Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice

Kovina, Marina V.; Карнаухов, А. В.; Крашенинников, М. Е.; Kovin, Artem L.; Gazheev, Sarul T.; Sergievich, L. A.; Karnaukhova, E. V.; Богданенко, Е. В.; Balyasin, Maxim; Khodarovich, Yu. M.; Dyuzheva, T. G.; Lyundup, Alexey

doi:10.3389/fgene.2019.00310

Cited by 15 publications

(10 citation statements)

References 23 publications

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“…These findings are consistent with the results of the pilot study with i.c.v. infusion of bone marrow‐derived mouse stem cells obtained from mutants expressing green fluorescent protein (GFP) (see Data S1; Figure S3,)These experiments showed that i.c.v. administration of Neuro‐Cells to mice at the concentrations 100 000‐500 000 is well tolerated.…”

Section: Methodsmentioning

confidence: 99%

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

et al. 2019

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Aims:Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. Methods: FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 10 6 mesenchymal and hemopoietic human stem cells, containing 5 × 10 5 of CD34 + cells), which showed antiinflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle.Results: All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Celltreated mutants had reduced muscle atrophy and lumbar motor neuron degeneration.This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. Conclusion:The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation. | 505MUNTER ET al.

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Section: Methodsmentioning

confidence: 99%

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

et al. 2019

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“…4a). This higher number of donor HSCs allowed on average equal high engraftment of recipients of both aged and CASIN mice, excluding that differences in engraftment levels or a low engraftment level would bias the survival outcome 53 (Fig. 6b).…”

Section: Casin Treatment Restores a Youthful Transcriptional Heteroge...mentioning

confidence: 98%

Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice

et al. 2022

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One goal of regenerative medicine is to rejuvenate tissues and extend lifespan by restoring the function of endogenous aged stem cells. However, evidence that somatic stem cells can be targeted in vivo to extend lifespan is still lacking. Here, we demonstrate that after a short systemic treatment with a specific inhibitor of the small RhoGTPase Cdc42 (CASIN), transplanting aged hematopoietic stem cells (HSCs) from treated mice is sufficient to extend the healthspan and lifespan of aged immunocompromised mice without additional treatment. In detail, we show that systemic CASIN treatment improves strength and endurance of aged mice by increasing the myogenic regenerative potential of aged skeletal muscle stem cells. Further, we show that CASIN modifies niche localization and H4K16ac polarity of HSCs in vivo. Single-cell profiling reveals changes in HSC transcriptome, which underlie enhanced lymphoid and regenerative capacity in serial transplantation assays. Overall, we provide proof-of-concept evidence that a short systemic treatment to decrease Cdc42 activity improves the regenerative capacity of different endogenous aged stem cells in vivo, and that rejuvenated HSCs exert a broad systemic effect sufficient to extend murine health- and lifespan.

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“…It is the delivery method and subsequent stable engraftment of these cells to the bone marrow that is the limiting factor in moving this type of cell therapy from the lab to the clinic. To circumvent the toxic effect of radiation, other models of HSC replacement therapy have been proposed including nonmyeloablative transplantation, anti-cKit and anti-CD47 antibody-mediated HSC depletion or mobilization based-transplant [215][216][217]. In nonmyeloablative transplantation, the therapy relies on our understanding that the signals which retain HSCs to the niche are defective with age [107].…”

Section: Bone Marrow Transplant and Niche Remodelingmentioning

confidence: 99%

“…While the strategy can extend rodent lifespan, the efficacy is still low, potentially because of the age-related expansion of bone marrow MSCs [124]. However, using this approach, Kovina et al showed that transplantation of whole BM, not just purified HSCs, resulted in 28% chimerism 6 months post-transplant [215]. They attributed this high rate of chimerism to the age of the recipient (B10-GFP mice, 15 months old).…”

Section: Bone Marrow Transplant and Niche Remodelingmentioning

confidence: 99%

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

Tobin

Alibhai

Weisel

et al. 2020

Cells

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The importance of the immune system for cardiac repair following myocardial infarction is undeniable; however, the complex nature of immune cell behavior has limited the ability to develop effective therapeutics. This limitation highlights the need for a better understanding of the function of each immune cell population during the inflammatory and resolution phases of cardiac repair. The development of reliable therapies is further complicated by aging, which is associated with a decline in cell and organ function and the onset of cardiovascular and immunological diseases. Aging of the immune system has important consequences on heart function as both chronic cardiac inflammation and an impaired immune response to cardiac injury are observed in older individuals. Several studies have suggested that rejuvenating the aged immune system may be a valid therapeutic candidate to prevent or treat heart disease. Here, we review the basic patterns of immune cell behavior after myocardial infarction and discuss the autonomous and nonautonomous manners of hematopoietic stem cell and immune cell aging. Lastly, we identify prospective therapies that may rejuvenate the aged immune system to improve heart function such as anti-inflammatory and senolytic therapies, bone marrow transplant, niche remodeling and regulation of immune cell differentiation.

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Extension of Maximal Lifespan and High Bone Marrow Chimerism After Nonmyeloablative Syngeneic Transplantation of Bone Marrow From Young to Old Mice

Cited by 15 publications

References 23 publications

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Neuro‐Cells therapy improves motor outcomes and suppresses inflammation during experimental syndrome of amyotrophic lateral sclerosis in mice

Transplanting rejuvenated blood stem cells extends lifespan of aged immunocompromised mice

Considering Cause and Effect of Immune Cell Aging on Cardiac Repair after Myocardial Infarction

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