Background Scarring is a distressing outcome of acne, as it causes cosmetic and psychological problems to the patients. Unfortunately no single treatment is satisfactory; instead, employing multiple modalities may have better outcome. Autologous adipose tissue‐derived adult stem cells (AT‐ASCs) and their secretory factors can stimulate collagen synthesis; angiogenesis and migration of fibroblasts thus regenerate damaged tissues. Also, conventional treatments for acne scarring, such as lasers and topical regimens, induce new collagen synthesis via activation of dermal fibroblasts or growth factors. The aim of the study was to verify the effectiveness of AT‐ASCs for the treatment of acne scarring vs. the fractional carbon dioxide laser (FxCR). Subjects and methods Split face comparative study included 10 adult patients with post‐acne scars on both sides of the face. One side received AT‐ASCs single injection while the other received three sessions of FxCR. Scars were then assessed using the global scoring system Goodman and Baron, scar area percent using NIH ImageJ software and functional assessment by measuring the transepidermal water loss (TEWL) and skin hydration. Both sides were followed for three months. Results A significant improvement in the degree of scar severity, scar area percent, skin hydration, and TEWL after 3 months of treatment on both sides of the face with insignificant differences between both treatment modalities, provided that AT‐ASCs treatment was employed once vs. three sessions of FxCR. Conclusion One injection of AT‐ASCs is as effective as three sessions of FxCR in the treatment of atrophic acne scars.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) represent a modern approach for management of chronic skin injuries. In this work, we describe BM-MSCs application versus their conditioned media (CM) when delivered topically admixed with fibrin glue to enhance the healing of chronic excisional wounds in rats. Fifty-two adult male rats were classified into four groups after induction of large-sized full-thickness skin wound: control group (CG), fibrin only group (FG), fibrin + MSCs group (FG + SCs), and fibrin + CM group (FG + CM). Healing wounds were evaluated functionally and microscopically. Eight days after injury, number of CD68+ macrophages infiltrating granulation tissue was considerably higher in the latter two groups. Although—later—none of the groups depicted a substantially different healing rate, the quality of regenerated skin was significantly boosted by the application of either BM-MSCs or their CM both (1) structurally as demonstrated by the obviously increased mean area percent of collagen fibers in Masson's trichrome-stained skin biopsies and (2) functionally as supported by the interestingly improved epidermal barrier as well as dermal tensile strength. Thus, we conclude that topically applied BM-MSCs and their CM—via fibrin vehicle—could effectively improve the quality of healed skin in chronic excisional wounds in rats, albeit without true acceleration of wound closure.

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Plasma cysteine is associated with human obesity, but it is unknown whether this is mediated by reduced, disulfide (cystine and mixed-disulfides) or protein-bound (bCys) fractions. We investigated which cysteine fractions are associated with adiposity in vivo and if a relevant fraction influences human adipogenesis in vitro. In the current study, plasma cysteine fractions were correlated with body fat mass in 35 adults. Strong positive correlations with fat mass were observed for cystine and mixed disulfides (r ≥ 0.61, P < 0.001), but not the quantitatively major form, bCys. Primary human preadipocytes were differentiated in media containing cystine concentrations varying from 10–50 μM, a range similar to that in plasma. Increasing extracellular cystine (10–50 μM) enhanced mRNA expression of PPARG2 (to sixfold), PPARG1, PLIN1, SCD1 and CDO1 (P = 0.042– < 0.001). Adipocyte lipid accumulation and lipid-droplet size showed dose-dependent increases from lowest to highest cystine concentrations (P < 0.001), and the malonedialdehyde/total antioxidant capacity increased, suggesting increased oxidative stress. In conclusion, increased cystine concentrations, within the physiological range, are positively associated with both fat mass in healthy adults and human adipogenic differentiation in vitro. The potential role of cystine as a modifiable factor regulating human adipocyte turnover and metabolism deserves further study.

Background Over the past ten years, regenerative medicine has focused on the regeneration and the reconstruction of damaged, diseased, or lost tissues and organs. Skin, being the largest organ in the human body, had attained a good attraction in this field. Delayed wound healing is one of the most challenging clinical medicine complications. This study aimed to evaluate the collagen chitosan scaffold’s effect alone, or enriched with either bone marrow-derived mesenchymal stem cells (BM-MSCs) or their secreted extracellular vesicles (EVs) on the duration and quality of skin wound healing. Methods A full-thickness skin wound was induced on the back of 32 adult male Sprague-Dawley rats. The wounds were either covered with collagen chitosan scaffolds alone, scaffolds enriched with stem cells, or extracellular vesicles. Unprotected wounds were used as control. Healing duration, collagen deposition and alignment, CD 68+ macrophage count, and functional tensile strength of healed skin were assessed (α = 0.05, n = 8). Results The rate of skin healing was significantly accelerated in all treated groups compared to the control. Immuno-histochemical assessment of CD68+ macrophages showed enhanced macrophages count, in addition to higher collagen deposition and better collagen alignment in EVs and BM-MSCs treated groups compared to the control group. Higher tensile strength values reflected the better collagen deposition and alignment for these groups. EVs showed higher amounts of collagen deposition and better alignment compared to MSCs treated group. Conclusion The collagen chitosan scaffolds enriched with MSCs or their EVs improved wound healing and improved the quantity and remodeling of collagen with a better assignment to EVs.

