BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) have been shown to ameliorate cisplatin-induced acute kidney injury (AKI). The present study compares the efficacy of different routes of MSCs administration on kidney damage and regeneration after cisplatin-induced AKI. METHODS: A single intraperitoneal injection of cisplatin (5 mg/kg) was used to induce AKI in 160 rats. MSCs (5×106) were given by either intravenous, intra-arterial or kidney sub capsular injection one day after cisplatin injection. Suitable control groups were included. Rats were sacrificed at 4, 7, 11 and 30 days after cisplatin injection. Kidney function parameters, kidney tissue oxidative stress markers, and scoring for renal tissue injury, regeneration and chronicity were all determined. RESULTS: MSCs by any routes were able to ameliorate kidney function deterioration and renal tissue damage induced by cisplatin. The overall results of the three routes were equal. Differences between the different routes in one parameter were transient and inconsistent with other parameters. CONCLUSION: Changing the route of MSCs injection does not have a major influence on the outcome. Future evaluation should focus on differences between the routes of administration considering the long term safety.
Acute Kidney Injury* ; Animals ; Cisplatin ; Injections, Intraperitoneal ; Kidney ; Mesenchymal Stromal Cells* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley* ; Regeneration

Mesenchymal stem cells (MSCs) offer significant promise as a multipotent source for cell-based therapies and could form the basis for the differentiation and cultivation of tissue grafts to replace damaged tissue. However, no gene expression follow up analysis has been undertaken to characterize the in vitro adipogenic differentiated MSCs. The main goal of this study was to focus on MSCs and to analyze their differentiation capacity. To achieve this aim, bone marrow MSCs from sprague dawely rats were isolated, expanded in monolayer culture and characterized with respect to their cluster of differentiation (CD) and ability for adipogenic differentiation capacity. The expression of CD44, CD45, CD29, CD34, and CD90 on bone marrow derived MSCs was characterized using flow cytometry. Adipogenesis was determined by staining with oil-red O and reverse transcription polymerase chain reaction assessments of lipoprotein lipase, leptin, adiponectin and adipocyte genes at different time intervals, after 4, 7, 14, and 21 days. Our results revealed that the pattern of CD marker expression was highly positive significant with CD29, CD44, and CD90 when compared with CD34 and CD45. MSCs showed proliferative potential and were capable of adipogenic differentiation characterized by reddish brown-droplets following staining with oil-red O and expression of molecular bands of genes. These results demonstrate, at the morphological, immunophenotyping and gene expression levels, the multipotency of MSCs and thus highlight their potential therapeutic value for cell-based tissue engineering.
Adipocytes ; Adipogenesis* ; Adiponectin ; Animals ; Bone Marrow ; Flow Cytometry ; Follow-Up Studies* ; Gene Expression* ; Immunophenotyping* ; Leptin ; Lipoprotein Lipase ; Mesenchymal Stromal Cells* ; Polymerase Chain Reaction ; Rats* ; Reverse Transcription ; Tissue Engineering ; Transplants

Mesenchymal stem cells (MSCs) offer significant promise as a multipotent source for cell-based therapies and could form the basis for the differentiation and cultivation of tissue grafts to replace damaged tissue. However, no gene expression follow up analysis has been undertaken to characterize the in vitro adipogenic differentiated MSCs. The main goal of this study was to focus on MSCs and to analyze their differentiation capacity. To achieve this aim, bone marrow MSCs from sprague dawely rats were isolated, expanded in monolayer culture and characterized with respect to their cluster of differentiation (CD) and ability for adipogenic differentiation capacity. The expression of CD44, CD45, CD29, CD34, and CD90 on bone marrow derived MSCs was characterized using flow cytometry. Adipogenesis was determined by staining with oil-red O and reverse transcription polymerase chain reaction assessments of lipoprotein lipase, leptin, adiponectin and adipocyte genes at different time intervals, after 4, 7, 14, and 21 days. Our results revealed that the pattern of CD marker expression was highly positive significant with CD29, CD44, and CD90 when compared with CD34 and CD45. MSCs showed proliferative potential and were capable of adipogenic differentiation characterized by reddish brown-droplets following staining with oil-red O and expression of molecular bands of genes. These results demonstrate, at the morphological, immunophenotyping and gene expression levels, the multipotency of MSCs and thus highlight their potential therapeutic value for cell-based tissue engineering.
Adipocytes ; Adipogenesis* ; Adiponectin ; Animals ; Bone Marrow ; Flow Cytometry ; Follow-Up Studies* ; Gene Expression* ; Immunophenotyping* ; Leptin ; Lipoprotein Lipase ; Mesenchymal Stromal Cells* ; Polymerase Chain Reaction ; Rats* ; Reverse Transcription ; Tissue Engineering ; Transplants

