Effects Of Stem Cell Treatment Research Articles

Cellular therapy for the peripheral arterial disease treatment: Protocol for a systematic review and meta-analysis.

Cellular therapy is a promising treatment option for Peripheral Arterial Disease (PAD). Different cell types can be used to regenerate and repair tissues affected by PAD. Many studies have proposed the use of stem cells, such as mesenchymal stem cells, or even mononuclear cells isolated from peripheral blood or bone marrow, to treat PAD. This paper reports a protocol of systematic review and meta-analysis that aims to identify the effects of stem cell treatment in patients with peripheral arterial disease. The search will be conducted in the following database: PubMed/MEDLINE, Clinicaltrial.gov, Scopus, Embase, Epistemonikos, Web of Science and Cochrane Library. Studies will be selected independently by two reviewers and will include all published randomized and non-randomized clinical trials. The data extraction will include studies population characteristics, type of treatment and main outcomes. We will assess the methodological quality of the studies using the Cochrane Risk of Bias 2.0 and Risk of Bias in Non-randomized Studies of Interventions. The certainty of the evidence will be rate using the Grading of Recommendations, Assessment, Development, and Evaluations. The findings will be presented in narrative summary tables and in a meta-analysis.

Stem Cells Rehabilitate Diabetic Neuropathy

To report the effectiveness of stem cell treatment in diabetic neuropathy. This study recruited 83 Iraqi females from 45 to 73 years old who had NIDDM between August 31, 2020 and June 30, 2023. All of them had a "Diabetic neuropathy symptom score (DNS)" (grade 3–4) and a "Diabetic foot sensory neuropathy score" (grade 1-2). They all had HbA1c (10-13%) from 7 to 10 years. The patient/family provided informed permission when they visited the "Al Zahrawy Center for Stem Cells in Baghdad". For four treatment sessions (once every three weeks), Hamad dispersed stem cells around the tibial and deep peroneal nerves. Among 83 Iraqi females, 49 (59.1%) had a grade 4 "Diabetic neuropathy symptom score" upon presentation, which decreased to 24.2% in 20 females after three months of medication. Their "Diabetic foot sensory neuropathy (DNS)" was (54.3%) in 45 females at presentation and decreased to (21.8%) in 18 females after three months of treatment. The satisfaction rate for therapy was 74.6% for the "Diabetic neuropathy symptom score" and 78.3% for "Diabetic foot sensory neuropathy (DNS)". Stem cell therapy is a good treatment option for diabetic neuropathy. The researchers supported it and suggested a greater sample size in other places.

Stem Cell Treatment for Dilated Cardiomyopathy: A Review of Recent Scientific Advances

Cardiomyopathy, a disorder of mechanical and electrical cardiac action, is a significant cause of morbidity and mortality in the United States and is seen in both adult and pediatric populations. Dilated cardiomyopathy, a subtype involving pathological enlargement of the heart, in particular causes significant reduction in quality of life and is a significant risk factor for heart failure development. Traditional treatment for dilated cardiomyopathy largely focuses on symptomatic relief and delayed progression of disease but does not offer a cure or reversal of disease process. In the past few decades, stem cell therapy has become a promising therapeutic because these cells can differentiate into human cardiomyocytes and offer a potential restoration of normal cardiomyocyte function. This review highlights 3 methodological derivations of cardiomyocytes: bone marrow–derived hematopoietic stem cells, mesenchymal stem cells, and adipose-derived stem cells. While most of the current research has focused on hematopoietic stem cells for dilated cardiomyopathy, further research is needed to elucidate which stem cell line is superior and most effective for disease treatment and reversal. This review highlights future directions of this line of research, such as direct comparison between cell types, analysis of the long-term effects of stem cell treatment, increased sample sizes, and potential use of this treatment in the pediatric and adult populations.