Chemotherapy induces an irreversible premature ovarian dysfunction (POD). Amniotic fluid mesenchymal stem cells (AFMSCs) can rescue fertility; however, the notion that stem cells can rejuvenate follicles is highly controversial due tthe predetermined ovarian reserve. This study aims to isolate AFMSC-derived extracellular vesicles (EVs) and investigate their abundancy for the anti-apoptotic miRNA-21 as a means of ovarian restoration. Female rats were divided into healthy controls and POD-induced groups. The POD induced groups were subdivided into three groups according to the therapies they received: placebo-treated POD, AFMSC and EVs groups. Rats were assessed for serum anti-Müllerian hormone (AMH) levels, ovarian caspase 3 and PTEN protein levels in the ovarian lysate. Total follicular counts (TFC) were estimated from stained ovarian sections. Functional recovery was investigated through daily vaginal smears and mating trials. In-vitro chemical transfection of the AFMSCs with selective miRNA-21 mimics/inhibitors followed by isolation of EVs for therapy was conducted in two additional groups. At the interval points studied, treatment with AFMSCs and EVs equally restored TFC, AMH levels, regular estrous cycles and fruitful conception, while it both diminished caspase 3 and PTEN levels. EVs carrying miRNA-21 mimics recapitulated the short-term effects. Placebo-treated POD or EVs carrying miRNA-21 inhibitors showed augmented ovarian follicular damage demonstrated the low AMH levels, TFC and high levels of PTEN and caspase 3. miRNA-21 allowed regeneration by modulating PTEN and caspase 3 apoptotic pathways. Our findings exemplify that EVs could serve as an innovative cell-free therapeutic tool functioning through their miRNA content and that miRNA-21 has a chief regenerative role through modulating PTEN and caspase 3 apoptotic pathways.

Background: Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats. Methods: 30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson’s trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung. Results: Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions. Conclusion: MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis. Electronic supplementary material The online version of this article (10.1007/s13770-020-00294-0) contains supplementary material, which is available to authorized users.

Background Besides its antimicrobial action, doxycycline (DX) has lately been repurposed as a small-molecule drug for osteogenic purposes. However, osteogenic DX application is impeded by its dose-dependent cytotoxicity. Further, high-dose DX impairs cell differentiation and mineralization. Purpose Integrating DX into a biomaterial-based delivery system that can control its release would not only ameliorate its cytotoxic actions but also augment its osteogenic activity. In this work, we managed to engineer novel composite DX–hydroxyapatite–polycaprolactone nanoparticles (DX/HAp/PCL) to modify DX osteogenic potential. Methods Employing a 2 3 -factorial design, we first optimized HApN for surface-area attributes to maximize DX loading. Composite DX/HAp/PCL were then realized using a simple emulsification technique, characterized using various in vitro methods, and evaluated for in vitro osteogenesis. Results The developed HApN exhibited a favorable crystalline structure, Ca:P elemental ratio (1.67), mesoporous nature, and large surface area. DX/HAp/PCL achieved the highest reported entrapment efficiency (94.77%±1.23%) of DX in PCL-based particles. The developed composite system achieved controlled release of the water-soluble DX over 24 days. Moreover, the novel composite nanosystem managed to significantly ameliorate DX cytotoxicity on bone-marrow stem cells, as well as enhance its overall proliferation potential. Alkaline phosphatase and mineralization assays revealed superior osteodifferentiation potential of the composite system. Quantification of gene expression demonstrated that while DX solution was able to drive bone-marrow stem cells down the osteogenic lineage into immature osteoblasts after 10-day culture, the innovative composite system allowed maturation of osteodifferentiated cells. To the best of our knowledge, this is the first work to elaborate the impact of DX on the expression of osteogenic genes: RUNX2 , OSP, and BSP. Further, the osteogenicity of a DX-loaded particulate-delivery system has not been previously investigated. Conclusion Our findings indicate that repurposing low-dose DX in complementary biomaterial-based nanosystems can offer a prominent osteogenic candidate for bone-regeneration purposes.