Effect Of Stem Cell Transplantation Research Articles

Abstract 15233: Stem Cell Therapy for the Treatment of Chronic Ischemic Heart Disease: A Review

Introduction: Chronic ischemic heart disease remains a major cause of morbidity and mortality. Several clinical trials have been performed to evaluate benefit of stem cells transplantation to restore cardiac function. Aim: The review reports potential benefit of stem cells therapy in chronic ischemic heart disease. Methods: Trials were selected applying as search terms “bone marrow cells”, “stem cells”, “mesenchymal cells”, and “chronic ischemic heart disease” in www.pubmed.gov and Cochrane library from 2005 to 2023. Studies were included if they were randomized blinded trials, randomized unblinded trials, non-randomized trials. Left ventricular ejection fraction (LVEF) increase and New York Heart Association (NYHA) class decrease were the outcome parameters at 6 and 12 months follow up. Results: We analyzed 20 trials including 1812 patients (939 treated, 789 males, mean age 62 years). Bone marrow (BMC), peripheral blood (PBC), cardiac (CDC) or mesenchymal (MES) stem cells were utilized in 8, 5, 7 trials, respectively. Total number of transplanted cells ranged from 5 x 10 6 to 1,300 x 10 6 (median 70 x 10 6 ) depending on cell type, cell population purification, and transplantation route. Transplant procedure was intracoronary in 9 trials and intramyocardial in 11 trials. At baseline mean LVEF was 33.5 % (range 27.1 - 46.0 %). Eleven trials reported a statistically significant percent LVEF increase between 4% to 19% (mean 9.6%) at 12 months after stem cells transplantation ( p values ranging from 0.05 to 0.001). BMC and PBC stem cells were utilized in all these studies. A significant correlation was found between number of transplanted cells and percent LVEF increase (Pearson correlation coefficient 0.74, p = 0.01). Conclusions: Results seem to favor a moderate positive effect of stem cells transplantation in chronic ischemic heart disease at 12 months follow up. The positive effect was correlated with the number of transplanted cells. However, caution should be exercised in the evaluation of clinical trials due to the different stem cells utilized, transplant protocols and endpoints.

Nitrosylation of β2-Tubulin Promotes Microtubule Disassembly and Differentiated Cardiomyocyte Beating in Ischemic Mice.

Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of β2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. Tyr-NO-β2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-β2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. This is the first discovery of a new target molecule of NO, β2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-β2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Clinical effect of stem cell transplantation combined with 308-nm excimer laser therapy for 56 cases of vitiligo.

To probe the clinical effect of stem cell transplantation in combination with 308-nm excimer laser therapy for vitiligo and to analyze its value in clinical application. A total of 56 patients with stable non-segmental vitiligo in different parts who were not cured by other therapies visiting our hospital from March 2019 to December 2021 were enrolled as study subjects. They were treated by stem cell transplantation combined with 308-nm excimer laser therapy. The treatment efficacy was observed and analyzed. Among the 56 patients, 38 (67.85%) and 49 (87.5%) patients were cured at 6 and 12 months after treatment, respectively. Stem cell transplantation combined with 308-nm excimer laser therapy for vitiligo achieves significant efficacy, with the cure rate far superior to that of other therapies for vitiligo. The therapy is worthy of popularization in the clinic.

Advances in stem cell transplantation for traumatic spinal cord injury at different stages

To summarize the research progress of stem cell transplantation in treating spinal cord injury (SCI) at different stages based on the pathophysiological mechanism of SCI. The relevant research literature at home and abroad was extensively reviewed to explore the impact of transplantation timing on the effectiveness of stem cell transplantation in treating SCI. Researchers performed different types of stem cell transplantation for subjects at different stages of SCI through different transplantation approaches. Clinical trials have proved the safety and feasibility of stem cell transplantation at acute, subacute, and chronic stages, which can alleviate inflammation at the injured site and restore the function of the damaged nerve cells. But the reliable clinical trials comparing the effectiveness of stem cell transplantation at different stages of SCI are still lacking. Stem cell transplantation has a good prospect in treating SCI. In the future, the multi-center, large sample randomized controlled clinical trials are needed, with a focus on the long-term effectiveness of stem cell transplantation.

Comparison of the Anti-Inflammatory Effects of Mouse Adipose- and Bone-Marrow-Derived Multilineage-Differentiating Stress-Enduring Cells in Acute-Phase Spinal Cord Injury.

