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Extracellular vesicles from antler blastema progenitor cells reverse bone loss and improve aging-related phenotypes in mice and macaques

ABSTRACT: Extracellular vesicles from antler blastema progenitor cells reverse bone loss and improve aging-related phenotypes in mice and macaques

PROVIDER: PRJNA1220683 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32267900_1.fastq.gz	Fastqsanger.gz
	SRR32267900_2.fastq.gz	Fastqsanger.gz
	SRR32268000_1.fastq.gz	Fastqsanger.gz
	SRR32268000_2.fastq.gz	Fastqsanger.gz
	SRR32267901_1.fastq.gz	Fastqsanger.gz

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Extracellular vesicles from antler blastema progenitor cells reverse bone loss and improve aging-related phenotypes in mice and macaques

Project description:Antler blastema progenitor cell (ABPC) is a novel type of skeletal mesenchymal stem cell with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating molecules in EVsABPCs that differed from EVs of mouse bone marrow stromal stem cells (EVsBMSCs). EVsABPCs exhibited a robust in vitro ability to rejuvenate senescence BMSCs of aged mice and shift their molecular signature into a youthful state. In vivo, EVsABPCs increased bone mineral density in the femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed mouse fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation, and rejuvenating major tissues of elderly mice, with no observed immunological side effects. Furthermore, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. Particularly, EVsABPCs resulted in remarkable improvements in brain structure and behaviors of elderly rhesus macaques, providing the first batch of evidence of EVs’ beneficial effects on aging brains in primates. These findings suggest that the ABPC is a novel and practical source of EVs containing a wealth of systemic rejuvenating factors and has considerable translational value for anti-aging interventions, particularly the rejuvenation of aging bones.

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Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques

Project description:Antler blastema progenitor cell (ABPC) is a novel type of skeletal stem cells with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) can strongly rejuvenate aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating signals in EVsABPCs, which exhibited a robust in vitro ability to rejuvenate senescent bone marrow stromal stem cells. In vivo, EVsABPCs increased bone mineral density in femur by 2.4-fold in mice, and 1.53-fold in rhesus macaques. Besides, intravenous EVsABPCs significantly outperformed fetal-EVsBMSCs in improving physical performance, reducing systemic inflammation and rejuvenating major tissues of aged mice, with no observed immunological side effects. Notably, EVsABPCs showed similar rejuvenating effects in old rhesus macaques as in elderly mice. These findings suggest that ABPC is a novel and practical source of EVs containing unique rejuvenating factors and has considerable translational value for anti-aging interventions, particularly rejuvenation of aging bones.

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Extracellular vesicles from antler blastema progenitor cells improve age-related phenotypes in rodents and nonhuman primates

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Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques

Project description:Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging-related phenotypes in mice and macaques

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Extracellular vesicles from antler blastema progenitor cells reverse bone loss and mitigate aging related phenotypes in mice and macaques

Project description:Antler blastema progenitor cell (ABPC) is a novel type of skeletal mesenchymal stem cell with strong stemness and renewal ability. Here, we discovered that ABPC-derived extracellular vesicles (EVsABPCs) exerted strong geroprotective effect on aging tissues in aged mice and rhesus macaques (Macaca mulattas). We identified a variety of rejuvenating molecules in EVsABPCs that differed from those in EVs derived from rat bone marrow stromal stem cells (EVsBMSCs). In vitro, EVsABPCs rejuvenated senescent BMSCs and shifted their molecular signature towards a youthful state. In vivo, EVsABPCs increased femoral bone mineral density in mice and rhesus macaques by 2.5-fold and 1.5-fold, respectively. Besides, intravenous EVsABPCs significantly outperformed fetal-EVsBMSCs in improving physical performance, enhancing cognitive function, reducing systemic inflammation, and preserving major tissues in elderly mice. Notably, the aging clock highlights a roughly 3.54-months regression in overall aging in mice. Additionally, EVsABPCs showed similar geroprotective effects in elderly rhesus macaques, markedly improving locomotor performance and mitigating cortical volume atrophy. Conclusively, these findings suggest that the ABPC is a novel and practical source of EVs containing systemic rejuvenating factors and has considerable translational value for anti-aging interventions, particularly the rescue of aging bone.

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Extracellular vesicles from antler blastema progenitor cells improve age-related phenotypes in rodents and nonhuman primates

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Integrated miRNA-mRNA transcriptomic analysis reveals antler growth regulatory network [RNA-seq]

Project description:As the only regenerative organ of mammals, antler could grow rapidly without carcinogenesis. To understand the molecular mechanisms of the growth of sika deer antler, we used de novo RNA-seq analyses to determine the diﬀerential expression of unigenes and miRNAs from antler at 15, 60, 90, and 110-day. A total of 55004 unigenes, 208 known miRNAs and 38 novel miRNAs were identified. 10182 unigenes and 35 miRNAs were differentially expressed between 60-day and 15-day antler, 13258 unigenes and 53 miRNAs were differentially expressed between 90-day and 60-day antler, and 10740 unigenes and 27 miRNAs were differentially expressed between 110-day and 90-day antler. GO and KEGG analyses showed that DE unigenes and miRNA were mainly related to chondrogenesis, osteogenesis and inhibition of oncogenesis, that were closely associate with antler growth. We also constructed mRNA-mRNA and miRNA-mRNA interaction networks related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. The results showed that mRNA (COL2A1, SOX9, WWP2, FGFR1, SPARC, LOX etc.) and miRNAs (miR-145, miR-199a-3p, miR-140, miR-199a-5p etc.) may play important roles in chondrogenesis and osteogenesis of antler, and mRNA (TP53, Tpm3 and ATP1A1 etc.) and miRNAs (miR-106a, miR-145, miR-1260b and miR-2898 etc.) may have key roles in inhibiting the carcinogenesis of antlers. In this study, we identified miRNAs and unigenes related to chondrogenesis, osteogenesis and inhibition of oncogenesis of antler. This will provide a reference for in-depth analysis of the molecular mechanism of antler growth without carcinogenesis, and also provide valuable information for cartilage- and bone-related disease treatment, cancer treatment.

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