Epidermolysis Bullosa: Innovative Treatment with Stem Cells, a Systematic Review

Introduction: epidermolysis bullosa is a set of genetic disorders that originate from modifications in certain skin proteins that alter the union and structure of the dermis and epidermis. Clinically, it manifests itself through blisters. However, these lesions can spread to other areas. areas of the body, thus causing the appearance of chronic wounds. The conventional treatment of Epidermolysis Bullosa has not been shown to improve the long-term quality of life of those who suffer from it, which is why researchers propose new therapies that allow improvements in the quality of life of patients, being one of the most promising, the use of stem cells. Methods: randomized clinical trials were selected that evaluated the efficacy and safety of stem cell treatment in patients with Epidermolysis bullosa compared to usual therapy and its cost-effectiveness. Results: based on the selected articles, several variables were measured. Four articles demonstrated the effectiveness of stem cell treatment compared to conventional treatment; two articles measured the economic considerations and access to this new treatment; four articles compared the benefits and disadvantages of using stem cells in patients with Epidermolysis bullosa; and finally, five articles demonstrated the impact that stem cells have in improving the quality of life of patients with Epidermolysis bullosa who undergo this type of therapy. Conclusions: at a global level, the effectiveness of the use of stem cells opens a promising research perspective that seeks to benefit the most vulnerable population affected by this disease, since it plays a key role in the significant reduction of blistering lesions, this represents a positive advance. in the management of the disease, as well as the improvement in its biological, psychological and social sphere, allowing an early introduction to daily activities, generating significant savings of resources for caregivers and for the State. Because, in Latin America, to date there is little research in this area, it should be considered a very promising line of research in the field of Dermatology. Similar situation in the case of Ecuador, where since there are no statistics on patients with this disease, nor data that contribute to the treatment of this vulnerable group, these investigations will provide a solid basis for researchers to adopt this new therapy

Magnetic resonance imaging assessment of the therapeutic effect of combined electroacupuncture and stem cells in acute peripheral nerve injury.

Objectives: This study aimed to evaluate the therapeutic effect of a combination of Bone Mesenchymal stem cells (BMSCs) transplantation and Electroacupuncture (EA) for acute sciatic nerve injury in rats using magnetic resonance. Methods: Ninety-two male adult healthy Sprague-Dawley rats were randomly divided into the EA+BMSCs group, EA group, MSCs group, and PBS group (control). Electroacupuncture was performed on a rat receiving EA treatment at Huantiao (GB30) and Zusanli (ST36). T2 values and diffusion tensor imaging (DTI) derived from multiparametric magnetic resonance imaging (MRI), histological assessments, and immunohistochemistry was used to monitor nerve regeneration. Walking track analysis was used to assess nerve functional recovery. Repeated-measures one-way analysis of variance was used to evaluate the significance of T2, DTI, and SFI values among the four groups. One-way analysis of variance was used for comparing the histological characteristics. Bonferroni test was used for multiple pairwise comparisons at each time point. Results: In terms of FA, the EA+BMSCs and EA groups had faster recovery than PBS (control) in all time points after surgery, and the EA+BMSCs group recovered better than the BMSCs group at 3 weeks (P ≤ 0.008). FA values were higher in the EA group than in the BMSCs group at 4 weeks (P ≤ 0.008). In terms of RD, the EA+BMSCs group recovered better than the BMSCs group at 2 and 4 weeks (P ≤ 0.008). Immunofluorescence staining for axon guidance molecule netrin-1 revealed that it was significantly higher in the EA+BMSCs subgroup and EA subgroup than it was in the control (PBS) subgroup at 1-3 weeks (P < 0.001). Immunofluorescence staining for S100 showed the continuity of nerve fibers recovered more quickly in the EA+BMSCs subgroup than in the BMSCs subgroup. Conclusion: Our research revealed that a combination of MSCs and EA can provide both topological and biomolecular guidance to promote axonal extension, myelin regeneration, and functional recovery after PNI. EA not only promotes nerve repair on its own, but also enhanced the beneficial effects of stem cell treatment and the secretion of netrin 1, a guidance regeneration factor, and promotes the orderly growth of nerve fibers. These PNI repairs could be monitored non-invasively and in situ by MRI. The FA and RD values derived from MRI could be sensitive biomarkers to reflect the PNI repair process.