Abstract Spinal cord injury (SCI) is a serious neurological disorder, with the consequent disabilities conferred by this disorder typically persisting for life. Multilineage-differentiating stress-enduring (Muse) cells are endogenous stem cells that can be collected from various tissues as well as from mesenchymal stem cells (MSCs); additionally, these Muse cells are currently being used in clinical trials. The anti-inflammatory effect of stem cell transplantation prevents secondary injuries of SCI; however, its effect on Muse cells remains unclear. In this study, we aimed to compare the anti-inflammatory effects of adipose (AD)- and bone marrow (BM)-Muse cells that were isolated from mice (6-week-old C57BL/6J) following intralesional administration during the acute phase of SCI. Flow cytometry was used to isolate Muse cells from AD and BM MSCs. The percentage of Muse cells was 3.9 and 2.7% for AD and BM MSCs, respectively. To examine cell viability, Muse cells were incubated under H2O2-induced oxidative stress conditions. Overall, AD-Muse cells exhibited higher viability than BM-Muse cells (p = 0.032). In enzyme-linked immunosorbent assay analysis, AD-Muse cells displayed greater secretion of brain-derived neurotrophic factor (BDNF; p = 0.008), vascular endothelial growth factor (p = 0.032), and hepatocyte growth factor (p = 0.016). DNA microarray analysis revealed higher expression of Bdnf, neurotrophin-3 (Ntf3), nerve growth factor (Ngf), pleiotrophin (Ptn), and midkine (Mdk) in AD-Muse cells than in BM-Muse cells. To assess their anti-inflammatory effects in vitro, Muse cells and macrophages were co-cultured, and the levels of cytokines (tumor necrosis factor [TNF] α and interleukin [IL] 10) were measured in the medium. Consequently, we found that TNFα levels were lower in AD-Muse cells than in BM-Muse cells (p = 0.009), and IL10 levels were higher in AD-Muse cells than in BM-Muse cells (p = 0.008). Further, we induced moderate injuries via contusion of the spinal cord at the T10 level; Muse cells were transplanted intralesionally 7 days post-SCI. The number of surviving cells, alongside the number of CD86+ (M1 inflammatory effect), and CD206+ (M2 anti-inflammatory effect) macrophages in the spinal cord were measured 7 days post-transplantation. The number of surviving AD-Muse cells was higher than the number of surviving BM-Muse cells (ratio of AD-Muse/BM-Muse = 2.5, p > 0.05). The M1/M2 ratio in the AD-Muse cell-group (0.37) was lower than that in the control (phosphate-buffered saline) group (3.60, p = 0.008). The lesion area in the AD-Muse cell group was smaller than that in the BM-non-Muse (p = 0.049) and control groups (p = 0.012). As AD-Muse cells conferred a higher cell survival and neurotrophic factor secretion ability in vitro, AD-Muse cells demonstrated reduced inflammation after SCI. Overall, intralesional AD-Muse cell therapy is a potential therapeutic candidate that is expected to exhibit anti-inflammatory effects following acute SCI.

Efficacy of Cellular Therapy for Azoospermia in Animal Models: A Systematic Review and Meta-Analysis

This study investigated the efficacy of stem cell transplantation for azoospermia, a major cause of male infertility. We conducted a systematic meta- analysis to assess the therapeutic effectiveness of stem cell transplant, using different transplant methods, injection sites, and stem cell types, and the reliability of this approach in different animal species. PubMed, the Cochrane Library, and Embase were searched for studies published from January 2006 to February 2022 that evaluated the use of stem cell transplant to treat azoospermia. We included 18 studies and conducted the analyses using Review Manager 5.2 software. Expression of the meiosis-related genes Vasa, Scp3, and Dazl and the average hematoxylin and eosin- positive staining area were improved after stem cell transplant. Subgroup analyses by mode of transplant showed higher expression of Scp3 and Dazl in the xenotransplant group. Although subgroup analyses by injection site showed that the seminiferous tubule group showed the most significant effect on Scp3 expression, spermatogenesis and repair of damaged testis were induced in the tunica albuginea group. The testicular torsion group also induced high levels of Scp3. Another subgroup analysis by stem cell type showed that umbilical cord mesenchymal stem cells promoted the highest expression of meiosis-related genes and successfully induced spermatogenesis and the repair of damaged testis. Urine-derived stem cells, spermatogonial stem cells, and amniotic fluid-derived stem cells showed significantly therapeutic effects; however, more studies are needed for definitive conclusions. Subgroup analyses by type of azoospermia animal model indicated that the use of stem cell transplant in rat or mouse models had an obvious therapeutic effect, but no significant therapeutic effect was seen in azoospermia hamsters. The meta-analysis confirmed that stem cell transplant can effectively treat azoospermia in animal models. Xenotransplant is shown to enhance the therapeutic effects of stem cell transplant on azoospermia.

