Cell therapy for retinal degenerative disorders: a systematic review and three-level meta-analysis
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ABSTRACT:
SUBMITTER: Khaboushan A
PROVIDER: S-EPMC10908175 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesWe systematically reviewed randomized controlled trials (RCTs) of the effect of low-level laser therapy (LLLT) versus placebo in patients with temporomandibular disorder (TMD).MethodsA systematic search of multiple online sources electronic databases was undertaken. The methodological quality of each included study was assessed using the modified Jadad scale, and the quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.ResultsA total of 31 RCTs were included. Total modified Jadad scale scores showed that the methodological quality was high in 30 studies and low in 1 study. Combining data from all clinically heterogeneous studies revealed positive effects of LLLT on pain relief, regardless of the visual analogue scale (VAS) score or the change of VAS score between the baseline and the final follow-up time point, while dosage analyses showed discrepant results about the effects of high or low doses for patients with TMD. Follow-up analyses showed that LLLT significantly reduced pain at the short-term follow-up. Temporomandibular joint function outcomes indicated that the overall effect favored LLLT over placebo.ConclusionThis systematic review suggests that LLLT effectively relieves pain and improves functional outcomes in patients with TMD.
| S-EPMC5971344 | biostudies-literature
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| S-EPMC4822360 | biostudies-literature
Project description:PurposeBecause human bone marrow (BM) CD34+ stem cells home into damaged tissue and may play an important role in tissue repair, this pilot clinical trial explored the safety and feasibility of intravitreal autologous CD34+ BM cells as potential therapy for ischemic or degenerative retinal conditions.MethodsThis prospective study enrolled six subjects (six eyes) with irreversible vision loss from retinal vascular occlusion, hereditary or nonexudative age-related macular degeneration, or retinitis pigmentosa. CD34+ cells were isolated under Good Manufacturing Practice conditions from the mononuclear cellular fraction of the BM aspirate using a CliniMACs magnetic cell sorter. After intravitreal CD34+ cell injection, serial ophthalmic examinations, microperimetry/perimetry, fluorescein angiography, electroretinography (ERG), optical coherence tomography (OCT), and adaptive optics OCT were performed during the 6-month follow-up.ResultsA mean of 3.4 million (range, 1-7 million) CD34+ cells were isolated and injected per eye. The therapy was well tolerated with no intraocular inflammation or hyperproliferation. Best-corrected visual acuity and full-field ERG showed no worsening after 6 months. Clinical examination also showed no worsening during follow-up except among age-related macular degeneration subjects in whom mild progression of geographic atrophy was noted in both the study eye and contralateral eye at 6-month follow-up, concurrent with some possible decline on multifocal ERG and microperimetry. Cellular in vivo imaging using adaptive optics OCT showed changes suggestive of new cellular incorporation into the macula of the hereditary macular degeneration study eye.ConclusionsIntravitreal autologous BM CD34+ cell therapy appears feasible and well tolerated in eyes with ischemic or degenerative retinal conditions and merits further exploration. (ClinicalTrials.gov number, NCT01736059.).
| S-EPMC4288143 | biostudies-literature
Project description:Retinal degeneration is a debilitating ocular complication characterized by the progressive loss of photoreceptors and other retinal neurons, which are caused by a group of retinal diseases affecting various age groups, and increasingly prevalent in the elderly. Age-related macular degeneration, diabetic retinopathy and glaucoma are among the most common complex degenerative retinal disorders, posing significant public health problems worldwide largely due to the aging society and the lack of effective therapeutics. Whilst pathoetiologies vary, if left untreated, loss of retinal neurons can result in an acquired degeneration and ultimately severe visual impairment. Irrespective of underlined etiology, loss of neurons and supporting cells including retinal pigment epithelium, microvascular endothelium, and glia, converges as the common endpoint of retinal degeneration and therefore discovery or repurposing of therapies to protect retinal neurons directly or indirectly are under intensive investigation. This review overviews recent developments of potential neuroprotectants including neuropeptides, exosomes, mitochondrial-derived peptides, complement inhibitors, senolytics, autophagy enhancers and antioxidants either still experimentally or in clinical trials. Effective treatments that possess direct or indirect neuroprotective properties would significantly lift the burden of visual handicap.
