Teratogenic effects induced by chitosan oligosaccharide in Wistar female rat Rattus norvegicus.

The aim of this research is to investigate the teratogenic effects of chitosan oligosaccharide in Wistar female rats (Rattus norvegicus). Chitosan LD50 value was calculated by probit analysis. High dose, 1/10 LD50 which equal to 150 mg/kg body weight, and low dose, 1/30 LD50 which equal to 50 mg/kg body weight, were administrated orally to Wistar female rats to examine the teratogenic effect during organogenesis period from 6th day to 15th day of gestation. Treated and control rats were sacrificed and their foetuses were examined for external, skeletal and visceral anomalies, number and length of foetuses and their weights. Obtained results showed toxicity and teratogenic effects of chitosan on treated rats and their progenies, i.e. high fetal mortality, offspring's weight and length reduction, and high incidence of fetal external, skeletal and visceral abnormalities. This suggested that chitosan is a teratogenic compound, restricted to current results from orally treated Wistar rats.

Stem cell therapy as a novel therapeutic intervention for resistant cases of alopecia areata and androgenetic alopecia.

BACKGROUND: Management of alopecia areata (AA) and androgenetic alopecia (AGA) is often challenging as patients may be resistant to currently available modalities of treatment. The use of stem cells may be a novel option for resistant cases. OBJECTIVE: To evaluate the safety and efficacy of the use of autologous bone marrow derived mononuclear cells (including stem cells) as compared to follicular stems cells for the management of resistant cases of AA and AGA. METHODS: This study included 40 patients (20 AA patients and 20 AGA patients), all patients were treated with a single session of intradermal injection of autologous stem cells (SCs) therapy. They were divided into four groups according to the applied modality [either autologous bone marrow derived mononuclear cells (bone marrow mononuclear cells [BMMCs] or autologous follicular stem cells [FSC]). RESULTS: Six months after stem cell therapy (SCT) injection, there was a significant improvement, confirmed by immunostaining and digital dermoscopy. The mean improvement in all groups was "very good". There was no significant difference between both methods in either type of alopecia. No serious adverse events were reported. CONCLUSION: Autologous BMMCs and FSC seem to be a safe tolerable and effective treatment for the management of both resistant AA and AGA.

Therapeutic Effect of Adipose Derived Stem Cells versus Atorvastatin on Amiodarone Induced Lung Injury in Male Rat.

BACKGROUND AND OBJECTIVES: Amiodarone (AM), a class 3 antiarrhythmic drug, has been associated with variety of adverse effects, the most serious of which is pulmonary toxicity. Ator (A) is a statin, known for their immunomodulatory and anti-inflammatory activities. Recent studies provide evidence of potential therapeutic effect of statins on lung injury. Adipose derived stem cells (ADSCs) have shown great promise in the repair of various tissues. The present study aimed at investigating and comparing the possible therapeutic effect of A and ADSCs on AM induced lung injury in albino rats. METHODS AND RESULTS: 34 adult male albino rats were divided into 5 groups: control group (Gp I), A group (Gp II) received 10 mg/kg of A orally 6 days (d)/week (w) for 4 weeks (ws), AM group (Gp III) received 30 mg/kg of AM orally 6 d/w for 4 ws, AM&A group (Gp IV) received AM for 4ws then A for other 4 ws and AM&SCs group (Gp V) received AM for 4 ws then injected with 0.5 ml ADSCs on 2 successive days intravenously (IV). Histological, histochemical, immunohistochemical and morphometric studies were performed. Group III displayed bronchiolitis obliterans, thickened interalveolar septa (IAS) and thickened vascular wall which were proven morphometrically. Increased area% of collagen fibers and apoptotic changes were recorded. All findings regressed on A administration and ADSCs therapy. CONCLUSION: Ator proved a definite ameliorating effect on the degenerative, inflammatory, apoptotic and fibrotic changes induced by AM. ADSCs administration denoted more remarkable therapeutic effect compared to A.

Comparative Histological Study on the Therapeutic Effect of Green Tea and Stem Cells in Alzheimer's Disease Complicating Experimentally Induced Diabetes.

