Bone Marrow Rejuvenation

Gong, Min; Yu, Bin; Wang, Yigang; Xu, Meifeng

doi:10.1253/circj.cj-13-1219

Cited by 5 publications

(2 citation statements)

References 15 publications

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“…However, given its self-renewing capacity, bone marrow manipulation may be a more practical method of reverse-engineering the effects of aging. Bone marrow rejuvenation increases angiogenic growth factor production and restores age-related deficits in angiogenesis and cardiac function after stress and injury [ 29 , 46 , 81 ], benefits that persisted up to a year. Heterochronic transplants also mitigate renal aging and increase bone mineral mass and fracture repair [ 3 , 98 , 101 ].…”

Section: Discussionmentioning

confidence: 99%

Aging alters the immunological response to ischemic stroke

et al. 2018

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The peripheral immune system plays a critical role in aging and in the response to brain injury. Emerging data suggest inflammatory responses are exacerbated in older animals following ischemic stroke; however, our understanding of these age-related changes is poor. In this work, we demonstrate marked differences in the composition of circulating and infiltrating leukocytes recruited to the ischemic brain of old male mice after stroke compared to young male mice. Blood neutrophilia and neutrophil invasion into the brain were increased in aged animals. Relative to infiltrating monocyte populations, brain-invading neutrophils had reduced phagocytic potential, and produced higher levels of reactive oxygen species and extracellular matrix-degrading enzymes (i.e., MMP-9), which were further exacerbated with age. Hemorrhagic transformation was more pronounced in aged versus young mice relative to infarct size. High numbers of myeloperoxidase-positive neutrophils were found in postmortem human brain samples of old (> 71 years) acute ischemic stroke subjects compared to non-ischemic controls. Many of these neutrophils were found in the brain parenchyma. A large proportion of these neutrophils expressed MMP-9 and positively correlated with hemorrhage and hyperemia. MMP-9 expression and hemorrhagic transformation after stroke increased with age. These changes in the myeloid response to stroke with age led us to hypothesize that the bone marrow response to stroke is altered with age, which could be important for the development of effective therapies targeting the immune response. We generated heterochronic bone marrow chimeras as a tool to determine the contribution of peripheral immune senescence to age- and stroke-induced inflammation. Old hosts that received young bone marrow (i.e., Young → Old) had attenuation of age-related reductions in bFGF and VEGF and showed improved locomotor activity and gait dynamics compared to isochronic (Old → Old) controls. Microglia in young heterochronic mice (Old → Young) developed a senescent-like phenotype. After stroke, aged animals reconstituted with young marrow had reduced behavioral deficits compared to isochronic controls, and had significantly fewer brain-infiltrating neutrophils. Increased rates of hemorrhagic transformation were seen in young mice reconstituted with aged bone marrow. This work suggests that age alters the immunological response to stroke, and that this can be reversed by manipulation of the peripheral immune cells in the bone marrow.Electronic supplementary materialThe online version of this article (10.1007/s00401-018-1859-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Aging alters the immunological response to ischemic stroke

et al. 2018

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“… 4 Moreover, most of the pluripotent stem cells, except for embryonic stem cells, are derived from the patients and possess the same genotype and phenotype, and thus are significantly valuable tools for studying the molecular mechanisms of the disease and for developing patient-specific therapy. 6 Stem cell therapy has demonstrated beneficial effects on several cardiovascular diseases including ischemic heart disease, 7 , 8 heart failure, 9 endothelial dysfunction, 10 , 11 peripheral artery disease, 12 , 13 atherosclerosis, 14 and pulmonary hypertension 15 , 16 ( Fig. 1 ).…”

Section: Introductionmentioning

confidence: 99%

The potential and challenges of using stem cells for cardiovascular repair and regeneration

2014

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Recent progress in using stem cells for tissue repair and functional restoration has aroused much attention due to its potential to provide a cue for many diseases such as myocardial infarction. Stem cell therapy for cardiovascular disease has been studied extensively at both experimental and clinical levels. Pluripotent stem cells and mesenchymal stem cells were proven to be effective for myocardial regeneration, angiogenesis, and cardiac functional restoration. In this review, we will concisely discuss advantages and disadvantages of currently-used stem cells for cardiovascular repair and regeneration. The limitations and uniqueness of some types of stem cells will also be discussed. Although substantial progress has been made over the last decade about stem cells in cardiovascular regeneration, many challenges lie ahead before the therapeutic potentials of stem cells can be fully recognized.

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Clinical limitation in stem cell therapy

Pandey

2024

Stem Cells

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Bone Marrow Rejuvenation

Cited by 5 publications

References 15 publications

Aging alters the immunological response to ischemic stroke

Aging alters the immunological response to ischemic stroke

The potential and challenges of using stem cells for cardiovascular repair and regeneration

Clinical limitation in stem cell therapy

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