
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