BACKGROUND AND OBJECTIVES: Alzheimer's disease (AD) is a devastating neurodegenerative disorder. Increasing evidence implicates diabetes mellitus (DM) as a risk factor for AD. Green tea (GT) has several beneficial effects attributed to its anti-oxidant phenolic compounds. Adipose tissue is a rich source of adipose-derived mesenchymal stem cells (ADSCs). This study was designed to evaluate and compare the possible therapeutic effect of green tea extract (GTE) and ADSCs on AD complicating induced DM in male rat. METHODS: 31 adult male albino rats were divided into 5 groups. Group I (Control), Group II received GTE, 50 mg/kg daily orally for 4 weeks, Group III received a single intraperitoneal injection of Streptozotocin (STZ), 50 mg/kg, Group IV: received STZ followed by GTE and Group V: received STZ followed by human ADSCs (hADSCs) intravenously. RESULTS: Multiple acidophilic masses, deformed neurons, Congo red +ve masses and Caspase 3 +ve neurons were seen in group III, became few in group IV and occasional in group V. Multiple Prussian blue +ve cells were detected in group V. Some CD44 +ve cells were noticed in group III, became multiple in groups IV and V. The mean area of neurons exhibiting acidophilic cytoplasm, mean area of amyloid plaques and mean area % of Caspase 3 +ve cells indicated a significant increase in group III. The mean area % of CD44 +ve cells recorded a significant increase in group IV. CONCLUSIONS: hADSCs exerted a more marked therapeutic effect on the neurodegenerative changes complicating DM and corresponding to AD.

Plasma D-dimer as a Prognostic Marker in ICU Admitted Egyptian Children with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in children. This study aimed at evaluation of the D-dimer blood levels as a new marker to predict prognosis and outcome of traumatic brain injuries among children. MATERIALS AND METHODS: This case control study was conducted at the Paediatric Intensive Care Unit (ICU), Alharm Hospital in Giza, Egypt during 2012-2013, on 46 Paediatric cases admitted to ICU with head injury and 20 normal age-matched controls. Clinical data and venous blood samples were prospectively collected at 1(st), 3(rd) and 14(th) day of admission, in addition to examination finding as Glasgow coma scale (GCS), cranial brain computed tomography (CT), routine laboratory investigations (CBC, CRP, SGOT, SGPT, urea, creatinine, random blood glucose, Na, K and arterial blood gases) plasma D-dimer, INR, PT, aPTT and PC. Data analysis was carried out accordingly and ROC curve was performed to explore the discriminating ability of D-dimer through estimation of its accuracy in differentiating temporal survivorship of those with TBI. RESULTS: Cases were classified according to outcome into survivors and non-survivors. Significant difference was observed between cases and controls and between survivors and non-survivors during 1(st), 3(rd) and 14(th) day of the follow up including GCS, blood levels of D-dimer, PT and aPTT. ROC curve analysis for D-dimer showed decline in both sensitivity from 89.5% to 73.7% and specificity from 100% to 81.5% along the study days respectively. D-dimer time measurements showed significant decline among survivors from 4.2 to 0.7, while in the non survivor group this decline was much higher from 27.9 to 1.4. CONCLUSION: Low plasma D-dimer suggests the absence of brain injury, and good prognosis.

Comparative Study between Intravenous and Intraperitoneal Stem Cell Therapy in Amiodarone Induced Lung Injury in Rat.

BACKGROUND AND OBJECTIVES: The fibrosing form of lung injury (occupational, environmental, infective or drug induced) is associated with significant morbidity and mortality. Amiodarone (AM), often prescribed for control of arrhythmias is considered a potential cause. No effective treatment was confirmed, except lung transplantation. Intravenous (IV) stem cell therapy may produce pulmonary emboli or infarctions. Despite being commonly used in clinical practice, the intraperitoneal (IP.) route has been rarely used for cell delivery. The present study aimed at investigating and comparing the possible effect of IP stem cell therapy (SCT) on pulmonary toxicity versus the intravenous route in a rat model of amiodarone induced lung damage. METHODS AND RESULTS: 36 adult male albino rats were divided into 4 groups. Rats of AM group were given 30 mg/kg daily orally for 4 weeks. Rats of IV SCT group were injected with stem cells in the tail vein. Rats of IP SCT group received IP cell therapy. Histological, histochemical, immunohistochemical and morphometric studies were performed. Obstructed bronchioles, overdistended alveoli, reduced type I pneumocytes, increased thickness of alveolar septa and vessels wall besides increased area% of collagen fibers regressed in response to IV and IP SCT. The improvement was more obvious in IV group. The area% of Prussion blue +ve and CD105 +ve cells was significantly higher in IV group. CONCLUSIONS: Cord blood MSC therapy proved definite amelioration of lung injury ending in fibrosis. The effect of IP SCT was slightly inferior to that of IV SCT, which may be overwhelmed by repeated IP injection.

