Alyaa Ragaei Hassan Mohamed Mostafa

RababHassan, Dina Sabry

01/10/2019

OBJECTIVE: To elucidate the effect of Alzheimer's disease on the structure of circumvallate papilla taste buds and the possible role of exosomes on the taste buds in Alzheimer's disease. DESIGN: Forty two ovariectomized female adult albino rats were utilized and divided into: Group I: received vehicle. Group II: received aluminum chloride to induce Alzheimer's disease. Group III: after the induction of Alzheimer's disease, each rat received single dose of exosomes then left for 4 weeks. The circumvallate papillae were prepared for examination by light and transmission electron microscope. STATISTICAL ANALYSIS: histomorphometric data were statistically analyzed. RESULTS: Histological examination of circumvallate papilla in Group I showed normal histological features. Group II revealed distorted features. Group III illustrated nearly normal histological features of circumvallate. Silver impregnation results showed apparently great number of heavily impregnated glossopharyngeal nerve fibers in both Groups I & III but markedly decreased in Group II. Synaptophysin-immunoreactivity was strong in Group I, mild in Group II and moderate in Group III. The ultra-structural examination of taste bud cells revealed normal features in Group I, distorted features in Group II and almost normal features in Group III. Statistically highest mean of Synaptophysin-immunoreactivity area% was for Group I, followed by Group III, and the least value was for Group II. CONCLUSIONS: Alzheimer's disease has degenerative effects. Bone marrow mesenchymal stem cell (BM-MSC)-derived exosomes have the ability to improve the destructive changes induced by Alzheimer's disease.

Alyaa Ragaei Hassan Mohamed Mostafa

A Safwat, D Sabry, E Amer, RH Mahmoud, RM Shamardan

01/10/2018

This study aimed to evaluate the effect of mesenchymal stem cells (MSCs)–derived exosomes in retina regeneration of experimentally induced diabetes mellitus (DM) in a rabbit model. Exosomes are extracellular vesicles that contain many microRNAs (micRNAs), mRNAs, and proteins from their cells of origin. DM was induced by intravenous (IV) injection of streptozotocin in rabbits. MSCs were isolated from adipose tissue of rabbits. Exosomes were extracted from MSCs by ultracentrifugation. Exosomes were injected by different routes (IV, subconjunctival (SC), and intraocular (IO)). Evaluation of the treatment was carried out by histopathological examination of retinal tissues and assessment of micRNA-222 expression level in retinal tissue by real-time polymerase chain reaction. Histologically, by 12 weeks following SC exosomal treatment, the cellular components of the retina were organized in well-defined layers, while IO exosomal injection showed well-defined retinal layers which were obviously similar to layers of the normal retina. However, the retina appeared after IV exosomal injection as irregular ganglionic layer with increased thickness. MicRNA-222 expression level was significantly reduced in diabetic controls when compared to each of healthy controls and other diabetic groups Adipose mesenchymal stem cells–derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits A Safwat, D Sabry, [...], and RM Shamardan Additional article information Abstract This study aimed to evaluate the effect of mesenchymal stem cells (MSCs)–derived exosomes in retina regeneration of experimentally induced diabetes mellitus (DM) in a rabbit model. Exosomes are extracellular vesicles that contain many microRNAs (micRNAs), mRNAs, and proteins from their cells of origin. DM was induced by intravenous (IV) injection of streptozotocin in rabbits. MSCs were isolated from adipose tissue of rabbits. Exosomes were extracted from MSCs by ultracentrifugation. Exosomes were injected by different routes (IV, subconjunctival (SC), and intraocular (IO)). Evaluation of the treatment was carried out by histopathological examination of retinal tissues and assessment of micRNA-222 expression level in retinal tissue by real-time polymerase chain reaction. Histologically, by 12 weeks following SC exosomal treatment, the cellular components of the retina were organized in well-defined layers, while IO exosomal injection showed well-defined retinal layers which were obviously similar to layers of the normal retina. However, the retina appeared after IV exosomal injection as irregular ganglionic layer with increased thickness. MicRNA-222 expression level was significantly reduced in diabetic controls when compared to each of healthy controls and other diabetic groups with IV, SC, and IO routes of injected exosomes (0.06 ± 0.02 vs. 0.51 ± 0.07, 0.28 ± 0.08, 0.48 ± 0.06, and 0.42 ± 0.11, respectively). We detected a significant negative correlation between serum glucose and retinal tissue micRNA-222 expression level (r = −0.749, p = 0.001). We can associate the increased expression of micRNA-222 with regenerative changes of retina following administration of MSCs-derived exosomes. The study demonstrates the potency of rabbit adipose tissue–derived MSCs exosomes in retinal repair. So, exosomes are considered as novel therapeutic vectors in MSCs-based therapy through its role in shuttling of many factors including micRNA-222.

