Study of the Effect of Route of Administration of Mesenchymal Stem Cells on Cisplatin-Induced Acute Kidney Injury in Sprague Dawley Rats

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.

The Effect of Bone Marrow Mononuclear Cells on Lung Regeneration and Apoptosis in a Simple Model of Pulmonary Emphysema

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.

Adipogenesis of Sprague Dawely rats mesenchymal stem cells: a morphological, immunophenotyping and gene expression follow-up study / 대한해부학회지

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.

Adipogenesis of Sprague Dawely rats mesenchymal stem cells: a morphological, immunophenotyping and gene expression follow-up study / 대한해부학회지

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.

Serum leptin, insulin and parathyroid hormone levels in chronic renal failure patients

Chronic renal failure patients whether they are treated with hemodialysis or on conservative treatment frequently suffer uremic anorexia and malnutrition, which is associated with increased morbidity and mortality. In this study we have measured serum leptin, serum insulin and parathyroid hormone in addition to routine kidney function tests, serum glucose, total protein, albumin, lipogram, total serum calcium and inorganic phosphorus. This study was conducted on forty five male patients with chronic renal failure and ten healthy male subjects as control group [Group I.]. According to management of chronic renal failure the patients were divided into two groups: 22 patients on conservative treatment [Group II] and 23 patients on hemodialysis [Group III]. Serum levels of both leptin and insulin revealed significant elevation in patient groups [either on conservative or on hemodialysis,] compared to controls, also in hemodialysis group compared to group on conservative treatment. Serum level of intact parathyroid hormone, also showed significant elevation in groups II and III compared to controls with no difference in comparing group Ill versus group II. Correlation study in whole patients group revealed significant negative correlations between creatinine clearance with both leptin and insulin. Also significant positive correlations were found between leptin and insulin and between leptin and intact parathyroid hormone [iPTH]. Anorexia was found in both patient groups II and III [90.9% and 91.3% respectively,]. Chronic renal failure patients have hyperleptinemia and hyperinsulinemia and there are important interactions between leptin and insulin in which each hormone may be involved in regulating the function of the other. Excess parathyroid hormone may play a role in the pathogenesis of both hyperleptinemia and hyperinsulinemia. Hyperleptinemia may be an important contributing factor for uremic anorexia

Basiliximab reduces the incudence of acute cellular rejection in live related donor kidney transplatation; a single centre experience

The aim of this work is to determine the therapeutic benefit [s] of basiliximab induction therapy in the living related donor kidney transplantation One hundred adult recipients of their first kidney allograft were randomized to two treatment groups, one group received basiliximab and the second served as a control. All patients received a maintenance triple immunosuppressive therapy [steroids, cyclosporine, microemulsion and azathioprine]. The patients were followed up for a minimum of one year. The end points of evaluations included the incidence of acute rejection episodes, severity of rejection, cumulative steroid dose received, patients and graft survival. Basiliximab significantly reduced the proportion of patients who experienced of patients who experienced an acute rejection [18/50] when compared to the control group [31/50]. The cumulative steroid dose at 3 months as well as at 12 months was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable among the two treatment groups. Prophylactic basiliximab is well tolerated and significantly reduces the incidence of acute refection episodes in living related donor kidney transplantation

Growth in children with chronic renal faliure and after transplantation

This study aimed at studying the relation between height, glomerular filtration rate [GFR] and hormonal alteration in children with chronic renal failure [CRF] on regular hemodialysis [HD] and the possible role of normal graft function, after kidney transplantation, in this respect. The study population comprised 18 children with CRF on HD with mean age of 10.56 +/- 3.08 years and 16 children with normal graft function [mean age 11.06 +/- 3.19]. Mean duration on HD was 14.72 +/- 7.73 months for CRF group. Mean interval after transplantation was 1.97 +/- 0.9 years for the group of functioning grafts. Ten normal healthy children of matched age and sex served as controls. All patients were subjected to assessment of growth parameters including height, expressed as standard deviation scores [HtSDS] for chronological age, measurement of serum growth hormone [hGH] and serum parathormone [PTH] by radioimmunoassay. Growth performance was evaluated twice: at the start of the study and after a period of one year. The overall growth retardation in children with CRF on HD corresponded to -3.16 +/- 0.43 [mean SDS for height]. Children with normal graft function had a mean HtSDS of -2.54 +/- 0.29. Growth retardation remained a critical complication after kidney transplantation despite the statistically significant improvement observed compared to the group of children with CRF [P< 0.001]. Our results confirmed that impaired HtSDS with children with CRF correlates with the duration on hemodialysis [r = -0.728, P< 0.001]. There was a significant correlation between GFR and PTH level [r = -0.750, P< 0.001] in children with CRF. Our series of children with CRF had a positive correlation between their SDS for height and GFR [r =0.760 with P<0.001]. Both categories with CRF and with normal graft function had significantly higher levels of both serum hGH and PTH compared to controls [P<0.001], while CRF children had significantly higher serum levels of both hGH and PTH compared to those with normal graft function [P<0.008 and P<0.001 respectively]. Our results support the possibility that growth retardation in children with CRF despite the normal or elevated hGH level may be explained by the presence of peripheral insensitivity to the action of hGH