BACKGROUND AND OBJECTIVES: Cisplatin is a nephrotoxic chemotherapeutic agent. So, preventive measures worth to be evaluated. Human amniotic fluid stem cells (hAFSCs) in prevention or amelioration of cisplatin-induced acute kidney injury (AKI) in Sprague-Dawley rates have been tested. METHODS: 80 Sprague-Dawley rats (250~300 g) were used and divided into 4 major groups, 20 rats each. Group I: Saline-injected group. Group II: Cisplatin-injected group (5 mg/kg I.P). Group III: Cisplatin-injected and hAFSCs-treated group (5×106 hAFSCs I.V. one day after cisplatin administration). Group IV: Cisplatin-injected and culture media-treated group. Each major group was further divided into 4 equal subgroups according to the timing of sacrifice; 4, 7, 11 and 30 days post-cisplatin injection. Renal function tests were done. Kidney tissue homogenate oxidative stress parameters malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) were determined. Histopathological scoring systems for active injury, regenerative and chronic changes were analyzed separately. RESULTS: hAFSCs characterization and differentiation was proved. Cisplatin injection resulted in a significant increase in serum creatinine and MDA and decrease in SOD, GSH and creatinine clearance. These changes were attenuated early by day 4 with the use of hAFSCs. Cisplatin injection induced tubular necrosis, atrophy, inflammatory cells infiltration and fibrosis. The use of hAFSCs was associated with significantly lowered injury score at day 4, 7, 11 and 30 with marked regenerative changes starting from day 4. CONCLUSION: hAFSCs have both a protective and regenerative activities largely through an antioxidant activity. This activity cut short the acuteness of cisplatin nephrotoxicity.
Acute Kidney Injury ; Amniotic Fluid ; Animals ; Atrophy ; Cisplatin ; Creatinine ; Female ; Fibrosis ; Glutathione ; Humans ; Kidney ; Malondialdehyde ; Mesenchymal Stromal Cells* ; Necrosis ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley* ; Stem Cells ; Superoxide Dismutase

BACKGROUND AND OBJECTIVES: Stem cell technology offers a new hope for many chronic disorders patients. The types of stem cells are different with many differences existing between each type. Mesenchymal stem cells (MSCs) represent one type of adult stem cells that can be easily isolated, then re-transplanted to the patients. This offers potential for their future application in treating many disorders without fear of rejection possibility. MSCs can be isolated from different sources e.g. bone marrow (BMSCs) and adipose tissue (ADSCs). In the present study we compared BMSCs and ADSCs isolated from Sprague-Dawley rats. METHODS AND RESULTS: For this comparison, immunophenotyping, the analysis of growth rates, proliferation by colony forming unit-fibroblast assay, population doubling time, and trilineage differentiation assays were performed for both BMSCs and ADSCs. The findings revealed that despite no difference in immunphenotypic character between BMSC and ADSC, a better proliferative capacity was observed for ADSCs which would advocate their better use in regenerative applications. On the other hand, BMSCs showed more potential for osteogenic and chondrogenic differentiation. CONCLUSIONS: Our study showed that, despite many similarities between both types of cells, there are differences existing which can offer assistance on choosing type of cell to be used in specific diseases. Although ADSCs seem more promising for regenerative application generally, BMSCs may represent a better choice for treating bone disorders.
Adipose Tissue* ; Adult Stem Cells ; Animals ; Bone Marrow* ; Hand ; Hope ; Humans ; Immunophenotyping ; Mesenchymal Stromal Cells* ; Rats* ; Rats, Sprague-Dawley ; Stem Cells

BACKGROUND: In severe chronic stages of emphysema the only treatment is lung transplantation. SO, an urgent need exists for the development of effective treatments. Stem cells therapy arises as a new therapeutic approach. AIM OF THE WORK: To investigate whether bone marrow mononuclar cells (BMMNCs) can promote lung regeneration and decrease apoptosis in lipopolysaccharide (LPS) induced pulmonary emphysema in C57Bl/6 mice. MATERIAL AND METHODS: 14 weeks old female mice (C57Bl/6), weighing around 25 g were used in this study. The mice were divided into 4 groups (10 in each group): group A: mice received no treatment, group B: mice received intranasal instillation of LPS with no further treatment, group C: mice received intranasal instillation of LPS then given a dose of BMMNCs and evaluated 21 days later and group D: the mice that received intranasal instillation of LPS then given a dose of Dulbecco's Modified Eagle's Medium (DMEM) and evaluated 21 days later. Imaging analysis was done using imagej program. To measure apoptotic index, Anti-caspase 3 polyclonal antibody staining was done. RESULTS: Analysis of the mean of airspace equivalent diameters (D0) and its statistical distribution (D1) for the different groups allowed to observe that group treated with BMMNCs (group C) showed the significant improvement in D0 and D1 than the group received LPS only (group B). Analysis of apoptotic index showed significant difference between BMMNCs treated group (group C) and that received LPS only (group B). CONCLUSIONS: BMMNCs effectively promote lung regeneration and reduction of apoptosis in pulmonary emphysema.
Animals ; Apoptosis* ; Bone Marrow* ; Emphysema ; Female ; Humans ; Lung Transplantation ; Lung* ; Mice ; Pulmonary Emphysema* ; Regeneration* ; Stem Cells

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.