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Cureus Sep 2019Objective The effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem...
Objective The effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem cell therapy plus the standard of care as compared to the placebo plus the standard of care in advanced heart failure patients. Methods A comprehensive keyword search of PubMed between 2017 and 2019 was performed to extract trials conducted with stem cell therapy controlled with placebo in advanced heart failure. We included randomized controlled trials (RCTs) with data on safety and efficacy in patients with advanced heart failure after stem cell transplantation. Results Six RCTs, consisting of 569 patients, were selected. Three-hundred sixty-seven (367) out of 369 participants from the eligible four out of six RCTs were included for efficacy analysis, as we lost two patients from the final analysis due to early death. Five-hundred twenty-six (526) out of 527 participants from the eligible five out of six RCTs were included for safety analysis, as we lost one patient from the final analysis for not being able to receive the intervention. Stem cell transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.58% (95% CI: 3.73-5.43%; p = 0.00001), improved left ventricular end-systolic volume (LVESV) by -5.18 ml (95% CI: -9.74 to -0.63 ml; p =0.03), and there was no difference in the risk of all-cause mortality (OR 0.97; 95% CI: 0.52 to 1.78%; p = 0.91). The above results correlate with the previous meta-analysis data conducted in 2016. Conclusions This meta-analysis provided the cumulative efficacy and safety results of stem cell transplantation in advanced heart failure based on recent RCTs. The above results suggest that stem cell therapy was associated with a moderate improvement in LVEF, and the safety analysis indicates no increased risk of mortality in patients with advanced heart failure. This meta-analysis recommends conducting more RCTs comparing stem cell transplantation and placebo with a larger patient population and longer follow-up.
PubMed: 31696004
DOI: 10.7759/cureus.5585 -
World Journal of Gastroenterology Apr 2019Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also...
Understanding the occurrence, development, and treatment of liver diseases is the main goal of hepatopathology research. Liver diseases are not only diverse but also highly heterogeneous among individuals. At present, research on liver diseases is conducted mainly through cell culture, animal models, pathological specimens, . However, these methods cannot fully reveal the pathogenic mechanism and therapeutic characteristics of individualized liver diseases. Recent advances in three-dimensional cell culture technology (organoid culture techniques) include pluripotent stem cells and adult stem cells that are cultured to form self-organizing properties, making it possible to achieve individualized liver disease research. This review provides a comprehensive overview of the development of liver organoids, the existing and potential applications of liver regenerative medicine, the pathogenesis of liver disease heterogeneity, and drug screening.
Topics: Animals; Cell Culture Techniques; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Liver; Liver Diseases; Organoids; Regenerative Medicine; Translational Research, Biomedical
PubMed: 31086460
DOI: 10.3748/wjg.v25.i16.1913 -
Stem Cells Translational Medicine Jul 2019Induced pluripotent stem cells (iPSCs) are cells genetically reprogrammed from somatic cells, which can be differentiated into neurological lineages with the aim to... (Meta-Analysis)
Meta-Analysis
Induced pluripotent stem cells (iPSCs) are cells genetically reprogrammed from somatic cells, which can be differentiated into neurological lineages with the aim to replace or assist damaged neurons in the treatment of spinal cord injuries (SCIs) caused by physical trauma. Here, we review studies addressing the functional use of iPSC-derived neural cells in SCIs and perform a meta-analysis to determine if significant motor improvement is restored after treatment with iPSC-derived neural cells compared with treatments using embryonic stem cell (ESC)-derived counterpart cells and control treatments. Overall, based on locomotion scales in rodents and monkeys, our meta-analysis indicates a therapeutic benefit for SCI treatment using neural cells derived from either iPSCs or ESCs, being this of importance due to existing ethical and immunological complications using ESCs. Results from these studies are evidence of the successes and limitations of iPSC-derived neural cells in the recovery of motor capacity. Stem Cells Translational Medicine 2019;8:681&693.
Topics: Animals; Cell Differentiation; Human Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Neural Stem Cells; Recovery of Function; Spinal Cord Injuries
PubMed: 30903654
DOI: 10.1002/sctm.18-0225 -
Pflugers Archiv : European Journal of... May 2019Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human...
Human-induced pluripotent stem cells (hiPSC) can be differentiated to cardiomyocytes at high efficiency and are increasingly used to study cardiac disease in a human context. This review evaluated 38 studies on hypertrophic (HCM) and dilated cardiomyopathy (DCM) of different genetic causes asking to which extent published data allow the definition of an in vitro HCM/DCM hiPSC-CM phenotype. The data are put in context with the prevailing hypotheses on HCM/DCM dysfunction and pathophysiology. Relatively consistent findings in HCM not reported in DCM were larger cell size (156 ± 85%, n = 15), more nuclear localization of nuclear factor of activated T cells (NFAT; 175 ± 65%, n = 3), and higher β-myosin heavy chain gene expression levels (500 ± 547%, n = 8) than respective controls. Conversely, DCM lines showed consistently less force development than controls (47 ± 23%, n = 9), while HCM forces scattered without clear trend. Both HCM and DCM lines often showed sarcomere disorganization, higher NPPA/NPPB expression levels, and arrhythmic beating behaviour. The data have to be taken with the caveat that reporting frequencies of the various parameters (e.g. cell size, NFAT expression) differ widely between HCM and DCM lines, in which data scatter is large and that only 9/38 studies used isogenic controls. Taken together, the current data provide interesting suggestions for disease-specific phenotypes in HCM/DCM hiPSC-CM but indicate that the field is still in its early days. Systematic, quantitative comparisons and robust, high content assays are warranted to advance the field.
