|
1
|
Radwan SES, El-Moslemany RM, Mehanna RA, Thabet EH, Abdelfattah EZA, El-Kamel A. Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment. Drug Deliv 2022; 29:1150-1163. [PMID: 35384774 PMCID: PMC9004496 DOI: 10.1080/10717544.2022.2058648] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/18/2022] [Accepted: 03/21/2022] [Indexed: 02/08/2023] Open
Abstract
Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.
Collapse
|
|
2
|
Roshdy OH, Abdallah WI, Farid CI, Mehanna RA, Bayoumi NH, Ismail AI. Stromal vascular fraction improves the durability of autologous fat temple augmentation-A split-face randomized study using ultrasound biomicroscopy. J Plast Reconstr Aesthet Surg 2022; 75:1870-1877. [PMID: 35125305 DOI: 10.1016/j.bjps.2021.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 12/05/2021] [Accepted: 12/19/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Autologous lipotransfer aims to restore aging-associated volume loss, but with low predictability owing to 20-90% first-year loss of transferred fat. Enrichment by adipose-derived stem cells within the stromal vascular fraction (SVF) aims to improve volume retention through their differentiation potential and paracrine actions exerted by secreted trophic and angiogenic factors. Assessing studies lacked split-face designs, and used multitudes of enrichment ratios, preparation techniques and evaluation methods ending in contradictory reports regarding enrichment advantage. AIM To test whether enriching the autologous fat graft with SVF will increase its residual volume as compared to non-enriched graft. A standardized enrichment protocol and ratio and objective assessment were employed. PATIENTS AND METHODS In a split-face design, and after random assignment, bilateral temple augmentation using non-enriched versus SVF-enriched autologous lipotransfer were compared in middle-aged females otherwise healthy non-pregnant or breast-feeding females abstaining from esthetic or weight-controlling procedures. Temple volume scale (TVS), skin layers' thickness measured by ultrasound biomicroscopy (UBM), visual analog scale for patients' satisfaction, and side effects were blindly assessed at 1 week, 3 months, and 6 months. RESULTS In the included 15 females, TVS was significantly lower (0.5 ± 0.5 versus 1.1 ± 0.7, P = 0.0001), and% hypodermal augmentation was significantly higher (70.92 ± 58.09 versus 18.93 ± 19.33, P = 0.001) on the SVF-enriched side at 6 months. Patient satisfaction was similar bilaterally (P = 1), as were sequelae frequencies as lumping, edema, and ecchymosis. CONCLUSION SVF enrichment of transferred fat significantly improved its residual volume at 6 months; a conclusion that needs further validation. UBM was an informative objective tool for the following temple skin thickness changes. Trial registration clinical trials.gov (NCT03965936).
Collapse
|
|
3
|
Solaiman A, Mehanna RA, Meheissen GA, Elatrebi S, Said R, Elsokkary NH. Potential effect of amniotic fluid-derived stem cells on hyperoxia-induced pulmonary alveolar injury. Stem Cell Res Ther 2022; 13:145. [PMID: 35379329 PMCID: PMC8978174 DOI: 10.1186/s13287-022-02821-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Accepted: 03/20/2022] [Indexed: 02/08/2023] Open
Abstract
Background With the widespread of Coronavirus Disease 2019 pandemic, in spite of the newly emerging vaccines, mutated strains remain a great obstacle to supportive and preventive measures. Coronavirus 19 survivors continue to face great danger of contacting the disease again. As long as no specific treatment has yet to be approved, a great percentage of patients experience real complications, including among others, lung fibrosis. High oxygen inhalation especially for prolonged periods is per se destructive to the lungs. Nevertheless, oxygen remains the first line support for such patients. In the present study we aimed at investigating the role of amniotic fluid-mesenchymal stem cells in preventing versus treating the hyperoxia-induced lung fibrosis in rats. Methods The study was conducted on adult albino rats; 5 pregnant female rats were used as amniotic fluid donors, and 64 male rats were randomly divided into two groups: Control group; where 10 rats were kept in normal atmospheric air then sacrificed after 2 months, and hyperoxia-induced lung fibrosis group, where 54 rats were exposed to hyperoxia (100% oxygen for 6 h/day) in air-tight glass chambers for 1 month, then randomly divided into the following 5 subgroups: Hyperoxia group, cell-free media-treated group, stem cells-prophylactic group, stem cells-treated group and untreated group. Isolation, culture and proliferation of stem cells were done till passage 3. Pulmonary function tests, histological examination of lung tissue under light and electron microscopes, biochemical assessment of oxidative stress, IL-6 and Rho-A levels, and statistical analysis of data were performed. F-test (ANOVA) was used for normally distributed quantitative variables, to compare between more than two groups, and Post Hoc test (Tukey) for pairwise comparisons. Results Labelled amniotic fluid-mesenchymal stem cells homed to lung tissue. Stem cells administration in the stem cells-prophylactic group succeeded to maintain pulmonary functions near the normal values with no significant difference between their values and those of the control group. Moreover, histological examination of lung tissues showed that stem cells-prophylactic group were completely protected while stem cells-treated group still showed various degrees of tissue injury, namely; thickened interalveolar septa, atelectasis and interstitial pneumonia. Biochemical studies after stem cells injection also showed decreased levels of RhoA and IL-6 in the prophylactic group and to a lesser extent in the treated group, in addition to increased total antioxidant capacity and decreased malondialdehyde in the stem cells-injected groups. Conclusions Amniotic fluid-mesenchymal stem cells showed promising protective and therapeutic results against hyperoxia-induced lung fibrosis as evaluated physiologically, histologically and biochemically. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02821-3.
