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Abstract Background Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. Results In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. Conclusions Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. Video Abstract

Background: Exosomes are small extracellular vesicles that play important roles in intercellular communication and have potential therapeutic applications in regenerative medicine. Dermal mesenchymal stem cells (DMSCs) are a promising source of exosomes due to their regenerative and immunomodulatory properties. However, the molecular mechanisms regulating exosome secretion from DMSCs are not fully understood. Results: In this study, the role of peroxiredoxin II (Prx II) in regulating exosome secretion from DMSCs and the underlying molecular mechanisms were investigated. It was discovered that depletion of Prx II led to a significant reduction in exosome secretion from DMSCs and an increase in the number of intracellular multivesicular bodies (MVBs), which serve as precursors of exosomes. Mechanistically, Prx II regulates the ISGylation switch that controls MVB degradation and impairs exosome secretion. Specifically, Prx II depletion decreased JNK activity, reduced the expression of the transcription inhibitor Foxo1, and promoted miR-221 expression. Increased miR-221 expression inhibited the STAT signaling pathway, thus downregulating the expression of ISGylation-related genes involved in MVB degradation. Together, these results identify Prx II as a critical regulator of exosome secretion from DMSCs through the ISGylation signaling pathway. Conclusions: Our findings provide important insights into the molecular mechanisms regulating exosome secretion from DMSCs and highlight the critical role of Prx II in controlling the ISGylation switch that regulates DMSC-exosome secretion. This study has significant implications for developing new therapeutic strategies in regenerative medicine. -6AE1Qxi5fhihA5_M9L54L Video Abstract [ABSTRACT FROM AUTHOR]

Dermis-isolated adult stem (DIAS) cells, abundantly available, are attractive for regenerative medicine. Strategies have been devised to isolate and to chondroinduce DIAS cells from various animals. This study aimed to characterize DIAS cells from human abdominal skin (human dermis-isolated adult stem [hDIAS] cells) and to compare and to refine various chondroinduction regimens to form functional neocartilage constructs. The stemness of hDIAS cells was verified (Phase I), three chondroinduction pretreatments were compared (Phase II), and, from these, one regimen was carried forward for refinement in Phase III for improving the mechanical properties of hDIAS cell-derived constructs. Multilineage differentiation and mesenchymal stem cell markers were observed. Among various chondroinduction pretreatments, the nodule formation pretreatment yielded constructs at least 72% larger in diameter, with higher glycosaminoglycan (GAG) content by 44%, compared with other pretreatments. Furthermore, it was found that culturing cells on nontissue culture-treated surfaces yielded constructs (1) on par with constructs derived from aggrecan-coated surfaces and (2) with superior mechanical properties than constructs derived from cells cultured on tissue culture-treated surfaces. After the nodule formation pretreatment, combined supplementation of TGF-β1, IGF-I, and fetal bovine serum significantly enhanced aggregate modulus and shear modulus by 75% and 69%, respectively, over the supplementation by TGF-β1 alone. In summary, human skin-derived DIAS cells are responsive to chondroinduction for forming neocartilage. Furthermore, the mechanical properties of the resultant human constructs can be improved by treatments shown to be efficacious in animal models. Advances made toward tissue-engineering cartilage using animal cells were shown to be applicable to hDIAS cells for cartilage repair and regeneration.