Histological experimental study on the effect of stem cell therapy on adriamycin induced chemobrain.

BACKGROUND AND OBJECTIVES: Negative consequences of chemotherapy on brain function were suggested and were addressed in animal models as the clinical phenomenon of chemobrain .It was postulated that adriamycin (ADR) induce changes in behaviour and in brain morphology. Human umbilical cord mesenchymal stem cells (HUCMSCs) could be induced to differentiate into neuron-like cells .The present study aimed at investigating the possible therapeutic effect of HUCMSC therapy on adriamycin induced chemobrain in rat. METHODS AND RESULTS: Twenty five female albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg ADR. The rats were sacrificed two and four weeks following confirmation of brain damage. In stem cell therapy group, rats were injected with HUCMSCs following confirmation of brain damage and sacrificed two and four weeks after therapy. Brain sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In ADR group, multiple shrunken neurons exhibiting dark nuclei and surrounded by vacuoles were seen .In response to SC therapy ,multiple normal pyramidal nerve cells were noted. The area of shrunken nerve cells exhibiting dark nuclei, Prussion blue and CD105 positive cells were significantly different in ADR group in comparison to SC therapy group. CONCLUSIONS: ADR induced progressive duration dependant cerebral degenerative changes. These changes were ameliorated following cord blood human mesenchymal stem cell therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.

Experimental study on the effect of intravenous stem cell therapy on intestinal ischemia reperfusion induced myocardial injury.

BACKGROUND AND OBJECTIVES: The myocyte death that follows intestinal ischemia reperfusion (I/R) injury is a major factor contributing to high mortality and morbidity in ischemic heart disease. The purpose of stem cell (SC) therapy for myocardial infarction is to improve clinical outcomes. The present study aimed at investigating the possible therapeutic effect of intravenous human cord blood mesenchymal stem cells (HCBMSCs) on intestinal ischemia reperfusion induced cardiac muscle injury in albino rat. METHODS AND RESULTS: Thirty male albino rats were divided equally into control (Sham-operated) group, I/R group where rats were exposed to superior mesenteric artery ligation for 1 hour followed by 1 hour reperfusion. In SC therapy group, the rats were injected with HCBMSCs into the tail vein. The rats were sacrificed four weeks following therapy. Cardiac muscle sections were exposed to histological, histochemical, immunohistochemical and morphometric studies. In I/R group, multiple fibers exhibited deeply acidophilic sarcoplasm with lost striations and multiple fibroblasts appeared among the muscle fibers. In SC therapy group, few fibers appeared with deeply acidophilic sarcoplasm and lost striations. Mean area of muscle fibers with deeply acidophilic sarcoplasm and mean area% of fibroblasts were significantly decreased compared to I/R group. Prussion blue and CD105 positive cells were found in SC therapy group among the muscle fibers, inside and near blood vessels. CONCLUSIONS: Intestinal I/R induced cardiac muscle degenerative changes. These changes were ameliorated following HCBMSC therapy. A reciprocal relation was recorded between the extent of regeneration and the existence of undifferentiated mesenchymal stem cells.

Effect of stem cell therapy on induced diabetic keratopathy in albino rat.