| S-EPMC8848613 | biostudies-literature
Project description:PurposeThis review explores the role of pigment epithelium-derived factor (PEDF) in retinal degenerative and vascular disorders and assesses its potential both as an adjunct to established vascular endothelial growth factor inhibiting treatments for retinal vascular diseases and as a neuroprotective therapeutic agent.MethodsA comprehensive literature review was conducted, focusing on the neuroprotective and anti-angiogenic properties of PEDF. The review evaluated its effects on retinal health, its dysregulation in ocular disorders, and its therapeutic application in preclinical models. Advances in drug delivery, including gene therapy, were also examined.ResultsPEDF, initially identified for promoting neuronal differentiation, is also a potent endogenous angiogenesis inhibitor. Strong anti-angiogenic and neuroprotective effects are observed in preclinical studies. It has pro-apoptotic and antiproliferative effects on endothelial cells thereby reducing neovascularization. Although promising, clinical development is limited with only a single conducted phase I clinical trial for macular neovascularization. Development of PEDF-derived peptides enhances potency and specificity, and emerging gene therapy approaches offer sustained PEDF expression for long-term treatment. However, questions regarding dosage, durability, and efficacy remain, particularly in large animal models.ConclusionsPEDF shows significant therapeutic potential in preclinical models of retinal degeneration and vascular disorders. Despite inconclusive evidence on PEDF downregulation as a primary disease driver, many studies highlight its therapeutic benefits and favorable safety profile. Advances in gene therapy could enable long-acting PEDF-based treatments, but further research is needed to optimize dosage and durability, potentially leading to clinical trials and expanding treatment options for retinal disorders.
| S-EPMC11684118 | biostudies-literature
Project description:Background Disorders of consciousness (DoC) commonly occurs secondary to severe neurological injury. A considerable volume of research has explored the effectiveness of different non-invasive neuromodulation therapy (NINT) on awaking therapy, however, equivocal findings were reported. Objective The aim of this study was to systematically investigate the effectiveness on level of consciousness of different NINT in patients with DoC and explore optimal stimulation parameters and characteristics of patients. Methods PubMed, Embase, Web of Science, Scopus, and Cochrane central register of controlled trials were searched from their inception through November 2022. Randomized controlled trials, that investigated effectiveness on level of consciousness of NINT, were included. Mean difference (MD) with 95% confidence interval (CI) was evaluated as effect size. Risk of bias was assessed with revised Cochrane risk-of-bias tool. Results A total of 15 randomized controlled trials with 345 patients were included. Meta-analysis was performed on 13 out of 15 reviewed trials indicating that transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), and median nerve stimulation (MNS) all had a small but significant effect (MD 0.71 [95% CI 0.28, 1.13]; MD 1.51 [95% CI 0.87, 2.15]; MD 3.20 [95%CI: 1.45, 4.96]) on level of consciousness. Subgroup analyses revealed that patients with traumatic brain injury, higher initial level of consciousness (minimally conscious state), and shorter duration of prolonged DoC (subacute phase of DoC) reserved better awaking ability after tDCS. TMS also showed encouraging awaking effect when stimulation was applied on dorsolateral prefrontal cortex in patients with prolonged DoC. Conclusion tDCS and TMS appear to be effective interventions for improving level of consciousness of patients with prolonged DoC. Subgroup analyses identified the key parameters required to enhance the effects of tDCS and TMS on level of consciousness. Etiology of DoC, initial level of consciousness, and phase of DoC could act as significant characteristics of patients related to the effectiveness of tDCS. Stimulation site could act as significant stimulation parameter related to the effectiveness of TMS. There is insufficient evidence to support the use of MNS in clinical practice to improve level of consciousness in patients with coma. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337780, identifier: CRD42022337780.
| S-EPMC10246452 | biostudies-literature
Project description:BackgroundStem cell therapy is an emerging treatment for tendon disorders.PurposeTo systematically review the efficacy of stem cell therapy for patients with tendon disorders.Study designSystematic review; Level of evidence, 4.MethodsMEDLINE/PubMed, EMBASE, CINAHL, CENTRAL, PEDro, and SPORTDiscus; trial registers; and gray literature were searched to identify randomized controlled trials (RCTs) and non-RCTs, cohort studies, and case series with 5 or more cases. Studies investigating any type of stem cell therapy for patients with tendon disorders were eligible if they included patient-reported outcome measures or assessed tendon healing. Risk of bias was assessed through use of the Cochrane risk of bias tools.ResultsThis review included 8 trials (289 patients). All trials had moderate to high risk of bias (level 3 or 4 evidence). In Achilles tendon disorders, 1 trial found that allogenic-derived stem cells led to a faster recovery compared with platelet-rich plasma. Another study found no retears after bone marrow-derived stem cell therapy was used in addition to surgical treatment. There were 4 trials that studied the efficacy of bone marrow-derived stem cell therapy for rotator cuff tears. The controlled trials reported superior patient-reported outcomes and better tendon healing. A further 2 case series found that stem cell therapy improved patient-reported outcomes in patients with patellar tendinopathy and elbow tendinopathy.ConclusionLevel 3 evidence is available to support the efficacy of stem cell therapy for tendon disorders. The findings of available studies are at considerable risk of bias, and evidence-based recommendations for the use of stem cell therapy for tendon disorders in clinical practice cannot be made at this time. Stem cell injections should not be used in clinical practice given the lack of knowledge about potentially serious adverse effects.
