Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques

Tian, Chuan; He, Jie; An, Yuanyuan; Yang, Zailing; Yan, Donghai; Pan, Hang; Lv, Guanke; Li, Ye; Wang, Yanying; Yang, Yu-Kun; Zhu, Gaohong; He, Zhisong; Zhu, Xiaoyan; Pan, Xinghua

doi:10.1186/s13287-021-02486-4

Cited by 13 publications

(4 citation statements)

References 41 publications

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“…The conversion of a pluripotent VSEL with open chromatin into OSCs involves extensive epigenetic changes, and this process is affected by aging. Ovarian aging can be reversed by transplanting MSCs directly into the ovaries ( Tian et al, 2021 ; Wu et al, 2022 ) and by providing a younger niche. Aged ovaries possess rare premeiotic germ cells that can generate oocytes, following transplantation into a young host environment ( Niikura et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front “war” against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and “reprogram” into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the “light at the end of the tunnel.”

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Section: Introductionmentioning

confidence: 99%

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Bhartiya¹,

Jha²,

Tripathi³

et al. 2023

Front. Cell Dev. Biol.

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“…Mesenchymal stem cells (MSCs) have multidirectional differentiation potential and immune regulation capability, secreting a variety of bioactive factors and playing important roles in inflammation, tissue damage repair and aging degeneration. In a study of a rhesus monkey aging model [ [10] , [11] , [12] , [13] ], we found that bone marrow MSCs (BMMSCs) derived from infant rhesus monkeys restored the structure and function of aging ovaries by promoting follicular and vascular regeneration, reducing the degree of ovarian fibrosis, and inhibiting apoptosis; improved lung structure and function by reducing fibrosis and inhibiting apoptosis, enhancing the division and proliferation of alveolar type II epithelial cells and improving their antioxidative stress ability; and significantly reversed the expression of age-related proteins in serum. In our previous study, it was also observed that MSCs could improve the structure and function of the thymus in elderly mice [ 14 ], but this observation needed to be confirmed with further studies in nonhuman primates, which are more closely related to humans.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Yang,

Tian,

et al. 2024

Regenerative Therapy

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“…In recent years, many studies have investigated methods to improve ovarian functions, and the effects of stem cells or exosomes on ovarian functions have been well-documented ( 10 ). For example, human umbilical cord mesenchymal stem cell-derived exosomes can partly delay ovarian aging in female mice ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age

Liu

Zhou

et al. 2022

Front. Endocrinol.

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The reduction in the quantity and quality of oocytes is the major factor affecting fertility in women with advanced age, who tend to experience delayed childbearing and declined fertility rate. However, effective therapeutic strategies to combat this decrease in ovarian function are lacking in clinical practice. Thus, identifying a new method to rescue ovarian function and improve reproduction in natural age-related decline in fertility is necessary. Cell-free fat extract (CEFFE) has been verified to possess diverse active proteins exerting anti-aging and proliferation-promoting effects. Nonetheless, whether CEFFE can rescue the decline in aged-related ovarian function and improve the fertility of females with advanced age remains unclear. In this study, a natural aging mouse model, exhibiting similarities to the physiological changes of ovarian senescence, was used to observe the anti-aging effect of CEFFE on ovarian functions. We found that CEFFE, injected via the veins, could recover the levels of the sex hormone, increase angiogenesis and the number of growth follicles in the natural aging mice model. Moreover, CEFFE promoted the development of embryos and increased the litter size of aged mice. Transcriptome analysis of the aged mouse ovaries revealed that CEFFE treatment upregulated the expression of genes involved in the repair of DNA damage. And both in vivo and in vitro experiment proved that CEFFE improved the function of granulosa cells, including promoting proliferation, alleviating senescence, and rescuing DNA damage in aged granulosa cells. Collectively, our study implied that CEFFE improved the ovarian function and fertility of naturally aging mice by ameliorating the overall microenvironment of ovary, which provided a theoretical basis for new anti-aging therapeutic strategies for cell-free therapy in ovaries.

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Bone marrow mesenchymal stem cells derived from juvenile macaques reversed ovarian ageing in elderly macaques

Cited by 13 publications

References 41 publications

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age

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