BACKGROUND AND OBJECTIVES: Type 2 diabetes mellitus (DM) is a prevalent disorder. Diabetic keratopathy is a well-known ocular complication secondary to type 2 DM. Topical insulin application did not affect apoptosis and necrosis levels in corneal epithelium. Autologous cell transplantation is not a viable option for diabetic patients with bilateral limbal stem cell deficiency. The present study aimed at assessing the possible effect of hemopoeitic stem cell (HSC) therapy on induced diabetic keratopathy in albino rat. METHODS AND RESULTS: Fifteen male albino rats were divided into control group of 2 rats, diabetic group of 8 rats receiving single intraperitoneal (IP) injection of 50 mg/kg streptozotocin (STZ). 3 animals were sacrificed 6 weeks following confirmation of diabetes to confirm keratopathy and 5 rats were sacrificed 4 weeks following confirmation of keratopathy. SC therapy group included 5 rats injected with HSCs 6 weeks following confirmation of diabetes and sacrificed 4 weeks following SC therapy. Cord blood collection, stem cells isolation and labeling were performed. Eye specimens were subjected to histological, histochemical, immunohistochemical, morphometric and statistical studies. In diabetic group, the central cornea showed multiple cells with vacuolated cytoplasm and dark nuclei, focal epithelial discontinuity, reduced corneal thickness and less number of layers of corneal and conjunctival epithelia. In stem cell therapy group, few cells with vacuolated cytoplasm and dark nuclei were found in the corneal and conjunctival epithelia with more number of epithelial layers. CONCLUSIONS: A definite ameliorating effect of HSC therapy was detected on diabetic keratopathy. The therapeutic cells were effective in limiting corneal epithelial changes.

Tissue regeneration and stem cell distribution in adriamycin induced glomerulopathy.

BACKGROUND AND OBJECTIVES: Glomerulosclerosis develops secondary to various kidney diseases. It was postulated that adriamycin (ADR) induce chronic glomerulopathy. Treatment combinations for one year did not significantly modify renal function in resistant focal segmental glomerulosclerosis (FSGS). Recurrence of FSGS after renal transplantation impacts long-term graft survival and limits access to transplantation. The present study aimed at investigating the relation between the possible therapeutic effect of human mesenchymal stem cells (HMSCs), isolated from cord blood on glomerular damage and their distribution by using ADR induced nephrotoxicity as a model in albino rat. METHODS AND RESULTS: Thirty three male albino rats were divided into control group, ADR group where rats were given single intraperitoneal (IP) injection of 5 mg/kg adriamycin. The rats were sacrificed 10, 20 and 30 days following confirmation of glomerular injury. In stem cell therapy group, rats were injected with HMSCs following confirmation of renal injury and sacrificed 10, 20 and 30 days after HMSCs therapy. Kidney sections were exposed to histological, histochemical, immunohistochemical, morphometric and serological studies. In response to SC therapy multiple Malpighian corpuscles (MC) appeared with patent Bowman's space (Bs) 10 and 20 days following therapy. One month following therapy no remarkable shrunken glomeruli were evident. Glomerular area and serum creatinine were significantly different in ADR group in comparison to control and SC therapy groups. CONCLUSIONS: ADR induced glomerulosclerosis regressed in response to cord blood HMSC therapy. A reciprocal relation was recorded between the extent of renal regeneration and the distribution of undifferentiated mesenchymal stem cells.

Effect of stem cell therapy on amiodarone induced fibrosing interstitial lung disease in albino rat.

BACKGROUND AND OBJECTIVES: The fibrosing forms of interstitial lung disease (ILD) are associated with significant morbidity and mortality. ILD may be idiopathic, secondary to occupational, infection, complicate rheumatic diseases or drug induced. Efficacy of antifibrotic agents is as far as, limited and uncertain. No effective treatment was confirmed for pulmonary fibrosis except lung transplantation. The present study aimed at investigating the possible effect of human cord blood mesenchymal stem cell (MSC) therapy on fibrosing ILD. This was accomplished by using amiodarone as a model of induced lung damage in albino rat. METHODS AND RESULTS: Seventeen adult male albino rats were divided into 3 groups. Rats of amiodarone group were given 30 mg/kg of amiodarone orally 6 days/ week for 6 weeks. Rats of stem cell therapy group were injected with stem cells in the tail vein following confirmation of lung damage and left for 4 weeks before sacrifice. Obstructed bronchioles, thickened interalveolar septa and thickened wall of pulmonary vessels were found and proved morphometrically. Reduced type I pneumocytes and increased area% of collagen fibers were recorded. All findings regressed on stem cell therapy. CONCLUSIONS: Cord blood MSC therapy proved definite amelioration of fibrosing interstitial lung disease provided therapy starts early in the development of the pathogenesis.