Stem cell therapy of myocarditis and cardiomyopathies: a promising strategy

The literature review is devoted to the analysis of modern data on the effectiveness of stem cell transplantation in patients with non-coronary heart diseases: myocarditis, dilated cardiomyopathy, and systemic amyloidosis with heart damage. The results of experimental studies on laboratory animals and clinical trials concerning the use of various types of stem cells, their mechanisms of action and prospects for application in non-coronary heart diseases are presented. Emphasis is placed on the need for further randomized multicenter clinical trials, especially in patients with inflammatory myocardial injury, involving a large number of patients.

Stem Cell-Based Therapies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, relapsing disease that severely affects patients’ quality of life. The exact cause of IBD is uncertain, but current studies suggest that abnormal activation of the immune system, genetic susceptibility, and altered intestinal flora due to mucosal barrier defects may play an essential role in the pathogenesis of IBD. Unfortunately, IBD is currently difficult to be wholly cured. Thus, more treatment options are needed for different patients. Stem cell therapy, mainly including hematopoietic stem cell therapy and mesenchymal stem cell therapy, has shown the potential to improve the clinical disease activity of patients when conventional treatments are not effective. Stem cell therapy, an emerging therapy for IBD, can alleviate mucosal inflammation through mechanisms such as immunomodulation and colonization repair. Clinical studies have confirmed the effectiveness of stem cell transplantation in refractory IBD and the ability to maintain long-term remission in some patients. However, stem cell therapy is still in the research stage, and its safety and long-term efficacy remain to be further evaluated. This article reviews the upcoming stem cell transplantation methods for clinical application and the results of ongoing clinical trials to provide ideas for the clinical use of stem cell transplantation as a potential treatment for IBD.

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.

Stem cell transplantation for induction of remission in medically refractory Crohn's disease.

Stem cell transplantation for induction of remission in medically refractory Crohn's disease.

Distinct Effects of the Hippocampal Transplantation of Neural and Mesenchymal Stem Cells in a Transgenic Model of Alzheimer’s Disease

Alzheimer's disease (AD) is a severe disabling conditionwith no cure currently available, which accounts for 60-70% of all dementia cases worldwide. Therefore, the investigation of possible therapeutic strategies for AD is necessary. To this end, animal models corresponding to the main aspects of AD in humans have been widely used. Similar to AD patients, the double transgenic APPswe/PS1dE9 (APP/PS1) mice show cognitive deficits, hyperlocomotion, amyloid-β (Αβ) plaques in the cortex and hippocampus, and exacerbated inflammatory responses. Recent studies have shown that these neuropathological features could be reversed by stem cell transplantation. However, the effects induced by neural (NSC) and mesenchymal (MSC) stem cells has never been compared in an AD animal model. Therefore, the present study aimed to investigate whether transplantation of NSC or MSC into the hippocampus of APP/PS1 mice reverses AD-induced pathological alterations, evaluated by the locomotor activity (open field test), short- and long-term memory (object recognition) tests, Αβ plaques (6-E10), microglia distribution (Iba-1), M1 (iNOS) and M2 (ARG-1) microglial phenotypefrequencies. NSC and MSC engraftment reduced the number ofΑβ plaques and produced an increase in M2 microglia polarization in the hippocampus of APP/PS1 mice, suggesting an anti-inflammatory effect of stemcell transplantation. NSC also reversed the hyperlocomotor activity and increased the number of microglia in the hippocampus of APP/PS1 mice. No impairment of short or long-term memory was observed in APP/PS1 mice. Overall, this study highlights the potential beneficial effects of transplanting NSC or MSC for AD treatment.

Regulation of Stem Cell Differentiation by Inorganic Nanomaterials: Recent Advances in Regenerative Medicine.

Transplanting stem cells with the abilities of self-renewal and differentiation is one of the most effective ways to treat many diseases. In order to optimize the therapeutic effect of stem cell transplantation, it is necessary to intervene in stem cell differentiation. Inorganic nanomaterials (NMs), due to their unique physical and chemical properties, can affect the adhesion, migration, proliferation and differentiation of stem cells. In addition, inorganic NMs have huge specific surface area and modifiability that can be used as vectors to transport plasmids, proteins or small molecules to further interfere with the fate of stem cells. In this mini review, we summarized the recent advances of common inorganic NMs in regulating stem cells differentiation, and the effects of the stiffness, size and shape of inorganic NMs on stem cell behavior were discussed. In addition, we further analyzed the existing obstacles and corresponding perspectives of the application of inorganic NMs in the field of stem cells.

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis.