Collapse
|
|
4
|
Elsehly WM, Mourad GM, Mehanna RA, Kholief MA, El-Nikhely NA, Awaad AK, Attia MH. The potential implications of estrogenic and antioxidant-dependent activities of high doses of methyl paraben on MCF7 breast cancer cells. J Biochem Mol Toxicol 2022; 36:e23012. [PMID: 35174924 DOI: 10.1002/jbt.23012] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 11/05/2021] [Accepted: 01/05/2022] [Indexed: 02/05/2023]
Abstract
Methyl paraben (MP) is an endocrine-disrupting compound that possesses estrogenic properties and contributes to an aberrant burden of estrogen signaling in the human breast and subsequently increasing the risks for the development of breast cancer. The exact exposure, as well as the safe concentrations, are variable among daily products. The present study addresses the effects of exposure to escalated concentrations of MP on the proliferation of MCF-7 breast cancer cells in addition to exploring its other mechanisms of action. The study involved exposure of cultured MCF-7 breast cancer cells to seven MP concentrations, ranging from 40 to 800 µM for 5 days. Cell viability, apoptosis, and proliferation were respectively assessed using crystal violet test, flow cytometric analysis, and quantitative real-time polymerase chain reaction for Ki-67 expression. The estradiol (E2) secretion and oxidative stress were also assessed and analyzed in correlation to MP's proliferation and cytotoxicity potentials. The results showed that the maximum proliferative concentration of MP was 800 µM. At a concentration of 40 μM and higher, MP induced increased expression of Ki-67, denoting enhanced proliferation of the cells in monolayer culture. A positive correlation between the detrimental oxidative stress effect of MP's tested concentrations, cell proliferation, and viability was demonstrated (p < 0.05). Our results indicated that MP at high doses induced sustained cell proliferation due to E2 secretion as well as its antioxidant activity. Accordingly, it was concluded that high and unpredicted exposure to MP might carry a carcinogenic hazard on estrogen receptor-positive breast cancer cells.
Collapse
|
|
5
|
Mehanna RA, Essawy MM, Barkat MA, Awaad AK, Thabet EH, Hamed HA, Elkafrawy H, Khalil NA, Sallam A, Kholief MA, Ibrahim SS, Mourad GM. Cardiac stem cells: Current knowledge and future prospects. World J Stem Cells 2022; 14:1-40. [PMID: 35126826 PMCID: PMC8788183 DOI: 10.4252/wjsc.v14.i1.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 07/02/2021] [Accepted: 01/06/2022] [Indexed: 02/06/2023] Open
Abstract
Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs. Since the inception of the field several decades ago, regenerative medicine therapies, namely stem cells, have received significant attention in preclinical studies and clinical trials. Apart from their known potential for differentiation into the various body cells, stem cells enhance the organ's intrinsic regenerative capacity by altering its environment, whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration. Recently, research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells (CSCs/CPCs). The global burden of cardiovascular diseases’ morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy. This review will discuss the nature of each of the CSCs/CPCs, their environment, their interplay with other cells, and their metabolism. In addition, important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells. Moreover, the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration. Finally, the novel role of nanotechnology in cardiac regeneration will be explored.
Collapse
|
|
6
|
Extracellular cystine influences human preadipocyte differentiation and correlates with fat mass in healthy adults. Amino Acids 2021; 53:1623-1634. [PMID: 34519922 PMCID: PMC8521515 DOI: 10.1007/s00726-021-03071-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/19/2021] [Indexed: 02/08/2023]
Abstract
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.
