Physical modulation of mesenchymal stem cell exosomes: A new perspective for regenerative medicine.

Mesenchymal stem cell-derived exosomes (MSC-Exo) offer promising therapeutic potential for various refractory diseases, presenting a novel therapeutic strategy. However, their clinical application encounters several obstacles, including low natural secretion, uncontrolled biological functions and inherent heterogeneity. On the one hand, physical stimuli can mimic the microenvironment dynamics where MSC-Exo reside. These factors influence not only their secretion but also, significantly, their biological efficacy. Moreover, physical factors can also serve as techniques for engineering exosomes. Therefore, the realm of physical factors assumes a crucial role in modifying MSC-Exo, ultimately facilitating their clinical translation. This review focuses on the research progress in applying physical factors to MSC-Exo, encompassing ultrasound, electrical stimulation, light irradiation, intrinsic physical properties, ionizing radiation, magnetic field, mechanical forces and temperature. We also discuss the current status and potential of physical stimuli-affected MSC-Exo in clinical applications. Furthermore, we address the limitations of recent studies in this field. Based on this, this review provides novel insights to advance the refinement of MSC-Exo as a therapeutic approach in regenerative medicine.

Adipose-derived mesenchymal stem cell therapy for reverse bleomycin-induced experimental pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive respiratory disease. Arguably, the complex interplay between immune cell subsets, coupled with an incomplete understanding of disease pathophysiology, has hindered the development of successful therapies. Despite efforts to understand its pathophysiology and develop effective treatments, IPF remains a fatal disease, necessitating the exploration of new treatment options. Mesenchymal stromal/stem cell (MSC) therapy has shown promise in experimental models of IPF, but further investigation is needed to understand its therapeutic effect. This study aimed to assess the therapeutic effect of adipose-derived mesenchymal stem cells in a bleomycin-induced pulmonary fibrosis model. First, MSC cells were obtained from mice and characterized using flow cytometry and cell differentiation culture methods. Then adult C57BL/6 mice were exposed to endotracheal instillation of bleomycin and concurrently treated with MSCs for reversal models on day 14. Experimental groups were evaluated on days 14, 21, or 28. Additionally, lung fibroblasts challenged with TGF-ß1 were treated with MSCs supernatant or MSCs to explore the mechanisms underlying of pulmonary fibrosis reversal. Mesenchymal stem cells were successfully isolated from mouse adipose tissue and characterized based on their differentiation ability and cell phenotype. The presence of MSCs or their supernatant stimulated the proliferation and migration of lung fibrotic cells. MSCs supernatant reduced lung collagen deposition, improved the Ashcroft score and reduced the gene and protein expression of lung fibrosis-related substances. Bleomycin-challenged mice exhibited severe septal thickening and prominent fibrosis, which was effectively reversed by MSCs treatment. MSC supernatant could suppress the TGF-ß1/Smad signaling pathway and supernatant promotes fibroblast autophagy. In summary, this study demonstrates that MSCs supernatant treatment is as effective as MSCs in revert the core features of bleomycin-induced pulmonary fibrosis. The current study has demonstrated that MSCs supernatant alleviates the BLM-induced pulmonary fibrosis in vivo. In vitro experiments further reveal that MSC supernatant could suppress the TGF-ß1/Smad signaling pathway to inhibit the TGF-ß1-induced fibroblast activation, and promotes fibroblast autophagy by Regulating p62 expression. These findings contribute to the growing body of evidence supporting the therapeutic application of MSCs in cell therapy medicine for IPF.

Trends in cutaneous squamous cell carcinoma on the lip incidence and mortality in the United States, 2000-2019.