Objective: To investigate the therapeutic effects of total glucosides of paeony (TGP) on psoriasis based on the immunomodulatory effect of dermal mesenchymal stem cells (DMSCs). Methods: A total of 30 male BALB/c mice were divided into 6 groups (n=5 in each) by a random number table method, including control, psoriasis model (model, 5% imiquimod cream 42 mg/d), low-, medium- and high-dose TGP (50, 100, and 200 mg/kg, L, M-, and H-TGP, respectively), and positive control group (2.5 mg/kg acitretin). After 14 days of continuous administration, the skin's histopathological changes, apoptosis, secretion of inflammatory cytokines, and proportion of regulatory T cells (Treg) and T helper cell 17 (Th17) were evaluated using hematoxylin-eosin (HE) staining, TdT-mediated dUTP nick end labeling staining, enzyme-linked immunosorbent assay, and flow cytometry, respectively. DMSCs were further isolated from the skin tissues of normal and psoriatic mice, and the cell morphology, phenotype, and cycle were observed. Furthermore, TGP was used to treat psoriatic DMSCs to analyze the effects on the DMSCs immune regulation. Results: TGP alleviated skin pathological injury, reduced epidermis layer thickness, inhibited apoptosis, and regulated the secretion of inflammatory cytokines and the proportion of Treg and Th17 in the skin tissues of psoriatic mice (P<0.05 or P<0.01). There was no significant difference in cell morphology and phenotype between control and psoriatic DMSCs (P>0.05), however, more psoriatic DMSCs remained in G0/G1 phase compared with the normal DMSCs (P<0.01). TGP treatment of psoriatic DMSCs significantly increased cell viability, decreased apoptosis, relieved inflammatory response, and inhibited the expression of toll-like receptor 4 and P65 (P<0.05 or P<0.01). Conclusion: TGP may exert a good therapeutic effect on psoriasis by regulating the immune imbalance of DMSCs. [ABSTRACT FROM AUTHOR]

Aihong Peng,1 Funa Lu,1 Jianxiao Xing,1 Yu Dou,1 Yuanjun Yao,1 Juan Li,1 Junqin Li,1 Ruixia Hou,1 Kaiming Zhang,2 Guohua Yin1 1Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital, Taiyuan, People’s Republic of ChinaCorrespondence: Guohua Yin, Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5, Dong San Dao Xiang, Jiefang Road, Taiyuan, People’s Republic of China, Tel +86-0351-5656080, Email yinguohua1999@sina.comPurpose: Our recent studies found a splice region mutation in C3 accompanied by a significantly increased C3 in psoriatic peripheral blood. Mesenchymal stem cells (MSCs) are a key immunological suppression cell. We further investigate the regulation of MSCs on C3 in psoriasis.Patients and Methods: We analyzed the C3 and its upstream S100A9, S100A8 and downstream MCP1 in psoriatic and control skin, and in normal human epidermal keratinocytes (NHEKs) co-cultured with psoriatic versus control dermal-derived mesenchymal stem cells (DMSCs) by mRNA, iTRAQ (isobaric tags for relative and absolute quantitative) and simple Western analysis.Results: The mRNA and Simple Western analysis showed that the expression of C3, S100A8 and S100A9 are upregulated in psoriatic lesion (C3: mRNA, 9.23-fold, p = 0.0092; protein, 3.56-fold, p = 0.0244. S100A8: mRNA, 28.35-fold, p = 0.0015; protein, 4.68-fold, p = 0.0215. S100A9: mRNA, 79.45-fold, p = 0.0066; protein, 12.42-fold, p > 0.05). Moreover, the iTRAQ showed that C3 and S100A9 were significantly increased in NHEKs after co-cultured with psoriatic DMSCs compared to that of control DMSCs (C3: 3.40-fold, p = 0, FDR = 0; S100A9: 2.30-fold, p = 9.86E-241, FDR = 6.50E-239), verified by Simple Western. However, the expression of S100A8 and MCP1 was slightly different between the two groups.Conclusion: Our results suggest that psoriatic DMSCs contribute to the increased C3 expression in psoriatic lesion via upregulating S100A9, providing the theoretical basis for the role of C3 and DMSCs in the pathogenesis of psoriasis.Keywords: psoriasis, dermal mesenchymal stem cells, keratinocytes, C3, S100A9

Multiple methodologies have been reported to facilitate skin-derived precursor (SKP) growth, but the impact of plating density on SKP growth has not been studied. To determine the optimal plating density, we used six plating densities and two types of flasks for mouse SKP (mSKP) culture. On the 14th day, the number, diameter, and viability of mSKP spheres were compared by morphological assessment and cell counting kit 8, and we found the optimal plating density was 2.5 × 105–5 × 105 cells/mL. In addition, we investigated the correlation between the SKP spheres and the adherent cell colonies in the serum-free culture system. We treated the adherent cell colonies with two culture conditions and characterized the cells generated from two conditions by immunocytochemistry and induced differentiation, respectively. The results elucidated that the adherent cell colonies differentiated into either mSKPs or dermal mesenchymal stem cells under appropriate culture conditions. In conclusion, mSKP spheres differentiated from the adherent cell colonies. The optimal plating density significantly promoted and advanced the proliferation of adherent cell colonies, which optimized mSKP growth and yield. The adherent cell colonies possessed the capacity of differentiating into different types of cells under appropriate culture conditions.