Collapse
|
|
7
|
Etman SM, Mehanna RA, Bary AA, Elnaggar YSR, Abdallah OY. Undaria pinnatifida fucoidan nanoparticles loaded with quinacrine attenuate growth and metastasis of pancreatic cancer. Int J Biol Macromol 2021; 170:284-297. [PMID: 33340624 DOI: 10.1016/j.ijbiomac.2020.12.109] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 12/11/2020] [Accepted: 12/14/2020] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is a devastating gastrointestinal tumor with limited Chemotherapeutic options. Treatment is restricted by its poor vascularity and dense surrounding stroma. Quinacrine is a repositioned drug with an anticancer activity but suffers a limited ability to reach tumor cells. This could be enhanced using nanotechnology by the preparation of quinacrine-loaded Undaria pinnatifida fucoidan nanoparticles. The system exploited fucoidan as both a delivery system of natural origin and active targeting ligand. Lactoferrin was added as a second active targeting ligand. Single and dual-targeted particles prepared through nanoprecipitation and ionic interaction respectively were appraised. Both particles showed a size lower than 200 nm, entrapment efficiency of 80% and a pH-dependent release of the drug in the acidic environment of the tumor. The anticancer activity of quinacrine was enhanced by 5.7 folds in dual targeted particles compared to drug solution with a higher ability to inhibit migration and invasion of cancer. In vivo, these particles showed a 68% reduction in tumor volume compared to only 20% for drug solution. In addition, they showed a higher animals' survival rate with no hepatotoxicity. Hence, these particles could be an effective option for the eradication of pancreatic cancer cells.
Collapse
|
|
8
|
El-Habashy S, Eltaher H, Gaballah A, Mehanna R, El-Kamel AH. Biomaterial-Based Nanocomposite for Osteogenic Repurposing of Doxycycline. Int J Nanomedicine 2021; 16:1103-1126. [PMID: 33603371 PMCID: PMC7887185 DOI: 10.2147/ijn.s298297] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Accepted: 01/20/2021] [Indexed: 02/05/2023] Open
Abstract
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 23-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.
Collapse
|
|
9
|
El-Habashy SE, Eltaher HM, Gaballah A, Zaki EI, Mehanna RA, El-Kamel AH. Hybrid bioactive hydroxyapatite/polycaprolactone nanoparticles for enhanced osteogenesis. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 119:111599. [PMID: 33321643 DOI: 10.1016/j.msec.2020.111599] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/20/2020] [Accepted: 09/23/2020] [Indexed: 02/05/2023]
Abstract
Hydroxyapatite nanoparticles (HApN) are largely employed as osteogenic inorganic material. Inorganic/polymeric hybrid nanostructures can provide versatile bioactivity for superior osteogenicity, particularly as nanoparticles. Herein, we present hybrid biomaterial-based hydroxyapatite/polycaprolactone nanoparticles (HAp/PCL NPs) realized using simple preparation techniques to augment HApN osteogenicity. Using wet chemical precipitation, we optimized HApN crystalline properties utilizing a 23-factorial design. Optimized HApN exhibited typical Ca/P elemental ratio with high reaction yield. Surface area analysis revealed their mesoporous nature and high surface area. Hybrid HAp/PCL NPs prepared using direct emulsification-solvent evaporation maintained HApN crystallinity with no observed chemical interactions. To the best of our knowledge, we are the first to elaborate the biocompatibility and osteogenicity of nanoparticulate hybrid HAp/PCL. Hybrid HAp/PCL NPs outperformed HApN regarding mesenchymal cell proliferation and osteodifferentiation with reduction of possible cytotoxicity. Unlike HApN, hybrid HAp/PCL NPs presented moderate expression of early osteogenic markers, Runx-2 and osteopontin and significantly elevated expression of the late osteogenic marker, bone sialoprotein after 10-day culture. Our results indicate that hybrid bioactive HAp/PCL NPs could offer a more prominent osteogenic potential than plain HApN for bone regenerative applications as a standalone nanoplatform or as part of complex engineered systems.
Collapse
|
|
10
|
Zakaria DM, Zahran NM, Arafa SAA, Mehanna RA, Abdel-Moneim RA. Histological and Physiological Studies of the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Bleomycin Induced Lung Fibrosis in Adult Albino Rats. Tissue Eng Regen Med 2021; 18:127-141. [PMID: 33090319 PMCID: PMC7579902 DOI: 10.1007/s13770-020-00294-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 08/04/2020] [Accepted: 08/15/2020] [Indexed: 02/08/2023] Open
Abstract
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.