Prospect of Stem Cells as Promising Therapy for Brachial Plexus Injury: A Systematic Review.

BackgroundBrachial plexus injury is an advanced and devastating neurological injury, for which both nerve surgery and tendon transfers sometimes remain insufficient in restoring normal movement. Stem cell therapy may be applicable to rescue the injured motor neurons from degeneration which potentially improves muscle strength.Study DesignSystematic Review; Level of evidence V.Data SourcesA systematic literature search was conducted on PubMed (MEDLINE), EMBASE, the Cochrane Library, and Scopus using the terms (“stem cell”) AND (“brachial plexus”) as search keywords.MethodsThe process of study selection was summarized by PRISMA flow diagram. The study included in vivo and in vitro studies with English language, humans or animals with some brachial plexus injuries, interventions, some applications of stem cells to the groups of study, with functional, biomechanical, or safety outcomes.ResultsIn total, there were 199 studies identified from the literature sources where 75 articles were qualified for forward evaluation following selecting the titles and abstracts. Ten studies were finally included in this systematic review after full-text assessment. Stem cells can produce neurotrophic factors in vitro and in vivo in rats, and their level was increased after injury. Electrophysiological measurement showed that the intervention group had distinctly higher CMAP amplitude and evidently shorter CMAP latency than the model group. Application of bone marrow stem cells (BMSCs) showed an elevation in the numbers of axons and density of myelinated fibers, the density of nerve fibers, the diameter of regenerating axons, and a decrease in axonal degeneration. A study in humans indicated an improvement of the movements in a patient with traumatic total BPI after injection of Ad-MSC. It is associated with increased muscle mass and sensory recovery and also suggested that mononuclear cell injection enhances muscle regeneration and reinnervation in the partly denervated muscle of brachial plexus injury. Various muscle groups had obtained strength together with restoration, the muscle strength attained after the previous transplantation were preserved. The results of this review support stem cell treatment in brachial plexus injury.ConclusionThis review provides evidence of the positive effects of stem cell treatment in brachial plexus injury.

Effects of interaction between stem cells and degenerative retinal microenvironment on stem cell fate determination

<p indent=0mm>To date, a substantial amount of experimental data supports the safety and effectiveness of stem cell-based cell therapy in treating retinal degenerative diseases, thus, serving as a foundation for clinical studies. However, its therapeutic effect often declines or even disappears at a later stage. In addition to the characteristics of stem cells, the microenvironment in which stem cells are transplanted is likely a key factor that determines the fate of stem cells. Glial scar, chronic inflammation, and abnormal metabolic microenvironment in the retina often lead to the failure of long-term survival, correct differentiation, and integration of grafted stem cells in the retina, which may be important factors contributing to the failure of long-term therapeutic effect of stem cell treatment for retinal degenerative diseases. Alternatively, grafted stem cells may also actively regulate the degenerating retina through paracrine or material exchange with the host cells, which can help the fate determinant of grafted stem cells in the retina. Thus, the therapeutic effect of stem cell transplantation can be improved by combined-transplantation of different stem cells or by regulating the degenerative retinal microenvironment. This review summarizes the recent progress in interactions between grafted stem cells and degenerative host retina and their impact on stem cell fate determination.

Effect of stem cell treatment on burn wounds: A systemic review and a meta-analysis.