One of the earliest events in the development of psoriatic lesion is a vascular network expansion. The abnormal vascular network is associated with increased endothelial cells (ECs) survival, proliferation, adhesion, migration, angiogenesis and permeability in psoriatic lesion. Our previous study demonstrated that epidermal growth factor‐like repeats and discoidin I‐like domains 3 (EDIL3) derived from psoriatic dermal mesenchymal stem cells (DMSCs) promoted cell–cell adhesion, migration and angiogenesis of ECs, but the molecular mechanism of upstream or downstream has not been explored. So, this study aimed to explore the association between EDIL3 derived from DMSCs (DMSCs‐derived EDIL3) and psoriasis‐associated angiogenesis. We injected recombinant EDIL3 protein to mouse model of psoriasis to confirm the roles of EDIL3 in psoriasis. Besides, we employed both short‐interference RNA (si‐RNA) and lentiviral vectors to explore the molecular mechanism of EDIL3 promoting angiogenesis in psoriasis. In vivo, this research found that after injected recombination EDIL3 protein, the epidermis thickness and microvessel density were both elevated. EDIL3 accelerated the process of psoriasis in the IMQ‐induced psoriasis‐like mouse model. Additionally, we confirmed that in vitro DMSCs‐derived EDIL3 is involved in the tube formation of ECs via αvβ3‐FAK/MEK/ERK signal pathway. This suggested that DMSCs‐derived EDIL3 and αvβ3‐FAK/MEK/ERK signal pathway in ECs play an important role in the pathogenesis of psoriasis. And the modification of DMSCs, EDIL3 and αvβ3‐FAK/MEK/ERK signal pathway will provide a valuable therapeutic target to control the angiogenesis in psoriasis. [ABSTRACT FROM AUTHOR]

Background: Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation and abnormal differentiation of keratinocytes. Dermal mesenchymal stem cells (DMSCs) are not only involved in the regeneration of skin tissue, but also can regulate skin microenvironment by secreting cytokines. However, whether and how psoriatic DMSCs regulate proliferation and differentiation of keratinocytes remains unknown. Objective: To study the effects of psoriatic DMSCs on the proliferation, differentiation, and migration of keratinocytes and the underlying mechanisms. Methods: Following co-cultures of HaCaT cells with either psoriatic DMSCs (p-DMSCs) or DMSCs from normal volunteers (n-DMSCs), HaCaT cell proliferation was assessed using CCK-8 and EDU incorporation assay, while scratch assay and transwell assay were used to assess cell migration. qRT-PCR was used to determine expression levels of mRNA for cell proliferation (Ki-67) and differentiation (keratin 5, involucrin, and filaggrin). Western blot was used to measure expression levels of proteins associated with keratinocyte proliferation and differentiation in cultured HaCaT cells treated with or without PI3K inhibitor. ELISA assay was used to measure expression profile of stem cell factor (SCF), epidermal growth factor (EGF), and interleukin-11 (IL-11) within the co-culture supernatants. Results: The results showed that p-DMSCs displayed a higher potency than n-DMSCs in stimulating proliferation, differentiation, and migration of HaCaT cells. Expression levels of PI3K and AKT proteins were markedly increased in HaCaT cells co-cultured with DMSCs versus HaCaT cell culture alone. Moreover, inhibition of the PI3K/AKT signaling pathway reversed the effect of p-DMSCs on proliferation, differentiation, and migration of HaCaT cells. Compared with n-DMSCs, the p-DMSCs showed increased secretion of IL-11, EGF, and SCF. Conclusion: p-DMSCs stimulate HaCaT cell proliferation, differentiation and migration via activating the PI3K/AKT signaling pathway, providing a new insight into the pathogenesis of psoriasis. [ABSTRACT FROM AUTHOR]