Collapse
|
|
11
|
Thabet E, Yusuf A, Abdelmonsif DA, Nabil I, Mourad G, Mehanna RA. Extracellular vesicles miRNA-21: a potential therapeutic tool in premature ovarian dysfunction. Mol Hum Reprod 2020; 26:906-919. [PMID: 33049041 DOI: 10.1093/molehr/gaaa068] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2020] [Revised: 09/15/2020] [Indexed: 02/06/2023] Open
Abstract
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 to the 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 (TFCs) 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.
Collapse
|
|
12
|
Abolgheit S, Abdelkader S, Aboushelib M, Omar E, Mehanna R. Bone marrow-derived mesenchymal stem cells and extracellular vesicles enriched collagen chitosan scaffold in skin wound healing (a rat model). J Biomater Appl 2020; 36:128-139. [PMID: 33019853 DOI: 10.1177/0885328220963920] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
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.
Collapse
|
|
13
|
Etman SM, Abdallah OY, Mehanna RA, Elnaggar YSR. Lactoferrin/Hyaluronic acid double-coated lignosulfonate nanoparticles of quinacrine as a controlled release biodegradable nanomedicine targeting pancreatic cancer. Int J Pharm 2020; 578:119097. [PMID: 32032904 DOI: 10.1016/j.ijpharm.2020.119097] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Revised: 01/27/2020] [Accepted: 01/28/2020] [Indexed: 02/07/2023]
Abstract
Quinacrine is an antimalarial drug that was repositioned for treatment of cancer. This is the first work to enhance quinacrine activity and minimize its associated hepatotoxicity via loading into bio-degradable, bio-renewable lignosulfonate nanoparticles. Particles were appraised for treatment of pancreatic cancer, one of the most life-threatening tumors with a five-year survival estimate. Optimum nanocomposites prepared by polyelectrolyte interaction exhibited a particle size of 138 nm, a negative surface charge (-28 mV) and a pH dependent release of the drug in an acidic environment. Ligands used for active targeting (lactoferrin and hyaluronic acid) were added to nanoparticles' surface via layer by layer coating technique. The highest anticancer activity on PANC-1 cells was demonstrated with dual active targeted particles (3-fold decrease in IC50) along with an increased ability to inhibit migration and invasion of pancreatic cancer cells. In vivo studies revealed that elaborated nanoparticles particles showed the highest tumor volume reduction with enhanced survival without any toxicity on major organs. In conclusion, the elaborated nanoparticles could be considered as a promising targeted nanotherapy for treatment of pancreatic cancer with higher efficacy& survival rate and lower organ toxicity.
Collapse
|
|
14
|
Omar AM, Meleis AE, Arfa SA, Zahran NM, Mehanna RA. Comparative Study of the Therapeutic Potential of Mesenchymal Stem Cells Derived from Adipose Tissue and Bone Marrow on Acute Myocardial Infarction Model. Oman Med J 2019; 34:534-543. [PMID: 31745418 PMCID: PMC6851069 DOI: 10.5001/omj.2019.97] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVES Stem cell therapy is a promising approach in the treatment of acute myocardial infarction (AMI). Mesenchymal stem cells (MSC) from bone marrow (BM-MSC) and adipose tissue (AT-MSC) are attractive and feasible for preclinical and clinical trials. In this study, we compared the therapeutic potential of BM-MSC and AT-MSC in repairing the hearts of rats with isoproterenol (ISO)-induced AMI. METHODS Forty-two female rats were assigned into two groups; the optimization and the experimental group. The optimization groups were further subdivided into control group and the AMI induced group (using ISO). The experimental group was subdivided into AMI+cell-free media injected in the tail vein, AMI+BM-MSC, and AMI+AT-MSC groups treated with the intravenous injection of their respective cell types. Twenty-eight days after induction, electrocardiogram (ECG) was performed, and heart tissue samples were collected for histological assessment and cells tracing. RESULTS MSC therapy repaired cardiac functions shown by the restoration of ST segment, QT and QRS intervals in the ECG when compared to the AMI group. Infarct area was significantly decreased, and cardiac tissue regeneration signs were shown on histopathological examination. CONCLUSIONS Both MSC sources proved to be equally efficient in the assessed parameters.