Topics: Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Mutation; Myocardial Contraction; Myocytes, Cardiac; Phenotype
PubMed: 30324321
DOI: 10.1007/s00424-018-2214-0 -
Cellular Physiology and Biochemistry :... 2018Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function... (Meta-Analysis)
Meta-Analysis Review
Induced Pluripotent Stem Cell Transplantation Improves Locomotor Recovery in Rat Models of Spinal Cord Injury: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND/AIMS
Spinal cord injury (SCI) has long been a subject of great interest in a wide range of scientific fields. Several attempts have been made to demonstrate motor function improvement in rats with SCI after transplantation of induced pluripotent stem cells (iPSC). This systematic review and meta-analysis was designed to summarize the effects of iPSC on locomotor recovery in rat models of SCI.
METHODS
We searched the publications in the PubMed, Medline, Science Citation Index, Cochrane Library, CNKI, and Wan-fang databases and the China Biology Medicine disc. Results were analyzed by Review Manager 5.3.0. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.
RESULTS
Six randomized controlled preclinical trials covering eight comparisons and including 212 rats were selected. The subgroup analyses were based on the following items: different SCI models, cell counts, iPSC sources, iPSC differentiations and transplantation methods. The pooled results indicated that iPSC transplantation significantly improved locomotor recovery of rats after SCI by sustaining beneficial effects, especially in the subgroups of contusion, moderate cell counts (5×105), source of human fetal lung fibroblasts, iPSC-neural precursors and intraspinal injection.
CONCLUSION
Our meta-analysis of the effects of iPSC transplantation on locomotor function in SCI models is, to our knowledge, the first meta-analysis in this field. We conclude that iPSC transplantation improves locomotor recovery in rats with SCI, implicating this strategy as an effective therapy. However, more studies are required to validate our conclusions.
Topics: Animals; Disease Models, Animal; Induced Pluripotent Stem Cells; Locomotion; Rats; Recovery of Function; Spinal Cord Injuries; Stem Cell Transplantation
PubMed: 29961052
DOI: 10.1159/000491064 -
Journal of Ophthalmology 2018Diabetic retinopathy (DR) is classically defined by its vascular lesions and damage in the neurons of the retina. The cellular and clinical elements of DR have many... (Review)
Review
Diabetic retinopathy (DR) is classically defined by its vascular lesions and damage in the neurons of the retina. The cellular and clinical elements of DR have many features of chronic inflammation. Understanding the individual cell-specific inflammatory changes in the retina may lead to novel therapeutic approaches to prevent vision loss. The systematic use of available pharmacotherapy has been reported as a useful adjunct tool to laser photocoagulation, a gold standard therapy for DR. Direct injections or intravitreal anti-inflammatory and antiangiogenesis agents are widely used pharmacotherapy to effectively treat DR and diabetic macular edema (DME). However, their effectiveness is short term, and the delivery system is often associated with adverse effects, such as cataract and increased intraocular pressure. Further, systemic agents (particularly hypoglycemic, hypolipidemic, and antihypertensive agents) and plants-based drugs have also provided promising treatment in the progression of DR. Recently, advancements in pluripotent stem cells technology enable restoration of retinal functionalities after transplantation of these cells into animals with retinal degeneration. This review paper summarizes the developments in the current and potential pharmacotherapy and therapeutic technology of DR. Literature search was done on online databases, PubMed, Google Scholar, clinitrials.gov, and browsing through individual ophthalmology journals and leading pharmaceutical company websites.
PubMed: 29576875
DOI: 10.1155/2018/1694187 -
Biomedical Reports Mar 2018The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies....
The effects of induced pluripotent stem cells (iPSCs) in 6-hydroxydopamine-lesioned rat models of Parkinson's disease (PD) have been evaluated in multiple studies. However, the results evaluating the effectiveness of iPSCs in animal models of PD are mixed, primarily due to their low statistical power. In the current study, a meta-analysis was performed to describe the treatment effect of unsorted iPSCs on behavioral testing in experimental rat models of PD. Databases searched included PubMed, EMBASE, MEDLINE and the Cochrane Library from inception to March 2017. Data were extracted for rotation behavior tests (induced by amphetamine and apomorphine) and limb function tests. A total of eight studies were included in the current meta-analysis, and iPSCs were identified to be efficacious according to the pooled standardized mean differences (SMDs) for improving amphetamine-induced rotational behavior [SMD, -2.16; 95% confidence interval (95% CI), -2.93, -1.40; P<0.00001] and apomorphine-induced rotational test (SMD, -1.45; 95% CI, -2.16, -0.73; P<0.0001). The pooled evidence indicated that iPSCs improve rotational behavior in rat models of PD. It was concluded that iPSCs provide a potential approach for developing novel treatment strategies for PD, and the results of this meta-analysis may guide future preclinical and clinical studies.