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer. [ABSTRACT FROM AUTHOR]

Although it is known that psoriatic dermal-derived mesenchymal stem cells (DMSCs) dysregulate keratinocyte proliferation, the biological activity profile of keratinocytes influenced by psoriatic DMSCs remain unknown. In the present study, we assessed the impact of psoriatic DMSCs on keratinocyte proliferation, differentiation, and glucose metabolism in normal human epidermal keratinocytes co-cultured with or without psoriatic DMSCs. Co-culture of normal human epidermal keratinocytes with psoriatic DMSCs downregulated expression levels of proteins associated with cell junction assembly (alpha-actinin-1, catenin beta-1, poliovirus receptor-related protein 4 and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2), while upregulating proteins associated with keratinocyte proliferation and differentiation (involucrin, isoform 2 of Histone-binding protein, isoform 3 of Telomeric repeat-binding factor 2 and keratin 13). Moreover, co-culture of normal human epidermal keratinocytes with psoriatic DMSCs stimulated keratinocyte proliferation and glycolysis, but reduced keratinocyte junctions. Taken together, these results demonstrate that psoriatic DMSCs increase keratinocyte proliferation and glycolysis, and reduce cell junctions, suggesting a pathogenic role of psoriatic DMSCs in epidermal hyperplasia, aberrant differentiation, and reduction in turnover time of keratinocytes in psoriasis.

In this study, we used RNA sequencing (RNA-seq) to analyze and compare bulk cell samples from wild-type (WT) dermal mesenchymal stem cells (DMSCs) (n = 3) and Prx II knockout DMSCs (n = 3). The purpose of the study was to elucidate the role of Prx II on allogeneic immune rejection of transplanted DMSCs. The results revealed differential expression of 472 genes (176 up-regulated and 296 down-regulated; p ≤ 0.05) between the PrxII+/+ (WT) and PrxII−/− sample groups. When highly regulated genes were categorized according to the Gene Ontology (GO) molecular function classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the PrxII−/− samples showed a robust downward trend in allograft rejection. The study identified 43 all immunologically rejected differentially expressed genes, of which 41 showed lower expression in the PrxII−/− vs. PrxII+/+ (WT) samples. These findings suggest that Prx II gene knockout may down-regulate the allograft rejection that occurs during DMSCs transplantation and improve the survival rate of DMSCs in the host. This study provides a new perspective on the clinical treatment of stem cell transplantation. [ABSTRACT FROM AUTHOR]

Our previous research implied mouse skin-derived precursors (mSKPs) possessed the capacity of anti-ultraviolet B (UVB) irradiation damage, and the mechanisms might be associated with transforming growth factor-β (TGF-β) signaling pathway activation. In this study, we investigated and compared the response to UVB irradiation between mSKPs and dermal mesenchymal stem cells (dMSCs), and explored the underlying mechanisms. Irradiation damage such as decreased cell viability, cell senescence, and cell death was observed in both mSKPs and dMSCs at 24 h after UVB exposure. In mSKPs, change in cell morphology, viability, cell senescence and death at the following time points implied the recovery of UVB irradiation damage. Additionally, thrombospondin1 (TSP1) and TGF-β1 increased significantly in mSKPs' supernatant after UVB irradiation. The gene expression of TSP1, TGF-β1, metalloproteinase 1 (MMP1), and Collagen I elevated shortly after the UVB exposure. The protein expression of TSP1, TGF-β1, MMP1, Collagen I, smad2/3, and p-smad2/3 at multiple time points after the UVB exposure was consistent with the gene expression results. In dMSCs, no obvious recovery was noticed. Together, these results revealed that in mSKPs, one of the mechanisms to attenuate the UVB irradiation damage might be the early activation of TGF-β/Smad pathway by TSP1. Given that mSKPs could differentiate into fibroblast-like SKP-derived fibroblasts (SFBs) in vivo or with the presence of serum, mSKPs might serve as a therapeutic potential for fibroblasts supplement and UVB irradiation damage treatment. Abbreviations: SKPs: skin-derived precursors; mSKPs: mouse SKPs; UVB: ultraviolet B; TGF-β/Smad: transforming growth factor-β/Smad; TSP1: thrombospondin 1; MMP 13: metalloproteinases 13; TβRII: TGF-β receptor II; SFBs: SKP-derived fibroblasts; KEGG: Kyoto encyclopedia of genes and genomes; DEGs: differentially expressed genes; dMSCs: dermal mesenchymal stem cells; LM: light microscope; CCK-8: cell counting kit 8; ELISA: Enzyme-linked immuno sorbent assay; qRT-PCR: quantitative real-time polymerase chain reaction; TSPs: thrombospondins; ECM: extracellular matrix; R-smads: receptor-regulated smads [ABSTRACT FROM AUTHOR]