Alyaa Ragaei Hassan Mohamed Mostafa

Hala El- Menoufy

01/06/2016

Background Gingival overgrowth (GO) is usually associated with multiple factors including immunosuppressive agents as cyclosporine (CsA) and Tacrolimus (TAC), and hereditary gingival fibromatosis (HGF). Objective To compare the expression of TGF-β1, PDGF, TIMP-1 and MMP-9 at the molecular and cellular levels in patients receiving (CsA or TAC) and patients manifested (HGF), to cast some light on the pathogenic mechanism potentially involved in the collagen (COL) turnover of both conditions. Subjects and methods: Gingival tissue samples were obtained from patients undergoing therapy with CsA (n = 6), TAC (n = 6), HGF (n = 3) as well as control tissues from systemically healthy control (n = 6). Tissue sections were immune-stained by labeled streptavidin-biotin (DAB) technique, using monoclonal antibodies against TGF-β1, PDGF-β, TIMP-1 and MMP-9. Results: comparison of type of expression among the studied groups, showed significant diffuse expression of TGF-β1 and PDGF-β in group I and II with P value = 0.58 and 0.38 respectively. The expression of MMP-9 was significantly diffuse in TAC or CsA group when compared to HGF group with P value = 0.38, mean while there was a significant diffuse expression of TIMP-1 in HGF group when compared to TAC or CsA group with P value = 0.38. Conclusions In conclusion the biological mechanisms behind the drug induced gingival overgrowth (DIGO) and HGF is targeting COL turnover but in different ways. Also, this may explain the need for periodic surgical correction of the gingival form and architecture in HGF cases, unlike the DIGO which can be overcame by replacement of CsA by TAC with improvement of oral health.

Alyaa Ragaei Hassan Mohamed Mostafa

Aisha Mansy, Dina Sabry

01/11/2015

The present study was performed to evaluate the influence of MSCs and / or vitamin E on chemically induced hepatocellular carcinoma (HCC) in male albino rats model. We also aimed to assess IHC staining by Arginase 1 as an early histological marker for HCC. Methods: Eighty five male albino rats were included in the study and were divided into control and hepato-cellular carcinoma induced groups: Group 1 (Control group):20 rats received normal balanced diet and 3 ml/kg body weight castor oil twice weekly for 5 month. Animals were scarified 2, 3, 4 and 5 month [5 rats at each scarification]. Hepatocellular Carcinoma induced groups: 65 rats received a single intraperitoneal dose of diethyl nitrosamine (DENA) at a dose of 200 mg/kg body weight followed by twice weekly subcutaneous injections of carbon tetra chloride (CCl4) at a dose of 3 ml/kg body weight. Five rats of that group were scarified after 2 months; blood samples and liver specimen were collected to assess the induction of HCC. The remaining 60 rats were further classified into: Group 2 (HCC untreated group): 15 rats received DENA and CCl4 as previous and left as model untreated control for the rest of the experimental duration. Group 3 (HCC/MSCs treated group): 15 rats received DENA and CCl4 as previous, followed by injected with 107 human amniotic-MSCs (h-AMSCs)/rat intravenously (through tail vein). Group 4 (HCC/vitamin E treated group): 15 rats received DENA and CCl4 as previous, followed by oral administration of 10 mg/kg α-tocopherol acetate( Vit E) dissolved in 2ml/kg body weight castor oil daily. Group 5 (HCC/MSCs &vitamin E treated group): 15 rats received (DENA) and CCL4 as previous, followed by injection of 107human amniotic-MSCs (h-AMSCs)/rat intravenously (through tail vein) & oral administration of 10 mg/kg body weight α-tocopherol, (Vit E) dissolved in 2ml/kg body weight castor oil daily. Five animals from each group were scarified after (3,4and 5 month) post HCC induction. Both Histological and immunohistochemical examination of liver tissue were done, and serum levels of albumin and α-fetoprotein were estimated in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-CCl4 only revealed presence of anaplastic carcinoma, focal nodular hyperplasia with large and small cells atypia. While HCC rats treated with both (h-AMSCs) and Vit E (α-tocopherol) has shown improvement of histopathological picture in relation to that of human amniotic-MSCs group and Vitamin E group used alone, in the form of attenuation of the tumor size with minimal hepatic cell damage. Positive Arginase-1 IHC reaction was observed in HCC group with the decrease in it reactivity in all other groups it became absolutely reduced to neoplastic cells only in both (h-AMSCs) group and Vit E only