A meta-analysis was performed to evaluate the effect of stem cells treatment in managing burn wounds. A systematic literature search up to March 2022 incorporated 24 studies reported between 2013 and 2021 including 400 animals with burn wounds at the beginning of the study; 211 were using stem cells treatment, and 189 controlled. Statistical tools like the contentious method were used within a random or fixed-influence model to establish the mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of stem cells treatment in managing burn wounds. Stem cells treatment had a significantly higher burn wound healing rate (MD, 15.18; 95% CI, 11.29-19.07, P< .001), higher blood vessel number (MD, 12.28; 95% CI, 10.06-14.51, P< .001), higher vascular endothelial growth factor (MD, 10.24; 95% CI, 7.19-13.29, P< .001), lower interleukin-1 level (MD, -98.48; 95% CI, -155.33 to -41.63, P< .001), and lower tumour necrosis factor α level (MD, -28.71; 95% CI, -46.65 to -10.76, P< .002) compared with control in animals' models with burn wounds. Stem cells treatment had a significantly higher burn wound healing rate, higher blood vessel number, higher vascular endothelial growth factor, lower interleukin-1 level, and lower tumour necrosis factor α level compared with control in animals' models with burn wounds. Further studies are required to validate these findings.

Stem Cell Therapy for Pediatric Traumatic Brain Injury.

There has been a growing interest in the potential of stem cell transplantation as therapy for pediatric brain injuries. Studies in pre-clinical models of pediatric brain injury such as Traumatic Brain Injury (TBI) and neonatal hypoxia-ischemia (HI) have contributed to our understanding of the roles of endogenous stem cells in repair processes and functional recovery following brain injury, and the effects of exogenous stem cell transplantation on recovery from brain injury. Although only a handful of studies have evaluated these effects in models of pediatric TBI, many studies have evaluated stem cell transplantation therapy in models of neonatal HI which has a considerable overlap of injury pathology with pediatric TBI. In this review, we have summarized data on the effects of stem cell treatments on histopathological and functional outcomes in models of pediatric brain injury. Importantly, we have outlined evidence supporting the potential for stem cell transplantation to mitigate pathology of pediatric TBI including neuroinflammation and white matter injury, and challenges that will need to be addressed to incorporate these therapies to improve functional outcomes following pediatric TBI.

A bias-corrected meta-analysis model for combining, studies of different types and quality.

Public health researchers may have to decide whether to perform a meta-analysis including only high-quality randomized clinical trials (RCTs) or whether to include a mixture of all the available evidence, namely RCTs of varying quality and observational studies (OS). The main hurdle when combining disparate evidence in a meta-analysis is that we are not only combining results of interest but we are also combining multiple biases. Therefore, commonly applied meta-analysis methods may lead to misleadingconclusions. In this paper, we present a new Bayesian hierarchical model, called the bias-corrected (BC) meta-analysis model, to combine different study types in meta-analysis. This model is based on a mixture of two random effects distributions, where the first component corresponds to the model of interest and the second component to the hidden bias structure. In this way, the resulting model of interest is adjusted by the internal validity bias of the studies included in a systematicreview. We illustrate the BC model with two meta-analyses: The first one combines RCTs and OS to assess effectiveness of vaccination to prevent invasive pneumococcal disease. The second one investigates the effectiveness of stem cell treatment in heart disease patients. Our results show that ignoring internal validity bias in a meta-analysis may lead to misleading conclusions. However, if a meta-analysis model contemplates a bias adjustment, then RCTs results may increase their precision by including OS in the analysis. The BC model has been implemented in JAGS and R, which facilitate its application inpractice.

Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold.

Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. Acute liver failure was induced in mice using thioacetamide (TAA) (200mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. TAA dose was titrated until one-third mortality rate was achieved. TAA (200mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