Background: Available options for correction of facial volume loss, such as synthetic fillers, autologous fat and cultured fibroblasts, have limitations viz. temporary effect and high cost.Aim: To assess the use of a novel technique, autologous non-cultured dermal cell suspension transplantation, for correction of localized facial volume loss due to inflammatory pathologies.Methods: It was a pilot study conducted in the Dermatology Outpatient Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Autologous non-cultured dermal cell suspension was transplanted in a total of 10 patients, out of which 5 had predominantly dermal loss and the rest had predominantly lipoatrophy. The donor tissue from the gluteal region was digested into a single cell suspension using collagenase-1 and injected into the recipient area. The outcome was assessed subjectively by patients and investigators and objectively using ultrasonography. Cell count, viability testing and measurement of mesenchymal stem cells were also done.Results: On assessment of patients, the median improvement in the predominantly dermal atrophy group at 3 and 6 months was 70% (range: 10-90%) and 80% (range: 0-90%), respectively, and in the predominantly lipoatrophy group, 0% (range: 0-40) and 0% (range: 0-50), respectively. Mean thickness of dermis + subcutis at the baseline was 1.835 mm (range: 0.89-6.04 mm), which increased to 2.912 mm (range: 0.88-7.07 mm, P = 0.03) at 6 months.Limitations: Our pilot study has some limitations such as small sample size and heterogeneity of the recruited patients.Conclusions: Autologous non-cultured dermal cell suspension transplantation appears to be safe and effective in localized facial dermal defects because of inflammatory pathologies, but not effective in deeper defects. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are used for tissue regeneration in several pathological conditions, including autoimmune diseases. However, the optimal sources and culture requirements for these cells are still under investigation. Here, we compared mRNA expression in dermal MSCs (DMSCs) at passage (P) 3 and P5 to provide a reference for future studies related to DMSCs expansion. In normal DMSCs, the expression of three of eight genes associated with basic cellular activity were different at P5 compared to that at P3: PLCB4 and SYTL2 were upregulated by 4.30- and 6.42-fold, respectively (P < 0.05), whereas SATB2 was downregulated by 39.25-fold (P < 0.05). At the same time, genes associated with proliferation, differentiation, inflammation, and apoptosis were expressed at similar levels at P3 and P5 (P > 0.05). In contrast, in DMSCs isolated from psoriatic patients we observed differential expression of three inflammation-associated genes at P5 compared to P3; thus IL6, IL8, and CXCL6 mRNA levels were upregulated by 16.02-, 31.15-, and 15.04-fold, respectively. Our results indicate that normal and psoriatic DMSCs showed different expression patterns for genes related to inflammation and basic cell activity at P3 and P5, whereas those for genes linked to proliferation, differentiation, and apoptosis were mostly similar. [ABSTRACT FROM AUTHOR]

Objective: We characterized mRNA expression profiles in normal and psoriatic human dermal mesenchymal stem cells (DMSCs) to provide a reference for future investigation of differential gene expression in DMSCs. Results: Microarray and RNA sequencing (RNA-Seq) analyses both identified 23 differentially expressed genes using both platforms. The results showed comparable upregulation or downregulation for 14/23 genes using either platform and a 100 % coincidence rate was found by real-time PCR. For all of the differentially expressed genes that were verified by real-time PCR, the coincidence rate for RNA-Seq and real-time PCR was significantly higher than that for microarray analysis and real-time PCR (83.3 vs. 37.5 %, P < 0.0001). Furthermore, RNA-Seq revealed the presence of over 2300 novel transcription tags. Conclusion: Relative to microarray analysis, RNA-Seq is more accurate in identifying differentially expressed genes in DMSCs. [ABSTRACT FROM AUTHOR]

