Save your gut save your age: The role of the microbiome in stem cell ageing

Tan, Yi; Wei, Zongke; Chen, Jiaoliu; An, Junli; Li, Manling; Zhou, Liuyun; Men, Yanhua; Zhao, Shan

doi:10.1111/jcmm.14373

Cited by 23 publications

(12 citation statements)

References 100 publications

(186 reference statements)

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“…Besides, the microenvironment of bone marrow could be quite different among different ages which also affect the potential and biodistribution of stem cells. Several researchers investigated that older patients usually have complicated microenvironment changes characterized with dysregulation of metabolism and immune system influenced by various epigenetic factors and signaling networks [ 45 – 48 ]. In addition, different from our results, a previously [ 6 ] published guideline on ONFH suggested that effectiveness of stem cells are limited on preserving joint and the revision was relative high due to young patients.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

et al. 2020

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Background Osteonecrosis of femoral head (ONFH) is a seriously degenerative disease with no effective therapies to slow its progression. Several studies have reported short-term efficacy of stem cells on early-stage ONFH. However, its long-term effect was still unclear especially on progression events. This study was performed to evaluate the long-term efficacy and safety of stem cells and analyze its optimal age group and cell number. Methods Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42020136094. Following PRISMA guideline, we searched 8 electronic databases on January 5, 2020, and rigorous random controlled trials (RCTs) utilizing stem cell therapy on early-stage ONFH were included. Quality and bias were analyzed. Pooled analysis was performed to assess difference between various outcomes. Results A total of 13 RCTs (619 patients with 855 hips) were included. The application of stem cells significantly delayed collapse of femoral head(I2, 70%; RR, 0.54; 95% CI, 0.33 to 0.89; P < .00001) and total hip replacement (THR) (I2, 68%; RR, 0.55; 95% CI, 0.34 to 0.90; P = .02) in the long term. It effectively decreased the events of collapse of femoral head (≥ 60 months) (I2, 0%; RR, 0.37; 95% CI, 0.28 to 0.49; P < .00001) and THR (> 36 months) (I2, 0%; RR, 0.32; 95% CI, 0.23 to 0.44; P < .00001). There existed a beneficial effect for patients under 40 (Collapse of femoral head: I2, 56%; RR, 0.41; 95% CI, 0.23 to 0.76; P = .004) (THR: I2, 0%; RR, 0.31; 95% CI, 0.23 to 0.42; P < .00001). In addition, quantity of stem cells at 108 magnitude had better effects on disease progression events (I2, 0%; RR, 0.34; 95%CI, 0.16 to 0.74; P = .007). Besides, there were no significant differences on adverse events between the stem cell group and control group (I2, 0%; RR, 0.82; 95% CI, 0.39 to 1.73; P = .60). Conclusion Our findings build solid evidence that stem cell therapy could be expected to have a long-term effect on preventing early-stage ONFH patients from progression events, such as collapse of femoral head and total hip replacement. Furthermore, patients under 40 may be an ideal age group and the optimal cell number could be at 108 magnitude for this therapy. Further studies including strict RCTs are required to evaluate a clear effect of stem cells on ideal patient profile and the procedures of implantation.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

et al. 2020

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“…In conclusion, the analysis of the microbiomes of paired tonsil and saliva samples from Korean pediatric patients diagnosed with hyperplasia without tonsillitis revealed that many bacterial communities are shared and show similarities in terms of diversity and composition, suggesting close interactions between the two microbial groups. Although further studies are clearly essential, we assume that the oral microbiome exerts significant effects on not only the tonsil itself but also the tonsil-derived immune or stem cells by regulating the microbial community 46 , 47 . Our preliminary study may serve as a cornerstone in that it sheds light on the possibility of future research on novel microbiome-based therapeutic tactics using tonsil-derived cells or a tonsil-related microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Association between the microbiomes of tonsil and saliva samples isolated from pediatric patients subjected to tonsillectomy for the treatment of tonsillar hyperplasia

et al. 2020

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Oral microbes have the capacity to spread throughout the gastrointestinal system and are strongly associated with multiple diseases. Given that tonsils are located between the oral cavity and the laryngopharynx at the gateway of the alimentary and respiratory tracts, tonsillar tissue may also be affected by microbiota from both the oral cavity (saliva) and the alimentary tract. Here, we analyzed the distribution and association of the microbial communities in the saliva and tonsils of Korean children subjected to tonsillectomy because of tonsil hyperplasia (n = 29). The microbiome profiles of saliva and tonsils were established via 16S rRNA gene sequencing. Based on the alpha diversity indices, the microbial communities of the two groups showed high similarities. According to Spearman’s ranking correlation analysis, the distribution of Treponema, the causative bacterium of periodontitis, in saliva and tonsils was found to have a significant positive correlation. Two representative microbes, Prevotella in saliva and Alloprevotella in tonsils, were negatively correlated, while Treponema 2 showed a strong positive correlation between saliva and tonsils. Taken together, strong similarities in the microbial communities of the tonsils and saliva are evident in terms of diversity and composition. The saliva microbiome is expected to significantly affect the tonsil microbiome. Furthermore, we suggest that our study creates an opportunity for tonsillar microbiome research to facilitate the development of novel microbiome-based therapeutic strategies.

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“…The senescence associated secretory phenotype has been described to include matrix metalloproteinases (MMPs), which are potential candidates for tissue destruction and could be involved in affecting gut permeability 106 . Additionally, impaired pathogen clearance may also lead to changes in the microbiome, which has also been implicated in disrupting intestinal permeability 107,108 .…”

Section: Discussionmentioning

confidence: 99%

A subset of gut leukocytes have telomerase-dependent “hyper-long” telomeres and require telomerase for function in zebrafish

Ellis

Martins

Thompson

et al. 2022

Preprint

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Telomerase, the enzyme capable of elongating telomeres, is usually restricted in human somatic cells, which contributes to progressive telomere shortening with cell-division and ageing. Using the zebrafish model, we show that subsets gut immune cells have telomerase-dependent 'hyper-long' telomeres, which we identified as being predominantly macrophages and dendritics (mpeg1.1+ and cd45+mhcII+). Notably, mpeg1.1+ macrophages have much longer telomeres in the gut than in their haematopoietic tissue of origin, suggesting that there is a gut-specific modulation of telomerase in these cells. Moreover, we show that a subset of gut mpeg1.1+ cells express telomerase (tert) in young WT zebrafish, but that the relative proportion of these cells decreases with ageing. Importantly, this is accompanied by telomere shortening and DNA damage responses with ageing and a telomerase-dependent decrease in expression of autophagy and immune activation markers. Finally, these telomerase-dependent molecular alterations are accompanied by impaired phagocytosis of E.coli and increased gut permeability in vivo. Together, our data show that limiting levels of telomerase lead to changes in gut immunity and gut permeability, which, together, are likely contributors to local and systemic tissue degeneration and increased susceptibility to infection with ageing.

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Save your gut save your age: The role of the microbiome in stem cell ageing

Cited by 23 publications

References 100 publications

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

Efficacy and safety of stem cell therapy for the early-stage osteonecrosis of femoral head: a systematic review and meta-analysis of randomized controlled trials

Association between the microbiomes of tonsil and saliva samples isolated from pediatric patients subjected to tonsillectomy for the treatment of tonsillar hyperplasia

A subset of gut leukocytes have telomerase-dependent “hyper-long” telomeres and require telomerase for function in zebrafish

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