Objective: This study provided a systematic analysis of the trend in incidence and incidence-based mortality for cutaneous squamous cell carcinoma (cSCC) on the lips in the USA using demographic characteristics from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Patients diagnosed with cSCC on the lips between 2000 and 2019 from the 17 registries of the USA were identified. Incidence and incidence-based mortality rates were analyzed using SEER*Stat 8.4.0.1 software. This paper calculated incidence rates and incidence-based mortality rates by 100,000 person-years for sex, age, race, SEER registries, median household income ($/year), rural-urban distribution, and primary site. The annual percent changes (APC) in incidence and incidence-based mortality rates were then calculated using joinpoint regression software. Results: Among 8,625 patients diagnosed with cSCC on the lips from 2000 to 2019, men (74.67%), white (95.21%), and 60-79 years old were the most common population, and 3,869 deaths from cSCC on the lips occurred. The overall incidence of cSCC on the lips was 0.516 per 100,000 person-years. cSCC on the lip incidence rates were highest among men, white, and patients aged 60-79 years old. cSCC on the lip incidence rates decreased by 3.210%/year over the study period. The incidence of cSCC on the lips has been decreasing in all sexes, ages, high- or low-income households, and urban or rural patients. The overall incidence-based mortality rate of cSCC on the lips during 2000-2019 was 0.235 per 100,000 person-years. cSCC on the lip incidence-based mortality rates were highest among men, whites, and people older than 80 years old. cSCC on the lip incidence-based mortality increased by 4.975%/year over the study period. cSCC on the lip incidence-based mortality rates increased for all sexes, races, ages, primary sites, high- or low-income households, and urban or rural patients during the study period. Conclusion: Among patients in the USA diagnosed with cSCC on the lips from 2000 to 2019, the overall incidence decreased by 3.210% annually, and incidence-based mortality increased by 4.975%/year. These findings update and supplement the epidemiological information of cSCC on the lips in the USA.

Stem Cell-Derived Exosomes: A New Method for Reversing Skin Aging.

Senescence is an inevitable natural life process that involves structural and functional degeneration of tissues and organs. Recently, the process of skin aging has attracted much attention. Determining a means to delay or even reverse skin aging has become a research hotspot in medical cosmetology and anti-aging. Dysfunction in the epidermis and fibroblasts and changes in the composition and content of the extracellular matrix are common pathophysiological manifestations of skin aging. Reactive oxygen species and matrix metalloproteinases play essential roles in this process. Stem cells are pluripotent cells that possess self-replication abilities and can differentiate into multiple functional cells under certain conditions. These cells also possess a strong ability to facilitate tissue repair and regeneration. Stem cell transplantation has the potential for application in anti-aging therapy. Increasing studies have demonstrated that stem cells perform functions through paracrine processes, particularly those involving exosomes. Exosomes are nano-vesicular substances secreted by stem cells that participate in cell-to-cell communication by transporting their contents into target cells. In this chapter, the biological characteristics of exosomes were reviewed, including their effects on extracellular matrix formation, epidermal cell function, fibroblast function and antioxidation. Exosomes derived from stem cells may provide a new means to reverse skin aging.

Adipose-Derived Stem Cell Exosomes Promoted Hair Regeneration.

BACKGROUND: Some scholars have found that dermal papilla spheroid-derived exosomes could promote the development of hair follicles. However, whether adipose-derived stem cell exosomes (ADSC-Exos) have a similar effect on hair growth has not been determined yet. Thus, the purpose of this article was to detect whether ADSC-Exos could promote hair regeneration. METHODS: Adipose-derived stem cells (ADSCs) were isolated from 6-week-old C57BL/6 mice. Then, ADSC-Exos were isolated from the ADSCs. Western blotting was used to detect specific exosome markers. The particle size and distribution of the exosomes were analyzed by NanoSight dynamic light scattering. A total of 12 nude mice were randomly divided into two groups (n = 6 each): the ADSC-Exos group and the control group. For the control group, a mixture of freshly isolated dermal cells (DCs) and epidermal cells (ECs) was grafted. For the ADSC-Exos group, a mixture of DCs, ECs, and 50 µg/ml of ADSC-Exos was grafted. Gross evaluation of the hair regeneration was carried out 2-3 weeks after the transplantation, and the graft site was harvested for histology at the third week. RESULTS: The existence of exosomes derived from ADSCs was evidenced by CD63, ALX1, and CD9 expression. Two or three weeks after the grafting, the number of regenerated hairs in the ADSC-Exos group was higher than that in the control group (p < 0.001). Histologically, the terminal hairs were remarkable in the ADSC-Exos group, whereas the hair follicles observed in the control group were comparatively immature. The ADSC-Exos group had a higher number of regenerated follicles than the control group (p < 0.001). In addition, we found that the skin tissues in the ADSC-Exos group had higher PDGF and vascular endothelial growth factor expressions and lower transforming growth factor beta 1 levels than those in the control group. CONCLUSION: Our results indicated that ADSC-Exos could promote in vivo hair follicle regeneration.