Objective Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats. Methods PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017. Results Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01, 95% CI: [1.38, 2.63], P < 0.001, I2 = 76.6%; ADSCs: SMD = 2.24, 95% CI: [0.79, 3.69], P = 0.003, I2 = 86.7%) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71, 95% CI: [0.97, 2.44], P < 0.001, I2 = 0%; ADSCs: SMD = 2.16, 95% CI: [0.27, 4.04], P = 0.025, I2 = 82.6%). In the BMSC treatment groups, the trabecular numbers (Tb.N) (SMD = 4.28, 95% CI: [0.91, 7.64], P = 0.013, I2 = 94.9%) were significantly higher, whereas the results for trabecular thickness (Tb.Th) (SMD = 2.7, 95% CI: [-0.34, 5.73], P = 0.081, I2 = 95.4%) and trabecular spacing (Tb.Sp) (SMD = −3.08, 95% CI: [-6.55, 0.38], P = 0.081, I2 = 96.3%) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group. Conclusion Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.

Stem Cell Transplantation Efficacy in Cerebral Palsy: A Physical Therapist Perspective

Background and Purpose&#x0D; Children with spastic cerebral palsy usually display elevation in muscle tone, a decline in gross motor functional abilities , feeding problems and sometimes it may accompanied by visual problems. Studies on stem cell treatment are in their early stages concerning their effect on cerebral palsy. &#x0D; Methods &#x0D; A child with spastic cerebral palsy on level v on gross motor function classification system was selected for autologous bone marrow derived mononuclear transplantation cell. Muscle tone, gross, fine motor abilities, feeding abilities and visual abilities were assessed on 4 occasions, prior the transplantation, immediately after the transplantation, after 6 months and after 1 year.&#x0D; Results No effect of stem cell transplantation was shown on the child.&#x0D; Conclusion Further research studies should be done on the subject but using different population rather than children on level V Gross motor function classification system

Methyltransferase-like protein 7A (METTL7A) promotes cell survival and osteogenic differentiation under metabolic stress

While bone has an inherent capacity to heal itself, it is very difficult to reconstitute large bone defects. Regenerative medicine, including stem cell implantation, has been studied as a novel solution to treat these conditions. However, when the local vascularity is impaired, even the transplanted cells undergo rapid necrosis before differentiating into osteoblasts and regenerating bone. Thus, to increase the effectiveness of stem cell transplantation, it is quintessential to improve the viability of the implanted stem cells. In this study, given that the regulation of glucose may hold the key to stem cell survival and osteogenic differentiation, we investigated the molecules that can replace the effect of glucose under ischemic microenvironment of stem cell transplantation in large bone defects. By analyzing differentially expressed genes under glucose-supplemented and glucose-free conditions, we explored markers such as methyltransferase-like protein 7A (METTL7A) that are potentially related to cell survival and osteogenic differentiation. Overexpression of METTL7A gene enhanced the osteogenic differentiation and viability of human bone marrow stem cells (hBMSCs) in glucose-free conditions. When the in vivo effectiveness of METTL7A-transfected cells in bone regeneration was explored in a rat model of critical-size segmental long-bone defect, METTL7A-transfected hBMSCs showed significantly better regenerative potential than the control vector-transfected hBMSCs. DNA methylation profiles showed a large difference in methylation status of genes related to osteogenesis and cell survival between hBMSCs cultured in glucose-supplemented condition and those cultured in glucose-free condition. Interestingly, METTL7A overexpression altered the methylation status of related genes to favor osteogenic differentiation and cell survival. In conclusion, it is suggested that a novel factor METTL7A enhances osteogenic differentiation and viability of hBMSCs by regulating the methylation status of genes related to osteogenesis or survival.

DNA and modified vaccinia Ankara prime-boost vaccination generates strong CD8+ T cell responses against minor histocompatibility antigen HA-1.

Allogeneic immune responses underlie the graft-versus-leukaemia effect of stem cell transplantation, but disease relapse occurs in many patients. Minor histocompatibility antigen (mHAg) peptides mediate alloreactive T cell responses and induce graft-versus-leukaemia responses when expressed on patient haematopoietic tissue. We vaccinated nine HA-1-negative donors against HA-1 with a 'prime-boost' protocol of either two or three DNA 'priming' vaccinations prior to 'boost' with modified vaccinia Ankara (MVA). HA-1-specific CD8+ T cell responses were observed in seven donors with magnitude up to 1·5% of total CD8+ T cell repertoire. HA-1-specific responses peaked two weeks post-MVA challenge and were measurable in most donors after 12months. HA-1-specific T cells demonstrated strong cytotoxic activity and lysed target cells with endogenous HA-1 protein expression. The pattern of T cell receptor (TCR) usage by HA-1-specific T cells revealed strong conservation of T cell receptor beta variable 7-9 (TRBV7-9) usage between donors. These findings describe one of the strongest primary peptide-specific CD8+ T cell responses yet recorded to a DNA-MVA prime-boost regimen and this may reflect the strong immunogenicity of mHAg peptides. Prime-boost vaccination in donors or patients may prove of substantial benefit in boosting graft-versus-leukaemia responses.

