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

Johnson, Adiv A.; Naaldijk, Yahaira; Hohaus, Christian; Meisel, Hans Jörg; Krystel, Ilona; Stolzing, Alexandra

doi:10.18632/aging.101035

Cited by 9 publications

(4 citation statements)

References 48 publications

(60 reference statements)

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“…Autologous stem cell transplantation is commonly performed with mesenchymal stem cells and numerous strategies have been devised to enhance their therapeutic efficacy. For example, pre-incubating stem cells with certain compounds can increase their genetic stability (Johnson et al, 2016) while rearing stem cells under specific conditions, such as hypoxia (Naaldijk et al, 2015), can enhance their transplantation efficiency.…”

Section: Prospective Therapiesmentioning

confidence: 99%

Bestrophin 1 and retinal disease

Johnson

Guziewicz

Lee

et al. 2017

Progress in Retinal and Eye Research

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Mutations in the gene BEST1 are causally associated with as many as five clinically distinct retinal degenerative diseases, which are collectively referred to as the “bestrophinopathies”. These five associated diseases are: Best vitelliform macular dystrophy, autosomal recessive bestrophinopathy, adult-onset vitelliform macular dystrophy, autosomal dominant vitreoretinochoroidopathy, and retinitis pigmentosa. The most common of these is Best vitelliform macular dystrophy. Bestrophin 1 (Best1), the protein encoded by the gene BEST1, has been the subject of a great deal of research since it was first identified nearly two decades ago. Today we know that Best1 functions as both a pentameric anion channel and a regulator of intracellular Ca2+ signaling. Best1 is an integral membrane protein which, within the eye, is uniquely expressed in the retinal pigment epithelium where it predominantly localizes to the basolateral plasma membrane. Within the brain, Best1 expression has been documented in both glial cells and astrocytes where it functions in both tonic GABA release and glutamate transport. The crystal structure of Best1 has revealed critical information about how Best1 functions as an ion channel and how Ca2+ regulates that function. Studies using animal models have led to critical insights into the physiological roles of Best1 and advances in stem cell technology have allowed for the development of patient-derived, “disease in a dish” models. In this article we review our knowledge of Best1 and discuss prospects for near-term clinical trials to test therapies for the bestrophinopathies, a currently incurable and untreatable set of diseases.

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Section: Prospective Therapiesmentioning

confidence: 99%

Bestrophin 1 and retinal disease

Johnson

Guziewicz

Lee

et al. 2017

Progress in Retinal and Eye Research

Self Cite

165

163

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“…The success of a given MSC transplantation therapy may depend on a variety of factors, such as whether or not they were pre-incubated with protective compounds [ 11 , 12 ] or under specific environmental conditions [ 13 ]. Another key factor underlying MSC transplantation efficiency may be the ability of MSCs to localize, or migrate, into target tissues of interest [ 14 ].…”

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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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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“…For example, some researchers found that the adipogenic differentiation potential of MSCs decreased with age, while another investigation demonstrated an increased ability with age (Zaim et al, 2012; Abuna et al, 2016). Also, a study showed that the abnormal expression in DNA break repair genes in MSCs was age‐related, while other studies revealed an unchanged result (Johnson et al, 2016; Khan et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

FAM96B inhibits the senescence of dental pulp stem cells

Liang

Yang

et al. 2020

Cell Biology International

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Dental pulp stem cells (DPSCs) are considered a remarkable source for the regeneration of dental pulp tissues, but their therapeutic effectiveness remains limited, especially in elderly people. Previous studies found that senescence has a negative effect on the proliferation and differentiation potential of DPSCs. Moreover, numerous long non-coding RNA (lncRNA) and messenger RNA were significantly differentially regulated in DPSCs from young and elderly donors. However, the changes in DPSCs protein during senescence have not been addressed. In this study, differences in DPSC protein expression profiles and coexpression of protein and lncRNA were analyzed using proteomics and bioinformatics. The results showed 75 upregulated proteins and 69 downregulated proteins in DPSCs from elderly donors. Vasopressin-regulated water reabsorption, Parkinson's disease, Alzheimer's disease, and protein export were the top four functional pathways associated with DPSCs. High mobility group N1 (HMGN1), HMGN2, UCHL1, and the family with sequence similarity 96 member B homeobox gene (FAM96B) were associated with DPSCs senescence. Then, we investigated FAM96B function in DPSCs. After FAM96B depletion, telomerase reverse transcriptase (TERT) activity decreased, but the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and the protein levels of p16, p53 were significantly increased. Gain-of-function assays suggested that FAM96B overexpression was positively correlated with TERT activity, but negatively correlated with the number of SA-β-gal positive cells and the protein levels of P16 and P53. Moreover, after FAM96B overexpression, the results showed a significant increase in alkaline phosphatase activity and an enhanced mineralization ability of DPSCs. The reverse-transcription polymerase chain reaction results also showed that dentin sialophosphoprotein and osteocalcin were expressed at greater levels. The carboxyfluorescein succinimidyl ester (CFSE) results displayed that FAM96B increased the proliferation potential of DPSCs. Our study revealed candidate proteins that might be related to DPSCs senescence and provided information to elucidate the mechanism of the biological changes in DPSCs' aging. Moreover, FAM96B was demonstrated to play an important role in suppressing DPSCs senescence and promoting osteogenic differentiation and proliferation.Abbreviations: DPSCs, dental pulp stem cells; FAM96B, the family with sequence similarity 96 member B homeobox gene; MSCs, mesenchymal stem cells; shRNAs, short-hairpin RNAs; TERT, telomerase reverse transcriptase † Hanbing Liang and Wenzhi Li contributed equally to this work.

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

Cited by 9 publications

References 48 publications

Bestrophin 1 and retinal disease

Bestrophin 1 and retinal disease

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

FAM96B inhibits the senescence of dental pulp stem cells

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