Alyaa Ragaei Hassan Mohamed Mostafa

Neilly Hamouda

01/07/2015

Objectives:The aim of this study is to report the effect of equine demineralized bone matrix (DBM) on the healing of oral cystic cavities following enucleation using clinical parameters. Study design:Twelve patients aged from 20 to 40 years and suffering from cystic lesion in the jaw were included in this study. Cystic cavity augmentation with DBM was performed on 6 patients. After an average of 6 months’ healing period, a core bone was obtained and stained for histologic analysis simultaneously with implant placement. Results:Uneventful healing and spontaneous filling of the residual cavities was obtained in all cases. All implants showed favorable Osseointegration, and final restorations were completed without failure in all cases. Histologically, new bone formation was active around grafted bone, and grafted bone was well integrated to the newly formed bone matrix. In histomorphometric analysis, vital bone volume was 25.2 ±11.9%. Conclusion:The equine DBM is clinically useful for the increase of bone volume in cystic cavities after enucleation, because of its favorable effect of new bone formation and it is considered to be a safe, simple, reliable, acceptable, and easy handling bone grafting material. Keywords: Demineralized bone matrix; Bone graft; Oral cyst

Alyaa Ragaei Hassan Mohamed Mostafa

Hala El- Menoufy, Laila Ahmed Rashed, Dina Sabry

01/11/2014

Objectives: Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. Methods & Results: Oral ulcers were induced by topical application for formocresol in the oral cavity of dogs Transplantation of undifferentiated GFP-labeled Autologous Bone Marrow Stem Cell (BMSCs), Adipose Derived Stem Cell (ADSCs) or vehicle (saline) was injected around the ulcer in each group. The healing process of the ulcer was monitored clinically and histopathlogically. Gene expression of vascular endothelial growth factor (VEGF) was detected in MSCs by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Expression of VEGF and collagen genes was detected in biopsies from all ulcers. Results: MSCs expressed mRNA for VEGF MSCs transplantation significantly accelerated oral ulcer healing compared with controls. There was increased expression of both collagen and VEGF genes in MSCs – treated ulcers compared to controls. Conclusions: MSCs transplantation may help to accelerate oral ulcer healing, possibly through the induction of angiogenesis by VEGF together with increased intracellular matrix formation as detected by increased collagen gene expression. This body of work has provided evidence supporting clinical applications of adipose-derived cells in safety and efficacy trials as an alternative for bone marrow mesenchymal stem cells in oral ulcer healing.

Alyaa Ragaei Hassan Mohamed Mostafa

Hala El-Menoufy, Hesham S Sadeq, Dina Sabry

01/04/2014

Bone marrow mesenchymal stem cells (BMSCs) are the key to regenerative wound healing. MSCs have spatial memory and respond to local environment. The goal of this study was to evaluate the use of systemic and intralesional transplantation of BMSCs for regeneration of oral mucosa in an in vivo dog model. Materials and Methods: Transplantation of undifferentiated green fluorescent protein (GFP)-labeled autologous BMSCs systemically, submucosally or vehicle (saline) was injected around the chemically induced oral ulcer in each group of 18 adult dogs. The healing process of the ulcer was monitored clinically and histopathologically. Gene expression of vascular endothelial growth factor (VEGF) and collagen genes was detected in biopsies from all ulcers. One way ANOVA was used to compare between means of the three groups. Results were considered significant at P< 0.05.