STEM CELLS IN VETERINARY MEDICINE – FROM BIOLOGY TO CLINIC

Mesenchymal stem cells are adult stem cells found in different adult tissues such as adipose tissue, bone marrow, and also in umbilical blood. Mesenchymal stem cells are capable of differentiation into bone, cartilage and adipose tissue, and several reports also suggest that mesenchymal stem cells might be capable of transdifferentiation into muscle and neural cells. In addition to differentiation potential, mesenchymal stem cells might have other beneficial properties for pathological processes and studies in recent years suggest that mesenchymal stem cells have immunomodulatory, antiinflamatory and trophic actions, contributing to the healing processes in injured/diseased tissues. Osteorthritis is a chronic, progressive disorder with debilitating effects in both animals and humans. It is particularly common in some dog breeds, but also fairly common in humans. Currently, there is no cure for such conditions, but studies in recent years in both human and veterinary medicine suggest that mesenchymal stem cells might have beneficial effect on chronic osteoarthritis. In our laboratory, we have developed a novel method of treating osteoarthritis using autologous adipose tissue derived mesenchymal stem cells in dogs and horses. Stem cells are collected from patients’ adipose tissue, prepared in the laboratory and injected directly into affected joint(s). To prove the efficacy if this method, we have performed blind placebo study in dogs with bilateral osteoarthritis in knees, by treating one knee with stem cells and other knee with placebo (buffer used for cell delivery). Results of clinical examination revealed beneficial effect of stem cell treatment in osteoarthritic knees and x-ray imaging, and although with some limitations, results do suggest that degenerative processes in the knees treated with stem cells were limited or even reversed by the application of stem cells. Stem cells hold a great promise for the future of regenerative medicine, both veterinary and human, however, many questions about their use, potential and efficacy remain open and these will have to be studied and answered in the future years. Key words: dog; horse; stem cells; veterinary medicine

Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation in Patients With Cirrhosis

Peripheral blood stem cells (PBSCs) mobilized with colony-stimulating factor can promote liver regeneration and increase liver function in patients with liver diseases. However, thelong-term effects of stem cell treatments on survival and risk of hepatocellular carcinoma (HCC) in patients with cirrhosis have not been determined. We investigated the long-term effects of autologous stem cell transplantation and risk of HCC in patients with cirrhosis. We performed a retrospective analysis of 2 cohorts of patients with decompensated cirrhosis who received transplantations of autologous PBSCs (n= 282) or standard medical treatment (SMT, n= 286) in China from January 1, 2006, through December 31, 2016. Patients were followed up until death or liver transplantation. Mortality data were obtained by case records and confirmed by telephone calls. Survival time was calculated and HCC was confirmed by computed tomography or ultrasound. We used propensity score matching to adjust the differences between the 2 groups. Survival and incidence of HCC were analyzed and Cox proportional hazard regression was used to determine the prognostic factors. After propensity score matching, time of survival was significantly higher in the PBSC group than the SMT group (P= .001). The adjusted rate of 5-year survival was 71.2% in the PBSC group and 52.1% in the SMT group. The overall incidence of HCC did not differ significantly between the PBSC and SMT groups (21.1% vs 20.4%; P= .999). Significant improvement of liver functions was observed at 1 year, 2 years, 3 years, and 5 years after PBSC transplantation compared with the SMT group. In a long-term analysis of patients with decompensated cirrhosis, autologous transplants of PBSCs significantly improved long-term survival compared with a control group. PBSC transplant did not appear to increase the risk of HCC.

The combination of mannitol and temozolomide increases the effectiveness of stem cell treatment in a chronic stroke model

BackgroundThe blood-brain barrier (BBB) presents a significant challenge to the therapeutic efficacy of stem cells in chronic stroke. Various methods have been developed to increase BBB permeability, but these are associated with adverse effects and are, therefore, not clinically applicable. We recently identified that combination drug treatment of mannitol and temozolomide improved BBB permeability in vitro. Here, we investigated whether this combination could increase the effectiveness of stem cell treatment in an animal model of chronic ischemic stroke. MethodsChronic stroke was induced in rats by middle cerebral artery occlusion (MCAo). After then, rats were administered human umbilical cord–derived mesenchymal stromal cells (hUC-MSCs) by intravenous injection with or without combination drug treatment of mannitol and temozolomide. To evaluate the therapeutic efficacy, behavioral and immunohistochemical tests were performed, and the differences among control, stem cell only, combination drug only and stem cell with combination drug treatment were analyzed. ResultsAlthough no hUC-MSCs were detected in any group, treatment with stem cells and combination drug of mannitol and temozolomide increased the intracerebral delivery of hCD63-positive microvesicles compared with stem cell only treatment. Furthermore, treatment with stem cells and drug combination ameliorated behavioral deficits and increased bromodeoxyuridine-, doublecortin- and Reca-1–positive cells in the perilesional area as compared with other groups. DiscussionThe combination drug treatment of mannitol and temozolomide allowed for the efficient delivery of hUC-MSC–derived microvesicles into the brain in a chronic stroke rat model. This attenuated behavioral deficits, likely by improving neural regeneration and angiogenesis. Thus, combination drug treatment of mannitol and temozolomide could be a novel therapeutic option for patients with chronic ischemic stroke.