To investigate the regulation of psoriatic dermal mesenchymal stem cells (p-DMSCs) in the expression of vascular growth factor (VEGF), and migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. A co-culture model of HUVECs and dermal mesenchymal stem cells (DMSCs)was used in this study. After 7-day co-culture, changes in expression levels of VEGF mRNA and protein in HUVECs were assessed using RT-PCR and Western Blotting, respectively. Migration and tubular formation of HUVECs were also assessed following co-culture of DMSCs and HUVECs. In comparison to either HUVECs alone or co-culture of n-DMSCs and HUVECs, co-culture of HUVECs and p-DMSCs significantly increased expression levels of both VEGF mRNA (p < 0.01 vs. HUVECs alone) and protein in HUVECs (p < 0.001 vs. both HUVECs alone and HUVECs co-cultured with n-DMSCs). Moreover, p-DMSCs stimulated HUVEC migration and vascular formation (p < 0.05 vs. both HUVECs alone and co-culture of n-DMSCs and HUVECs). Psoriatic DMSCs can upregulate VEGF expression, and stimulate migration and angiogenesis of HUVECs, suggesting a pathogenic role of p-DMSCs in psoriasis. [Display omitted] • To the best of our knowledge this is the first report on the co-culture of p-DMSCs and HUVECs • The effect of pDMSCs on HUVECs was studied, which provided the basis for the pathogenesis of psoriasis • p-DMSCs affect the expression of VEGF through p38 MAPK, thereby affecting HUVECs migration and angiogenesis [ABSTRACT FROM AUTHOR]

The dermal mesenchymal stem cells (DMSCs) from psoriasis display higher expression level of epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3), while EDIL3 can bind integrins, including αvβ3 and αvβ5, to regulate angiogenesis. To assess the role of EDIL3 derived from DMSCs of psoriasis (P-DMSCs) in angiogenesis, in vitro, EDIL3 of DMSCs from psoriasis was silenced by interfering EDIL3. Then the efficacy of silencing EDIL3 was tested by fluorescent flag, qRT-PCR and western blotting. And, in vitro, the relationship of EDIL3 in DMSCs with the angiogenesis of HUVECs were investigated through co-culture system. In vivo, EDIL3 recombinant protein was injected into IMQ cream-induced psoriasis-like skin lesions of mouse and EDIL3-associated tube formation were determined using Image J software. Our results showed the capacity of the adhesion, migration and tube formation of HUVECs in all psoriatic DMSCs groups were significantly higher compared with the control and si-EDIL3 groups (all P <0.05) in vitro. Moreover, under stimulated by EDIL3 recombinant protein, EDIL3-associated tube formation was dramatically elevated in vivo (P <0.01). In this study, EDIL3 could promote the adhesion, migration and tube formation of ECs and participant in the angiogenesis pathogenesis of psoriasis through affecting biological function on ECs both in vitro and in vivo. The results suggest a potential role of the critical pro-angiogenic factor EDIL3 in psoriasis therapy. • EDIL3 was highly expressed in dermal mesenchymal stem cells (DMSCs) from psoriasis. • In vitro, DMSCs of psoriasis promote the proliferation, adhesion, migration and tube formation of endothelial cells (ECs). • In vivo, dermal microvessels density was dramatically elevated stimulated by EDIL3. • EDIL3 could participant in the angiogenesis pathogenesis of psoriasis through affecting biological function on ECs. [ABSTRACT FROM AUTHOR]