Alyaa Ragaei Hassan Mohamed Mostafa

01/01/2014

Alyaa Ragaei Hassan Mohamed Mostafa

01/07/2013

The aim of the present study was to compare osteogenic potential of bone marrow- derived mesenchymal stem cells (BMSCs) and adipose tissue – derived mesenchymal stem cells (ASCs) on the healing process of induced bone defect in the tibia of irradiated albino rats. Forty five male albino rats were subjected to whole body 6 gray gamma radiation. One day post irradiation, a unicortical osseous wound was created. The rats were randomly equally divided into three groups. Group 1 (irradiated), group 2 and group 3 (BMSCs & ASCs were delivered into the holes respectively). Animals were sacrificed after 3.6 and 12 weeks postoperative. The healing process was assessed radiographically (measuring the bone density) and histopathologically. The bone density decreased in all groups after the third week and slightly increased after the sixth one. After the twelfth week, newly formed bone densities of BMSCs group followed by ASCs group exceeded the density of the bone at 0 week (density of the bone at the base of the defect) that represents lamellar bone filling the defect. Histopathologically, the newly formed bone trabeculae in group 2 appeared thick entrapping vascular bone narrow and were surrounded by regularly arranged deeply stained osteoblasts. BMSCs application showed better healing process than that of ASCs which showed thinner woven bone trabeculae. The bone marrow cavities slightly increased in size but still smaller than those were detected in irradiated group. In conclusion, topical engraftment of BMSCs accelerated the healing process of the induced bone defect more than in case of ASCs application.

Alyaa Ragaei Hassan Mohamed Mostafa

Mehanni SS, Ibrahim NF, Rahed LA

01/05/2013

BACKGROUND AND OBJECTIVES: Irradiated wound healing is a highly complex and dynamic process. The latest technology making a huge difference in this process is stem cell therapy. The goal of this study was to evaluate the use of bone marrow-derived mesenchymal stem cells (BM-MSCs) or human amniotic epithelial cells (HAECs) in the healing of irradiated wounds. METHODS AND RESULTS: Forty five male albino rats were subjected to whole body 6 gray gamma radiations. One day post irradiation, full-thickness incisional wound was created in the tibial skin. The rats were randomly equally divided into three groups. The incisions of the first group (gp I) were injected intra-dermally with saline before stitching and those of both the second (gp II) and the third groups (gp III) were intradermally injected with BM-MSCs and HAECs before stitching respectively. Animals were sacrificed after the third, seventh and fourteenth days postoperative. The healing process was assessed histopathologically. CXCL-5, SDF-1 and Transforming growth factor-beta 1 (TGF-β1) expression were also detected in biopsies from all wounds. Expression of TGF-β1 in gp I was more than the other groups leading to severe inflammation, deficient healed dermis and delayed reepithelialization. SDF-1 expression was high in gp II while CXCL-5 expression was high in gp III causing accelerated wound healing. BM-MSCs showed a great effect on the quality of the dermis, while superiority of the epithelium and its appendages were achieved in HAECs group. CONCLUSIONS: Using BM-MSCs and HAECs could be used safely in case of irradiated wounds