Value of otoacoustic emission in monitoring hearing acuity in chronic renal failure patients

Evaluation of hearing acuity using the conventional pure-tone audiometry was performed in 48 patients less than 40 years of age as well as 15 age and sex matched healthy subjects as controls [group I]. Twenty-two patients were treated conservatively [group II] and twenty-six patients on regular hemodialysis HD [group III] who were further classified according to the duration of HD into fourteen patients dialyzed for l year [group IIIb]. The transient evoked otoacoustic emission [TEOAE] method was applied only for patients proved to have normal pure tone thresholds. The percentages of patients with sensorineural hearing loss [SNHL] in groups [II]and [III] were 22.7% and 15.3%, respectively, utilizing the pure-tone audiometry method. The results revealed that hearing acuity was found to be impaired in chronic renal failure patients whether conservatively treated or hemodialyzed. The transient evoked otoacoustic emission is better than the conventional pure-tone audiometry for evaluation of hearing acuity in this setting

Echocaridographic evaluation of tricuspid valve diseases

In a trial to elucidate the role of echocardiography in evaluation of tricuspid valve [TV] diseases, sixty-four patients were studied in addition to 20 age-matched control. On clinico-echocardiographic basis, 6 groups of patients were identified. Functional tricuspid regurge [TR] secondary to rheumatic mitral and aortic lesions [51 patients], functional TR associated with atrial septal defect [ASD] [4] with cor pulmonale [4], with pulmonary stenosis [2], organic TR and tricuspid stenosis [TS] of rheumatic aetiology [1] and organic TR due to Ebstein's anomaly [2]. With M-mode study, the anterior and septal leaflets of TV were identified in 39 cases [60.9%] and Ebstein's anomaly was suggested in 2 cases [3.12%]. 2-D echocardiography revealed systolic incoaptation of TV leaflets in 55 cases [85.9%], thickened and limited movement of septal leaflet of TV [TS; in a single case [1.6%], downward displacement of TV, atrialization of RV and huge RA [Ebstein's anomaly] in 2 cases [3.1%] and RA thrombus in a single case [1.6%] using apical-4-chamber view. ASD in 4 cases [6.3%] using subcostal view. It was possible to identify the 3 leaflets in 55 cases [85.9%], the anterior leaflet was best seen in the long axis -view, the septal one in the short axis view and the posterior leaflet was seen only in the long axis view. Measurements of TV annulus, cusp separation, RA and RV dimensions were significantly higher in patients than in controls. Doppler study confirmed the presence of TR in all cases. The regurgitation jet was directed anteriorly in 43 cases [67.2%] denoting anterior leaflet affection and to the interatrial septum in 21 cases [32.8%] denoting septal leaflet affection, confirmed ASD in 4 cases [6.3%], and confirmed TS in a single case [1.6%] and PS in two cases [2.1%] through estimation of maximum pressure gradient across the valve. Moreover, the pulmonary artery systolic pressure was estimated in all cases and it was found to be higher than normal in 52 cases [81.3%] due to rheumatic valvular diseases and in 4 cases [6.3%] due to obstructive lung diseases. These results suggest that echocardiographic study gives clear information about various diseases affecting TV

Effect of schistosomiasis on the living kidney donors

Twenty schistosomal living kidney donors were compared with 20 non schistosomal donors during a mean follow up period of 42 months [range 12-62 months]. All participants with schistosomasis had been treated preoperatively with anti-schistosomal chemotherapy. None of the donors developed significant change in mean systolic or diastolic blood pressuro along the follow up period. One schistosomal and 2 non-schistosomal donors demonstrated trace proteinuria. Microscopic haematuria was discovered in a single non-schistosomal donor. Both groups of donors demonstrated a comparable reduction in renal function after uninephrectomy. The response of the remaining kidney to combined infusion of dopamine and an amino acids preparation was similar in both groups. One schistosomal and two non-schistosomal donors developed mild hydroureteronephrosis on excretory urography. Schistosomiasis did not significantly affect compensatory hypertrophy of the remaining kidney. It could be concluded that uncomplicated schistosomasis of living kidney donors does not adversely affect either the function or the morphology of the remaining kidney, at least during observation period of 1-5 years. Moreover, schistosomal infection does not appear to alter the adaptive change in the remaining kidney provided that the donor had functionally and morphologically intact kidneys and that schistosomasis was treated before kidney donation. However, longer term evaluation is recommended to expand the validity of these results