Collapse
|
|
15
|
Bone Marrow-Derived Mesenchymal Stem Cell Potential Regression of Dysplasia Associating Experimental Liver Fibrosis in Albino Rats. BIOMED RESEARCH INTERNATIONAL 2019; 2019:5376165. [PMID: 31781620 PMCID: PMC6874956 DOI: 10.1155/2019/5376165] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 09/25/2019] [Accepted: 10/08/2019] [Indexed: 02/07/2023]
Abstract
Objectives Assessing the therapeutic efficacy of superparamagnetic iron oxide nanoparticles (SPIO) labeled bone marrow-derived mesenchymal stem cells (BM-MSCs) on experimental liver fibrosis and associated dysplasia. Materials and Methods MSCs were obtained from 10 male Sprague-Dawley rats while 50 female rats were divided into control (CG), liver fibrosis (CCL4, intraperitoneal injection of CCl4 for 8 weeks), and CCL4 rats treated with SPIO-labeled MSCs (MSCs/CCl4) with and without continuing CCL4 injection for another 8 weeks. Assessment included liver histopathology, liver function tests, transmission electron microscopic tracing for homing of SPIO-MSCs, immunofluorescence histochemistry for fibrosis and dysplasia markers (transforming growth factor-beta (TGF-β1), proliferation nuclear antigen (PCNA), glypican 3)), and quantitative gene expression analysis for matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Results SPIO-labeled MSCs were engrafted in the fibrotic liver and the BM/MSCs demonstrated regression for fibrous tissue deposition and inhibition progression of dysplastic changes in the liver of CCl4-treated rats on both the histological and molecular levels. Conclusion BM-MSCs possess regenerative and antidysplastic potentials.
Collapse
|
|
16
|
Abou Eitta RS, Ismail AA, Abdelmaksoud RA, Ghezlan NA, Mehanna RA. Evaluation of autologous adipose-derived stem cells vs. fractional carbon dioxide laser in the treatment of post acne scars: a split-face study. Int J Dermatol 2019; 58:1212-1222. [PMID: 31297798 DOI: 10.1111/ijd.14567] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 05/22/2019] [Accepted: 06/07/2019] [Indexed: 02/05/2023]
Abstract
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.
Collapse
|
|
17
|
Mehanna RA, Nabil I, Attia N, Bary AA, Razek KA, Ahmed TAE, Elsayed F. The Effect of Bone Marrow-Derived Mesenchymal Stem Cells and Their Conditioned Media Topically Delivered in Fibrin Glue on Chronic Wound Healing in Rats. BIOMED RESEARCH INTERNATIONAL 2015; 2015:846062. [PMID: 26236740 PMCID: PMC4508387 DOI: 10.1155/2015/846062] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2015] [Revised: 06/17/2015] [Accepted: 06/18/2015] [Indexed: 02/05/2023]
Abstract
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.
Collapse
|
|
18
|
El Deeb NMF, Mehanna RA. Assessment of maturation status of tumor-infiltrating dendritic cells in invasive ductal carcinoma of the breast: relation with vascular endothelial growth factor expression. Turk Patoloji Derg 2014; 29:193-200. [PMID: 24022309 DOI: 10.5146/tjpath.2013.01186] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
OBJECTIVE Poor immunogenicity has been described in breast carcinoma although dendritic cells, the major antigen presenters, are known to infiltrate the tumor. Vascular endothelial growth factor has been proposed to reduce local immune response in tumors. We investigated the maturation status of dendritic cells in invasive ductal carcinoma of the breast in relation to vascular endothelial growth factor expression and clinicopathological parameters. MATERIAL AND METHOD Fifty invasive ductal carcinomas of the breast were immunostained with CD1a (marker of immature dendritic cells); CD83 (marker of mature dendritic cells), vascular endothelial growth factor, estrogen receptor and progesterone receptor. RESULTS Mature dendritic cells were detected in 36 cases (72%), and correlated with smaller tumor size, negative lymph nodes, positive steroid receptor status, and lower grade (P < 0.001). Immature dendritic cells were found in 100% of cases and correlated only with negative steroid receptor expression (estrogen receptor and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial growth factor expression was detected in 44 cases (88%), and correlated directly with positive nodal metastases (P=0.014), correlated inversely with mature dendritic cell count (P=0.005); and did not correlate with immature dendritic cell count (P=0.104). CONCLUSION Mature dendritic cell count correlates with good prognostic features in invasive ductal carcinoma of the breast, suggesting their role in initiating primary anti-tumor immune response. Vascular endothelial growth factor expression may play a role in inhibition of dendritic cell maturation sequence in the tumor microenvironment.
Collapse
|
|
19
|
Sobhy M, Sadaka M, Okasha N, Farag ES, Saleh A, Ismail H, El Seteiha M, Ragy H, Hameed MA, Mehanna R. Stent for Life Initiative placed at the forefront in Egypt 2011. EUROINTERVENTION 2012; 8 Suppl P:P108-15. [PMID: 22917780 DOI: 10.4244/eijv8spa19] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
|