Alyaa Ragaei Hassan Mohamed Mostafa

Samah S. Mehanni, Noha F. Ibrahim, Laila A. Rashed

01/05/2013

Alyaa Ragaei Hassan Mohamed Mostafa

Dalia Abdel-Hameed El-Baz, Samah S Mehanni, Eman M El- Maghraby

01/06/2012

This study was held to clarify changes in the epithelium of the fungiform papillae after irradiation at the microscopic level as well as the effect of grape seed oil (GSO) on these changes and the changes in the innervation of these papillae. Thirty five male Swiss Albino rats were included in this study. The animals were divided into, Grape seed irradiated group (GSI gp): GSO was administrated orally in accompanied with radiation. Irradiated group (IR gp): The same protocol was applied to this group except that the animals received distilled water instead. Control group(C gp): only distilled water was administrated orally. The right tongue halves were prepared for Ultrastructural studies. The left halves were used for detection of the innervations using S100. Degeneration of the cell nuclei and organelles in stratum basale and spinosum of the fungiform papillae in IR gp was obvious. In the GSI gp the nuclei had prominent nucleoli and granulated chromatin. The regeneration of the epithelium in the IR gp was delayed compared with GSI gp. Regeneration of the cytoskeleton was advanced in the GSI gp. Significant obvious decrease in the innervations was indicated in the IR gp at the third day post irradiation compared with both GSI gp and C gp. Toward the end of the experiment, increase in the innervations was more detectable in GSI gp. For these reasons, grape seed oil is recommended to be consumed as a dietary supplement and could be useful in synergizing the hazardous of radiation on the tongue papillae. (Samah S Mehanni, Eman M El- Maghraby, Alyaa R Hassan, and Dalia A H El-Baz. The Ameliorative Role of Grape Seed Oil on Irradiated Rat Fungiform Papillae. Journal of American Science.

Alyaa Ragaei Hassan Mohamed Mostafa

Samah S Mehanni, Eman M El- Maghraby, Dalia A H El-Baz

01/01/2012

This study was held to clarify changes in the epithelium of the fungiform papillae after irradiation at the microscopic level as well as the effect of grape seed oil (GSO) on these changes and the changes in the innervation of these papillae. Thirty five male Swiss Albino rats were included in this study. The animals were divided into, Grape seed irradiated group (GSI gp): GSO was administrated orally in accompanied with radiation. Irradiated group (IR gp): The same protocol was applied to this group except that the animals received distilled water instead. Control group(C gp): only distilled water was administrated orally. The right tongue halves were prepared for Ultrastructural studies. The left halves were used for detection of the innervations using S100. Degeneration of the cell nuclei and organelles in stratum basale and spinosum of the fungiform papillae in IR gp was obvious. In the GSI gp the nuclei had prominent nucleoli and granulated chromatin. The regeneration of the epithelium in the IR gp was delayed compared with GSI gp. Regeneration of the cytoskeleton was advanced in the GSI gp. Significant obvious decrease in the innervations was indicated in the IR gp at the third day post irradiation compared with both GSI gp and C gp. Toward the end of the experiment, increase in the innervations was more detectable in GSI gp. For these reasons, grape seed oil is recommended to be consumed as a dietary supplement and could be useful in synergizing the hazardous of radiation on the tongue papillae.

Alyaa Ragaei Hassan Mohamed Mostafa

Hala El- Menoufy, Laila Ahmed Rashed, Dina Sabry, Amal Hassan, Nagwa Roshdy, Hazem Atta

01/07/2011

Background and Objectives: Autogenous bone grafts is considered to be the best choice for reconstructive surgery. Adipose Derived Stromal Cells (ASCs) represents a promising tool for new clinical concepts in supporting cellular therapy. The goal of our study was to investigate bone regeneration following application of autologous ASCs with or without Platelet-Rich Plasma (PRP) at dehiscence-type defects in alveolar bone in dogs. Methods and Results: Standardized buccal dehiscence defects (4× 3×3 mm) were surgically created in eighteen dogs, the defects were grafted with either ASCs -PRP, ASCs alone, or without grafting material. Three months later; a bone core was harvested from grafted and non grafted sites for histological, histochemical and histomorphometric assessment. There was no evidence of inflammation or adverse tissue reaction with either treatment. Defects grafted with ASCs-PRP showed a significantly higher result (p≤ 0.05), with a mean area % of spongy bone and compact bone of (64.96±5.37 and 837.62±24.95), compared to ASCs alone (47.65±1.43 and 661.92±12.65) and without grafting (33.55± 1.74 and 290.85±7.27) respectively. The area % of lamellated bone increased significantly reaching its highest level in group A followed by group B. Also a significant increase in area % of neutral mucopolysaccharides and calcified reactivity of Masson|s Trichrome stain in groups A and B compared to group C was obtained. Conclusions: Our results suggest that, the addition of PRP to ASCs enhances bone formation after 3 months and may be clinically effective in accelerating postsurgical healing in both periodontal and maxillofacial surgical applications.

Alyaa Ragaei Hassan Mohamed Mostafa

01/01/2011

Alyaa Ragaei Hassan Mohamed Mostafa

Amaal Tohamy, Hala El menoufy, Mahmoud Elmeteni, Amr Abdelaal, Khaled Mahmoud Makboul

01/06/2010