Tissue-Specific Ageing of Rat Tendon-Derived Progenitor Cells

Scutt, Nanette; Johnson, Adiv A.; Scutt, Andrew; Stolzing, Alexandra

doi:10.4172/2157-7633.1000309

Cited by 3 publications

(4 citation statements)

References 46 publications

(65 reference statements)

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“…More broadly, aging is known to exert negative effects on stem cells and progenitor cells [34–36]. Aging increases the susceptibility of MSCs to damaging agents like reactive oxygen species, disrupts cell population dynamics, diminishes therapeutic efficacy, and mediates other harmful effects [1, 37–39].…”

Section: Introductionmentioning

confidence: 99%

“…Although conflicting reports exist in the literature as to whether or not MSC migration is affected by aging [ 13 , 33 ], aging is known to detrimentally affect MSC functionality [ 1 ]. More broadly, aging is known to exert negative effects on stem cells and progenitor cells [ 34 – 36 ]. Aging increases the susceptibility of MSCs to damaging agents like reactive oxygen species, disrupts cell population dynamics, diminishes therapeutic efficacy, and mediates other harmful effects [ 1 , 37 – 39 ].…”

Section: Introductionmentioning

confidence: 99%

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Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

et al. 2017

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BackgroundMesenchymal stem cells (MSCs) show therapeutic efficacy in many different age-related degenerative diseases, including Alzheimer’s disease. Very little is currently known about whether or not aging impacts the transplantation efficiency of MSCs.MethodsIn this study, we investigated the distribution of intravenously transplanted syngeneic MSCs derived from young and aged mice into young, aged, and transgenic APP/PS1 Alzheimer’s disease mice. MSCs from male donors were transplanted into female mice and their distribution pattern was monitored by PCR using Y-chromosome specific probes. Biodistribution of transplanted MSCs in the brains of APP/PS1 mice was additionally confirmed by immunofluorescence and confocal microscopy.ResultsFour weeks after transplantation into young mice, young MSCs were found in the lung, axillary lymph nodes, blood, kidney, bone marrow, spleen, liver, heart, and brain cortex. In contrast, young MSCs that were transplanted into aged mice were only found in the brain cortex. In both young and aged mouse recipients, transplantation of aged MSCs showed biodistribution only in the blood and spleen. Although young transplanted MSCs only showed neuronal distribution in the brain cortex in young mice, they exhibited a wide neuronal distribution pattern in the brains of APP/PS1 mice and were found in the cortex, cerebellum, hippocampus, olfactory bulb, and brainstem. The immunofluorescent signal of both transplanted MSCs and resident microglia was robust in the brains of APP/PS1 mice. Monocyte chemoattractant-1 levels were lowest in the brain cortex of young mice and were significantly increased in APP/PS1 mice. Within the hippocampus, monocyte chemoattractant-1 levels were significantly higher in aged mice compared with younger and APP/PS1 mice.ConclusionsWe demonstrate in vivo that MSC biodistribution post transplantation is detrimentally affected by aging and neuronal health. Aging of both the recipient and the donor MSCs used attenuates transplantation efficiency. Clinically, our data would suggest that aged MSCs should not be used for transplantation and that transplantation of MSCs into aged patients will be less efficacious.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0533-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

et al. 2017

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“…This as well as other data indicate that age of the donor may impact the genomic integrity of reprogrammed iPSCs . Aging may also impact the functionality of other clinically relevant cells, such as progenitor cells . In fact, the age of the donor has been reported to impact the migration efficiency of transplanted mesenchymal stem cells, indicating that using stem cells derived from old donors may be less than ideal .…”

Section: Future Research and Directions For Quality Controlmentioning

confidence: 82%

Concise Review: Molecular Cytogenetics and Quality Control: Clinical Guardians for Pluripotent Stem Cells

Rohani

Johnson

Naghsh

et al. 2018

Stem Cells Translational Medicine

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Now that induced pluripotent stem cell (iPSC)‐based transplants have been performed in humans and organizations have begun producing clinical‐grade iPSCs, it is imperative that strict quality control standards are agreed upon. This is essential as both ESCs and iPSCs have been shown to accumulate genomic aberrations during long‐term culturing. These aberrations can include copy number variations, trisomy, amplifications of chromosomal regions, deletions of chromosomal regions, loss of heterozygosity, and epigenetic abnormalities. Moreover, although the differences between iPSCs and ESCs appear largely negligible when a high enough n number is used for comparison, the reprogramming process can generate further aberrations in iPSCs, including copy number variations and deletions in tumor‐suppressor genes. If mutations or epigenetic signatures are present in parental cells, these can also be carried over into iPSCs. To maximize patient safety, we recommend a set of standards to be utilized when preparing iPSCs for clinical use. Reprogramming methods that do not involve genomic integration should be used. Cultured cells should be grown using feeder‐free and serum‐free systems to avoid animal contamination. Karyotyping, whole‐genome sequencing, gene expression analyses, and standard sterility tests should all become routine quality control tests. Analysis of mitochondrial DNA integrity, whole‐epigenome analyses, as well as single‐cell genome sequencing of large cell populations may also prove beneficial. Furthermore, clinical‐grade stem cells need to be produced under accepted regulatory good manufacturing process standards. The creation of haplobanks that provide major histocompatibility complex matching is also recommended to improve allogeneic stem cell engraftment. Stem Cells Translational Medicine 2018;7:867–875

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“…Aging is a highly complex, multifaceted process characterized by the progressive decline in physiological integrity. Both genomic instability and stem cell exhaustion are two established hallmarks of aging [ 20 , 39 , 40 ]. Given this, we were surprised to find that age of the MSC donor failed to significantly impact tail length, tail DNA, or OTM in ADSCs subjected to genotoxic stress.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of alpha phenyl-tert-butyl nitrone and ascorbic acid in human adipose derived mesenchymal stem cells from differently aged donors

Johnson

Naaldijk

Hohaus

et al. 2016

Aging

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Adipose-derived mesenchymal stem cells (ADSCs) are multipotent stem cells that promote therapeutic effects and are frequently used in autologous applications. Little is known about how ADSCs respond to genotoxic stress and whether or not donor age affects DNA damage and repair. In this study, we used the comet assay to assess DNA damage and repair in human ADSCs derived from young (20-40 years), middle-aged (41-60 years), and older (61+ years) donors following treatment with H2O2 or UV light. Tail lengths in H2O2-treated ADSCs were substantially higher than the tail lengths in UV-treated ADSCs. After 30 minutes of treatment with H2O2, ADSCs preconditioned with alpha phenyl-tert-butyl nitrone (PBN) or ascorbic acid (AA) showed a significant reduction in % tail DNA. The majority of ADSCs treated with PBN or AA displayed low olive tail movements at various timepoints. In general and indicative of DNA repair, % tail length and % tail DNA peaked at 30 minutes and then decreased to near-control levels at the 2 hour and 4 hour timepoints. Differently aged ADSCs displayed comparable levels of DNA damage in the majority of these experiments, suggesting that the age of the donor does not affect the DNA damage response in cultured ADSCs.

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Tissue-Specific Ageing of Rat Tendon-Derived Progenitor Cells

Cited by 3 publications

References 46 publications

Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

Concise Review: Molecular Cytogenetics and Quality Control: Clinical Guardians for Pluripotent Stem Cells

Protective effects of alpha phenyl-tert-butyl nitrone and ascorbic acid in human adipose derived mesenchymal stem cells from differently aged donors

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