PubMed: 29564126
DOI: 10.3892/br.2018.1049 -
Cell Proliferation Apr 2017Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation... (Review)
Review
OBJECTIVES
Mesenchymal stem cells (MSCs) are frequently used for bone regeneration, however, they are limited in quantity. Moreover, their proliferation and differentiation capabilities reduce during cell culture expansion. Potential application of induced pluripotent stem cells (iPSCs) has been reported as a promising alternative source for bone regeneration. This study aimed to systematically review the available literature on osteogenic potential of iPSCs and to discuss methods applied to enhance their osteogenic potential.
METHODS AND MATERIALS
A thorough search of MEDLINE database was performed from January 2006 to September 2016, limited to English-language articles. All in vitro and in vivo studies on application of iPSCs in bone regeneration were included.
RESULTS
The current review is organized according to the PRISMA statement. Studies were categorized according to three different approaches used for osteo-induction of iPSCs. Data are summarized and reported according to the following variables: types of study, cell sources used for iPSC generation, applied reprogramming methods, applied osteo-induction methods and treatment groups.
CONCLUSION
According to the articles reviewed, osteo-induced iPSCs revealed osteogenic capability equal to or superior than MSCs; cell sources do not significantly affect osteogenic potential of iPSCs; addition of resveratrol to the osteogenic medium (OM) and irradiatiation after osteogenic induction reduce teratoma formation in animal models; transfection with lentiviral bone morphogenetic protein 2 results in higher mineralization compared to osteo-induction in OM; addition of TGF-β, IGF-1 and FGF-β to OM increases osteogenic capability of iPSCs.
Topics: Animals; Bone and Bones; Cell Differentiation; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Osteogenesis; Tissue Engineering
PubMed: 27905670
DOI: 10.1111/cpr.12321 -
Stem Cells Translational Medicine Dec 2015Idiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much... (Review)
Review
UNLABELLED
Idiopathic pulmonary fibrosis is an inexorably progressive lung disease with few available treatments. New therapeutic options are needed. Stem cells have generated much enthusiasm for the treatment of several conditions, including lung diseases. Human trials of mesenchymal stromal cell (MSC) therapy for pulmonary fibrosis are under way. To shed light on the potential usefulness of MSCs for human disease, we aimed to systematically review the preclinical literature to determine if MSCs are beneficial in animal bleomycin pulmonary fibrosis models. The MEDLINE and Embase databases were searched for original studies of stem cell therapy in animal bleomycin models of pulmonary fibrosis. Studies using embryonic stem cells or induced pluripotent stem cells were excluded. Seventeen studies were selected, all of which used MSCs in rodents. MSC therapy led to an improvement in bleomycin-induced lung collagen deposition in animal lungs and in the pulmonary fibrosis Ashcroft score in most studies. MSC therapy improved histopathology in almost all studies in which it was evaluated qualitatively. Furthermore, MSC therapy was found to improve 14-day survival in animals with bleomycin-induced pulmonary fibrosis. Bronchoalveolar lavage total and neutrophil counts, as well as transforming growth factor-β levels, were also reduced by MSCs. MSCs are beneficial in rodent bleomycin pulmonary fibrosis models. Since most studies examined the initial inflammatory phase rather than the chronic fibrotic phase, preclinical data offer better support for human trials of MSCs in acute exacerbations of pulmonary fibrosis rather than the chronic phase of the disease.
SIGNIFICANCE
There has been increased interest in mesenchymal stromal cell therapy for lung diseases. A few small clinical trials are under way in idiopathic pulmonary fibrosis. Preclinical evidence was assessed in a systematic review, as is often done for clinical studies. The existing studies offer better support for efficacy in the initial inflammatory phase rather than the fibrotic phase that human trials are targeting.
Topics: Animals; Bleomycin; Disease Models, Animal; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Pulmonary Fibrosis
PubMed: 26494779
DOI: 10.5966/sctm.2015-0121 -
International Wound Journal Dec 2016Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that... (Review)
Review
Wound healing is an articulated process that can be impaired in different steps in chronic wounds. Chronic leg ulcers are a special type of non-healing wounds that represent an important cause of morbidity and public cost in western countries. Because of their common recurrence after conventional managements and increasing prevalence due to an ageing population, newer approaches are needed. Over the last decade, the research has been focused on innovative treatment strategies, including stem-cell-based therapies. After the initial interest in embryonic pluripotent cells, several different types of adult stem cells have been studied because of ethical issues. Specific types of adult stem cells have shown a high potentiality in tissue healing, in both in vitro and in vivo studies. Aim of this review is to clearly report the newest insights on tissue regeneration medicine, with particular regard for chronic leg ulcers.
Topics: Adult; Chronic Disease; Female; Humans; Leg Ulcer; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Prognosis; Regeneration; Role; Severity of Illness Index; Wound Healing
PubMed: 26399452
DOI: 10.1111/iwj.12499