Bone Marrow-Derived Stem Cells Protect against Haloperidol-Induced Brain and Liver Damage in Mice

We studied the effect of bone marrow-derived stem cells (BM-SCs) on oxidative stress, inflammation and pathological changes induced in the brain and liver of mice by the antipsychotic drug haloperidol. Mice were intraperitoneally (i.p.) treated with haloperidol at 5 mg/kg for 3 consecutive days followed by i.p. stem cell suspension and euthanized 24h later. Haloperidol resulted in increased brain and liver malondialdehyde (MDA) and nitric oxide contents together with decreased reduced glutathione (GSH). There were also decreased paraoxonase-1 (PON-1) activity in brain and liver and increased interleukin-1β (IL-1 β), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in brain tissue. Haloperidol produced neuronal necrosis and apoptosis and the appearance of esinophilic areas and strong TNF-α immunoreactivity in the cerebral cortex and striatum of treated mice. In the liver, centrilobular necrosis, inflammatory cell infiltration and sinusoidal haemorrhage were observed. In haloperidol-treated mice, stem cell injection had no significant effects on brain and liver levels of MDA, nitric oxide or GSH. Paraoxonase-1 activity in brain, however, decreased by stem cells application. In brain, there were decreased IL-1β, IL-6 and TNF-α. Brain neurodegenerative changes, brain TNF-immunoreactivity and histological liver damage were all markedly ameliorated after stem cell treatment. These results indicate that stem cells protect against brain and liver toxicity caused by short term haloperidol treatment in high dose. The protective effects of stem cell treatment is likely to result from interfering with cytokine release.

A Comparison of Health Outcomes in the Use of Stem Cells, Surgical, and Nonsurgical Approaches to Treat Degenerative Disk Disease: A Systematic Review

Study design:Systematic literature review.Objective:This study provided a systematic review of randomized controlled trials which assessed the therapeutic effects of stem cell treatments, surgical ...

Effects of Stem Cell Treatment in Human Patients With Peyronie Disease.

Peyronie disease (PD) is a connective tissue disorder involving the formation of fibrous plaques in the tunica albuginea. Abnormal plaques and scar tissue create a chronic state of inflammation, causing increased curvature of the penis as well as erectile dysfunction. To determine the feasibility and effects of using placental matrix-derived mesenchymal stem cells (PM-MSCs) in the management of PD. In a prospective study, patients with PD were injected with PM-MSCs, and followed up at 6-week, 3-month, and 6-month intervals to assess changes in plaque volume, penile curvature, and erectile function status (measured using peak systolic velocity, end-diastolic velocity, and the International Index of Erectile Function questionnaire). In the 5 patients enrolled in the study, statistically significant increases in peak systolic velocity occurred after PM-MSC injection (P<.01). Of a total of 10 plaques managed, 7 had disappeared completely at 3-month follow-up. Changes in end-diastolic velocity, stretched penile length, and penile girth were not statistically significant. To our knowledge, this study is the first on the use of stem cells to manage PD in humans. The results suggest that PM-MSCs may be beneficial and effective as a nonsurgical treatment in patients with PD. Future studies with long-term follow-up in a larger sample of patients are warranted. (ClinicalTrials.gov number NCT02395029).

