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Adipose-derived stem cells (ADSCs) have been documented as possible candidates for skin rejuvenation. However, the effects of ADSC-derived exosomes on photoaged skin remain to be fully elucidated. This study was aimed at determining the antiaging effects of ADSC-derived exosomes on photoaged skin. Human ADSCs were isolated from the adipose tissue of healthy women and cultured in vitro. Then, exosomes were extracted from the cultured ADSCs, purified by ultracentrifugation, and verified by examination of cell morphology using transmission electron microscopy and the identification of specific biomarkers. Meanwhile, the optimal exosome concentration and treatment time were selected. The photoaged skin model was created by subjecting Sprague-Dawley rats to ultraviolet B radiation. Exosomes were injected into the photoaged skin in a single therapeutic dose. The thickness of the epidermis and dermis was observed by HE staining. The relative mRNA expression of type I collagen, type III collagen, and matrix metalloproteinases (MMP-1 and MMP-3) was determined by real-time PCR. In the rat model of photoaged skin, the injected exosomes markedly decreased the epidermal thickness and increased the dermal thickness of the photoaged skin 7 days after treatment. Moreover, the proportion of the stratum corneum of the epidermis was decreased. Furthermore, real-time RT-PCR showed that the mRNA expression of type I collagen was increased and that of type III collagen, MMP-1, and MMP-3 was decreased. Our results demonstrate that ADSC-derived exosome treatment could significantly improve skin photodamage and that ADSC-derived exosomes may be a potential agent for photoaged skin treatment.

Background Recent evidence suggests that angiotensin II (Ang II) plays a role in cutaneous wound healing. Mesenchymal stem cells (MSCs) are known as a rich source of cells that re‐establish healed skin. However, the potential impact of Ang II on MSC differentiation into keratinocytes is still unknown. Objective The present study was conducted to explore the effect of Ang II on the differentiation of bone marrow‐derived MSCs (BM‐MSCs) into keratinocytes. Methods Bone marrow‐derived MSCs were isolated from rat bone marrow and cultured. The expression of Ang II type 1 (AT1) and type 2 (AT2) receptors was examined by immunofluorescence staining. The differentiation of BM‐MSCs into keratinocytes was investigated by flow cytometry or/and histological observation. Results The BM‐MSCs constitutively expressed both AT1 and AT2 receptors. The differentiation of BM‐MSCs into keratinocytes was successfully induced. Interestingly, incubation of BM‐MSCs with Ang II further promoted the differentiation of BM‐MSCs into keratinocyte, which was abolished by pretreament with losartan, an AT1 receptor antagonist, but not by PD123319, an AT2 receptor antagonist. Moreover, the p38 mitogen‐activated protein kinase (MAPK) inhibitor SB203580, the c‐Jun N‐terminal kinase (JNK) inhibitor SP600125 and the Janus‐activated kinase (JAK)2 inhibitor AG490 suppressed Ang II‐induced differentiation of BM‐MSCs into keratinocytes. The phosphoinositide‐3 kinase (PI3K) inhibitor wortmannin and MEK1/2 inhibitor U0126 had no effect on BM‐MSC differentiation into keratinocytes. Conclusions Our data demonstrated for the first time that Ang II plays a promotive role in the differentiation of BM‐MSC into keratinocytes through the AT1 receptor, and that the p38 MAPK, JNK and JAK2 signalling pathways are involved in this process.

ImportanceAlthough researchers have devoted substantial efforts, money, and time to studying the causes of dementia and the means to prevent it, no effective treatment exists yet. Identifying preclinical risk factors of dementia could help prevent or delay its progression.ObjectiveTo develop a point risk score prediction model of dementia.Design, Setting, and ParticipantsThis study used a large UK population-based prospective cohort study conducted between March 13, 2006, and October 1, 2010. Data analysis was performed from June 7 to September 15, 2021. Individual analyses of time end points were concluded at the first dementia diagnosis during the follow-up period. The data were split into training and testing data sets to separately establish and validate a prediction model.Main Outcomes and MeasuresOutcomes of interest included 5-, 9-, and 13-year dementia risk. Least absolute shrinkage and selection operator and multivariate Cox proportional hazards regression models were used to identify available and practical dementia predictors. A point risk score model was developed for the individual prediction of 5-, 9-, and 13-year dementia risk.ResultsA total of 502 505 participants were selected; the population after exclusions for missing data and dementia diagnosis at baseline was 444 695 (205 187 men; mean [SD] age, 56.74 [8.18] years; 239 508 women; mean [SD] age, 56.20 [8.01] years). Dementia occurrence during the 13 years of follow-up was 0.7% for men and 0.5% for women. The C statistic of the final multivariate Cox proportional hazards regression model was 0.86 for men and 0.85 for women in the training data set, and 0.85 for men and 0.87 for women in the testing data set. Men and women shared some modifiable risk and protective factors, but they also presented independent risk factors that accounted for 31.7% of men developing dementia and 53.35% of women developing dementia according to the weighted population-attributable fraction. The total point score of the risk score model ranged from −18 to 30 in men and −17 to 30 in women. The risk score model yielded nearly 100% prediction accuracy of 13-year dementia risk both in men and women.Conclusions and RelevanceIn this diagnostic study, a practical risk score tool was developed for individual prediction of dementia risk, which may help individuals identify their potential risk profile and provide guidance on precise and timely actions to promote dementia delay or prevention.