Antimicrobial Susceptibility, Biotypes and Phylotypes of Clinical Cutibacterium (Formerly Propionibacterium) acnes Strains Isolated from Acne Patients: An Observational Study.

INTRODUCTION: The aim of this study was to investigate the distribution of antimicrobial susceptibility, biotypes and phylotypes of clinical Cutibacterium acnes (C. acnes, formerly Propionibacterium acnes) isolates as well as the relationship among demographic factors, C. acnes biotypes and phylotypes. METHODS: Cutibacterium acnes was collected from the skin lesions of acne patients who visited the dermatologic department of Huashan Hospital in Shanghai from October 2016 to March 2017. The agar dilution method was conducted to determine the minimum inhibitory concentrations (MICs) of C. acnes, the fermentation test to identify biotypes and then multiplex touchdown polymerase chain reaction (PCR) to identify phylotypes. RESULTS: Of the 63 C. acnes strains we isolated, 18 (28.6%), 31 (49.2%) and 4 (6.3%) strains were resistant to clindamycin, erythromycin and moxifloxacin, respectively; no strains were resistant to tetracycline, minocycline, fusidic acid or ß-lactam, while metronidazole was completely resisted; 3 strains showed multidrug resistance (MDR). Biotype III (BIII) was the major biotype (50.8%) followed by BI and BV (both 15.9%), BII (12.7%) and lastly BIV (4.8%). IA1 was the predominant phylotype (71.4%) followed by IA2 (19.0%), II (4.8%), IB (3.2%) and IC (1.6%), while III was not detected. Significant differences were observed in the severity of disease: different degrees of acne severity reflected different biotype and phylotype distributions, and the biotype distribution of mild acne was different from that of moderate acne; the phylotype distribution of moderate acne varies from that of severe acne, too. Additionally, there was no significant difference in the distribution of biotypes or phylotypes between resistant and susceptible strains. CONCLUSION: Erythromycin and clindamycin resistances are the most common in clinical C. acnes strains; BIII is the predominant biotype and IA1 is the major phylotype of C. acnes, which are mainly related to disease severity.

Severe Cutaneous Adverse Reactions: A Single-Center Retrospective Study of 173 Patients in China.

BACKGROUND: Severe cutaneous adverse reactions (SCAR) to drugs are a crucial public health issue and the use of systemic corticosteroids in SCAR has been controversial. OBJECTIVE: To analyze clinical features, causative drugs, treatment, outcomes, and prognostic factors of SCAR in the case-series of 173 patients, and add more information to the debate of using systemic corticosteroids in SCAR management. METHODS: A retrospective study of 173 SCAR patients diagnosed with drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) at a tertiary care institution in China between January 2014 and December 2017 was conducted. RESULTS: Of 173 patients, allopurinol, carbamazepine, and antibiotics are the most frequently implicated drugs for DRESS (40.4%), SJS/TEN (26.0%), and AGEP (40.0%) respectively. Moreover, there is a strongly negative correlation between early corticosteroids use and the progression (p=0.000) and severity (p=0.01) of skin lesions. However, there is no association between early corticosteroids use and the mortality of SCAR (odds ratio: 1.01, 95% confidence interval: 0.95~1.08). In addition, lymphadenopathy, eosinophilia, and interval from onset to corticosteroids treatment were correlated with SCAR prognosis. CONCLUSION: Prompt short-course systemic corticosteroids use is associated with early-stage skin lesions remission without influencing the disease mortality. Lymphadenopathy and eosinophilia were the independent poor prognostic factors of SCAR.