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.

Objectives Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc. Methods The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model. Results TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo. Conclusion TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc.

干细胞源性外泌体(stem cell-derived exosome)是由干细胞分泌的无细胞囊泡,他们携带多种功能性蛋白质和遗传信息,在细胞间通讯中发挥着关键作用.此外,干细胞源性外泌体在细胞迁移、肿瘤侵袭、组织再生、损伤后心肌修复和骨折愈合等方面的研究也被广泛报道.目前,大量研究表明干细胞源性外泌体通过调节皮肤生理和病理功能在伤口愈合、皮肤老化和瘢痕形成等方面发挥着重要作用,提示干细胞源性外泌体在美容皮肤病学中具有重要的发展潜力.现就干细胞源性外泌体在美容皮肤病学中的研究进展作一综述.

外泌体是一种微小的膜性囊泡结构,是脂肪来源干细胞旁分泌的重要组成部分,可将信息物质传递至细胞或组织从而参与机体各种生物学过程,并在清除废弃物质、介导细胞信息传递、肿瘤治疗以及组织修复再生等方面发挥重要作用.外泌体可为毛发再生提供一种新型治疗策略.现就脂肪来源干细胞外泌体(exosomes from adipose-derived stem cells,ADSC-Exos)的相关生物特征作一综述,分析脱发产生的发病机理及其相关治疗措施,并对临床中使用外泌体治疗脱发及其毛发再生可能涉及的相关机制进行阐述.

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-β1 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-β1/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-β1/Smad signaling pathway to inhibit the TGF-β1-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.

遗传性大疱性表皮松解症(EB)是一种罕见的残毁型、致死型单基因遗传性皮肤病,对社会和家庭造成了沉重负担.细胞疗法因其卓越稳定的临床疗效成为EB治疗中极有前景的一种手段,本文从干细胞和体细胞两方面总结近年来细胞疗法在EB的实验室研究及临床应用方面的进展.

ObjectiveThis 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.MethodsPatients 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.ResultsAmong 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.ConclusionAmong 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.

With the development of science and technology, nanomaterials, especially superparamagnetic iron oxide nanoparticles (SPIONs), aroused great interests of researcher due to their special performance. SPIONs below 10 nm had good superparamagnetism, excellent magnetic field response which widely applied in biomedical field. Researchers had developed a variety of methods for synthesizing SPIONs. However, nanoscale magnetic materials tended to agglomerate and oxidized due to their high surface energy and high surface metal chemical activity; as a result, the magnetic properties and dispersibility of the SPIONs were reduced. Moreover, naked SPIONs possessed poor biocompatibility. Hence, it was necessary for surface modification of SPIONs in practical applications. In fact, SPIONs were usually surface coated by various materials to maintain their properties including non-polymeric organic stabilizers, polymeric stabilizers, and inorganic molecules. SPIONs had good dispersibility and biocompatibility after surface treatment. To date, SPIONs had been widely used in biomedical fields including magnetron therapy, magnetic hyperthermia, MRI, biological separation, and catalysis. Neurological conditions were the second leading cause of death globally, accounting for 9 million deaths per year. With increasing life stress, the increasing incidence of brain diseases imposes a severe economic burden on society and families. SPIONs owned excellent magnetism which responded superiorly to magnetic fields. In the presence of an external magnetic field, the magnetic nanoparticles are controlled by the magnetic field. More and more attention was fixed on SPIONs in nervous system. In review, recent advances of SPIONs and its applications in neuroscience under external magnetic field were included.

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.

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. 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. 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. Our results indicated that ADSC-Exos could promote in vivo hair follicle regeneration.

骨关节炎(OA)是一种好发于中老年人的慢性关节疾病,临床主要表现为关节肿痛、僵硬和活动受限等,是致残的重要原因之一.基质血管组分(SVF)是脂肪组织除去成熟脂肪细胞等成分后的一种异质性细胞群,其中的间充质干细胞赋予SVF干细胞特性,其他多种细胞组分也具有调节机体免疫、促进组织重建等作用.通过对OA的流行病学、发病机制、诊断和治疗,以及SVF治疗OA的临床研究和其治疗机制进行综述,以期为SVF对OA的临床治疗研究提供参考.

Diabetic foot is one of the severest complications of diabetes. In severe cases, this disease may be lead to amputation or even death due to secondary infection and ischemic necrosis. Since the ineffectiveness of traditional therapy, autologous stem cell transplantation has been used to treat diabetic foot. This simple, safe, and effective therapy is expected to be applied and promoted in the future. In this review, we described the detailed pathogenesis of diabetic foot and the common clinical treatments currently used. We also revealed vascular remodeling as the potential mechanism of therapeutic functions of adipose-derived stromal vascular fraction (SVF) in treating diabetic foot.