The Effect of Intracoronary Stem Cell Injection on Markers of Leukocyte Activation in Acute Myocardial Infarction.

BackgroundBeneficial effects of stem cell treatment during acute myocardial infarction (AMI) have been suggested, but the effects on inflammation are controversial. The neutrophil cell markers pentraxin 3 (PTX3) and myeloperoxidase (MPO) are both reported to be elevated during AMI. We studied the effects of stem cell treatment in ST-elevation myocardial infarction (STEMI) on PTX3 and MPO levels.MethodsSubjects with STEMI undergoing percutaneous coronary intervention (PCI) were randomized to intracoronary injection of bone marrow cells (mBMCs) (n = 50) or controls (n = 50). Blood samples were drawn 1 day before mBMC injection (baseline), after 1 day, 3 days, 2 - 3 weeks and 3 months. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used for biochemical analysis. Myocardial necrosis was quantified by single photon emission computed tomography (SPECT) and creatine kinase MB (CKMB) levels.ResultsPTX3 and MPO levels did not differ between the groups at any time points. Within the mBMC group, overall changes in both variables were observed (P < 0.01), with decreased levels from baseline throughout. Within the control group, similar patterns were observed. The relative reduction of PTX3 from baseline to day 1 was significantly less pronounced in the mBMC group compared to controls (P = 0.002), whereas no differences in relative changes from baseline were observed for MPO. Plasma and gene expression levels of PTX3 in leukocytes correlated significantly at all time points (r = 0.379 - 0.448, P < 0.01, all). MPO was significantly correlated to baseline left ventricular ejection fraction (LVEF) (r = -0.229, P = 0.025) and peak CKMB (r = 0.200, P = 0.05).ConclusionsStem cell treatment had limited effect on plasma levels of PTX3 and MPO. The initially high PTX3 and MPO levels, the genetic regulation of PTX3 and the association between MPO and myocardial injury support the importance of neutrophil cell activation in STEMI.

P-31 * COMBINED APPLICATION OF DRUG AND STEM CELLS FOR TREATING ALCOHOL-INDUCED BRAIN DAMAGE AND DEPRESSION

In alcoholism and fetal alcohol spectrum disorder (FASD) research, alcohol exposure-induced disorders of neural circuit development and neuronal regeneration/degeneration are central to the pathology and clinical expression of these disorders. A number of in vitro and in vivo studies demonstrate the impact of neurogenesis impairment as the common mechanism in pathophysiology of alcoholism and other psychiatric disorders such as depression. Many researchers have suggested that antidepressant increased neurogenesis which was required for the behavioral effects and alcohol treatment decreased this function. Stem cell-based regenerative therapy promises great benefits for patients with incurable brain diseases. We studied the involvement of corticolimbic GABAergic interneuron disruption in cognitive and social impairment in FASD and its recovery effect of stem cell treatment. We created new rat model of refractory depression by combination of fetal (alcohol) and adolescent (corticosterone) period stress exposures. We have indicated that depressive behavior described in this model could be recovered by combined treatment of antidepressant with stem cells but not by antidepressant treatment alone. Our results suggest that alterations of neurogenesis function, especially GABA neuron production underlie the pathogenetic mechanism of alcohol-induced brain damage and depression and possible therapeutic mechanism of stem cell treatment combined with drug for these disorders.

Can Stem Cell Transplant Be a New Alternative in the Treatment of Schizophrenia?

Until recently, it was thought that there is no neuronal regeneration and neuron loss is irreversible, but today the existence of neural regeneration and neural plasticity have been documented. The effectiveness of stem cell treatment in numerous degenerative diseases, as well as some neurodegenerative diseases, has created hopes toward the use of stem cell treatment in schizophrenia, which is a disease that progresses with neuronal degeneration and loss of neurons, and is characterized with worsening clinical outcomes and impairment.