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review.

Stem cell transplantation offers promise in the treatment of ischemic stroke. Here we utilized systematic review, meta-analysis, and meta-regression to study the biological effect of stem cell treatments in animal models of ischemic stroke. A total of 98 eligible publications were included by searching PubMed, EMBASE, and Web of Science from inception to August 1, 2020. There are about 141 comparisons, involving 5,200 animals, that examined the effect of stem cell transplantation on neurological function and infarct volume as primary outcome measures in animal models for stroke. Stem cell-based therapy can improve both neurological function (effect size, −3.37; 95% confidence interval, −3.83 to −2.90) and infarct volume (effect size, −11.37; 95% confidence interval, −12.89 to −9.85) compared with controls. These results suggest that stem cell therapy could improve neurological function deficits and infarct volume, exerting potential neuroprotective effect for experimental ischemic stroke, but further clinical studies are still needed.

Gross Motor Functioning in Children with Cerebral Palsy after Stem Cell Transplantation

Background Cerebral palsy (CP) is a non-progressive motor disability that mostly results from perinatal complications. It demands extensive and multidisciplinary care, which poses a burden for patients and their families and a challenge to health systems. We aimed to evaluate the effect of stem cells transplantation on gross motor functioning of CP patients. Patients and Methods: It is a prospective study conducted on 20 children diagnosed with cerebral palsy with severe motor disability (GMFC 5) further classified into two groups according to age. The study was carried out from January 2018 to January 2020. Follow up of the patients was done before injection of stem cells and 3, 6, 9 and 12 months after injection of stem cells using Gross motor function classification scale (GMFC). Results: The study revealed that GMFC scores in pre-injection and 3,6,9and 12 months evaluations were not statistically significant when compared among the two groups while significant improvement was found in gross motor scale from pre-injection to final injection score in each group. Median GMFC changed from 5 to 2 among all cases. Conclusion: Gross motor function in children with CP remarkably improved after stem cell transplantation.

A compressive mathematical model including an eclipse stage of infected cells to study the impact of stem cells transplantation on one HIV1 patient

We propose a new mathematical model to study the effect of stem cells transplantation on HIV-1 patient as a system of first order nonlinear ordinary differential equations. We include in this model five populations: stem cells, free virus, productively infected cells, infected cells in the eclipse stage and non-infected T cells. The model admits two equilibrium states: a non-infected point and an endemically infected one. The study of the stability of the system before treatment is already known: If the “basic reproduction number” is smaller than 1, then the free disease point is asymptotically stable. If the “basic reproduction number” is greater than 1, then the endemic point is asymptotically stable. The study of the stability of the system after treatment proves that, for a patient with an initial “basic reproduction number”, greater than 1, if it is possible for the therapy to lower this ratio under 1, then the patient will recover. If it is not possible to lower the ratio under 1, the HIV infection persists, but, it is possible to offer to the patient a better life.

The Clinical Outcomes of Stem Cell Therapy for Decompensated Liver Disease: A Systematic Review and Meta-Analysis

Worldwide, many patients with decompensated liver disease cannot get timely liver transplantation due to the shortage of the liver donors. In this case, stem cell therapy seems to be an alternative for patients with end stage liver disease. The aim of this article is to conduct a meta-analysis to evaluate the effectiveness of stem cell transplantation in patients with decompensated liver disease. Medline, Embase and Cochrane Library were searched for relevant studies. Only controlled trials were enrolled in this meta-analysis. Random effect model or fixed effect model will be used to analyze the collected data depending on the heterogeneity of the pooled studies. Review Manager 5.3 was used for statistical analysis. 8 publications involving 9 controlled studies were included in the final analysis. The studies were conducted in China, Iran, Egypt and India. Cell transplantation did not change the level of serum albumin and model for end stage liver disease score at 12 w and 24 w. Furthermore, no matter at 12 w or 24 w, the serum level of total bilirubin showed statistical decline. However, alanine transaminase, aspartate transaminase and prothrombin activity were improved significantly at 12 w, but this change was not obvious at 24 w. Stem cell transplantation showed some desirable outcomes in a relatively short term. However, many hepatic parameters did not last in the long term. Further studies are needed to explore the efficacy in patients with decompensated liver disease.