Peroxiredoxin II (Prx II) is involved in proliferation, differentiation, and aging in various cell types. However, Prx II-mediated stem cell regulation is poorly understood. Here, dermal mesenchymal stem cells (DMSCs), cell-growth factor-rich conditioned medium from DMSCs (DMSC-CM), and DMSC-derived exosomes (DMSC-Exos) were used to explore the regulatory role of Prx II in DMSC wound healing. Following treatment, wound healing was significantly decelerated in Prx II -/- DMSCs than in Prx II +/+ DMSCs. In vitro stimulation with 10 μM H 2 O 2 significantly increased apoptosis in Prx II -/- DMSCs compared with Prx II +/+ DMSCs. The mRNA expression levels of EGF, b-FGF, PDGF-B, and VEGF did not significantly differ between Prx II -/- and Prx II +/+ DMSCs. Fibroblasts proliferated comparably when treated with Prx II +/+ DMSC-CM or Prx II -/- DMSC-CM. Wound healing was significantly higher in the Prx II -/- DMSC-Exos-treated group than in the Prx II +/+ DMSCs-Exos-treated group. Moreover, microRNA (miR)-21-5p expression levels were lower and miR-221 levels were higher in Prx II -/- DMSCs than in Prx II +/+ DMSCs. Therefore, our results indicate that Prx II accelerated wound healing by protecting DMSCs from reactive oxygen species-induced apoptosis; however, Prx II did not regulate cell/growth factor secretion. Prx II potentially regulates exosome functions via miR-21-5p and miR-221.

Both skin-derived precursors (SKPs) and dermal mesenchymal stem cells (dMSCs) are promising candidates for cellular therapy and regenerative medicine. To date the comparison of phenotypes and transcriptomes of mouse SKPs (mSKPs) and dMSCs has never been reported. Here we characterized and compared the biological properties and transcriptomes of mSKP and dMSCs from the same mouse dermis sample. Firstly, we analyzed mSKPs and dMSCs by use of immunocytochemistry, cell cycle analysis, and CD antigen expression. Then we conducted the osteogenic, adipogenic, and chondrogenic induced differentiation for both cell types. Lastly, we compared their genomic profiles by RNA-sequencing (RNA-Seq), and verified the results of RNA-Seq by quantitative real time reverse transcription PCR (qRT-PCR). The results suggested that mSKPs and dMSCs shared similarities in certain positive stem cells markers expression, but demonstrated difference in Nanog and Oct4 expression. mSKPs and dMSCs demonstrated similar cell cycle distribution and CD antigen expression. Both types of cells could be induced differentiated into osteocytes, adipocytes, and chondrocytes. However, RNA-Seq and qRT-PCR results indicated that mSKPs and dMSCs had distinct transcriptome profiles. The majority of enriched differentially expressed genes (DEGs) from mSKPs was immune-related, while the majority of enriched DEGs from dMSCs was differentiation/development/disease-related. Transcriptome profiles suggested that mSKPs and dMSCs might have potential usage in the relevant morbidity management. These results may indicate a molecular basis for novel stem cell-based therapeutic strategies., (Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Human Limbal (L-MSCs) and Dermal Mesenchymal Stem Cell (D-MSCs) possess many properties that increase their therapeutic potential in ophthalmology and dermatology. It is known that purinergic signaling plays a role in many aspects of mesenchymal stem cells physiology. They release and respond to purinergic ligands, altering proliferation, migration, differentiation, and apoptosis. Therefore, more information on these processes would be crucial for establishing future clinical applications using their differentiation potential, but without undesirable side effects. This study evaluated and compared the expression of ecto-nucleotidases, the enzymatic activity of degradation of extracellular nucleotides and the metabolism of extracellular ATP in D-MSCs and L-MSCs, isolated from discard tissues of human skin and sclerocorneal rims. The D-MSCs and L-MSCs showed a differentiation potential into osteogenic, adipogenic, and chondrogenic lineages and the expression of markers CD105 + , CD44 + , CD14 - , CD34 - , CD45 - , as expected. Both cells hydrolyzed low levels of extracellular ATP and high levels of AMP, leading to adenosine accumulation that can regulate inflammation and tissue repair. These cells expressed mRNA for ENTPD1, 2, 3, 5 and 6, and CD73 that corresponded to the observed enzymatic activities. Thus, considering the degradation of ATP and adenosine production, limbal MSCs are very similar to dermal MSCs, indicating that from the aspect of extracellular nucleotide metabolism L-MSCs are very similar to the characterized D-MSCs. J. Cell. Biochem. 118: 2430-2442, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)