| S-EPMC7227154 | biostudies-literature
Project description:IntroductionAllergic rhinitis (AR) is a common allergic disorder that impairs social and physical functioning as well as quality of life. It is characterized by sneezing, rhinorrhea, congestion, and itching which respond suboptimally to drug therapy. Low-level laser therapy (LLLT) has anti-inflammatory and immunosuppressive properties that have shown promise in some studies. We aimed to systematically review LLLT's effectiveness in treating AR and meta-analyze our findings.MethodsA systematic search of PubMed, Scopus, and Web of Science was conducted on November 24, 2023. All studies investigating LLLT on AR were included, and a pre-post meta-analysis of nasal symptoms (rhinorrhea, nasal congestion, nasal itching, and sneezing) in the LLLT-treated arm was conducted. Rhinoconjunctivitis quality of life questionnaire (RQLQ) scores before and after LLLT were also meta-analyzed alongside a pairwise meta-analysis of LLLT with placebo, acupuncture, steroids/antihistamines, and ultraviolet lasers. A random-effects model was used with a conservative pre-post correlation of 0.4 and standardized mean difference (SMD) as the effect size.ResultsSixteen studies were included in this review, and we found that nasal symptoms are alleviated post-LLLT in people with AR (SMD: -1.4, 95 CI: [-2.07 to -1.13], p value <0.001). RQLQ scores were also reduced after LLLT (SMD = -0.72, 95 CI: [-0.94 to -0.50], p value <0.001), and very few adverse events were reported. This meta-analysis, however, had significant publication bias and heterogeneity. When compared to a placebo, LLLT did not significantly improve nasal symptoms (SMD: -0.69, p value = 0.167), which might mean the post-LLLT nasal symptom alleviation is due to a placebo effect. Comparisons to other treatment modalities were too few to deduce anything meaningful, although it does appear that LLLT is less effective than UV lasers.ConclusionLLLT is most likely effective at alleviating nasal symptomology and has a low likelihood of adverse event incidence, yet more high-quality studies with larger sample sizes are needed to compare LLLT to a placebo to ensure its superiority to the placebo effect, as well as non-inferiority clinical trials to compare it to standard treatments.
| S-EPMC11370728 | biostudies-literature
Project description:PURPOSE OF REVIEW:The primary purpose of this review is to summarize current literature in the field of vestibular regeneration with a focus on recent developments in molecular and gene therapies. RECENT FINDINGS:Since the discovery of limited vestibular hair cell regeneration in mammals in the 1990s, many elegant studies have improved our knowledge of mechanisms of development and regeneration of the vestibular system. A better understanding of the developmental pathways of the vestibular organs has fueled various biological strategies to enhance regeneration, including novel techniques in deriving vestibular hair cells from embryonic and induced pluripotent stem cells. In addition, the identification of specific genetic mutations responsible for vestibular disorders has opened various opportunities for gene replacement therapy. SUMMARY:Vestibular dysfunction is a significant clinical problem with limited therapeutic options, warranting research on biological strategies to repair/regenerate the vestibular organs to restore function. The use of gene therapy appears promising in animal models of vestibular dysfunction.
| S-EPMC7173647 | biostudies-literature
Project description:IntroductionMigraine is a debilitating neurological disease with a multifaceted pathophysiology. Pre-existing comorbidities may influence the risk of developing migraine. This review and meta-analysis aim to present a comprehensive overview of the known comorbidities predisposing individuals to new migraine onset, thereby improving our understanding of the respective diseases' interactions.MethodsA systematic search of PubMed and EMBASE identified studies on pre-existing comorbidities as risk factors for new migraine onset. We performed three-level meta-analyses employing restricted maximum likelihood estimation to calculate pooled risk ratios (pRR). Subgroup and sensitivity analyses were conducted to assess the robustness of the data. Risk of bias (RoB) was assessed with the Quality in Prognostic Studies Tool. This review was pre-registered on Prospero (CRD42024501140).ResultsFrom a total of 17,330 records, we identified 38 studies, encompassing 124 effect sizes from 58 exposures. Most studies (n = 28, 74%) had a low RoB. Heterogeneity was high (>90%), primarily due to within-study differences (>50%), and was not significantly impacted by moderator tests or the exclusion of outliers. We found significantly increased risks for migraine onset associated with prior atopic conditions [pRR = 1.53 (1.15, 2.03)], psychiatric or psychological disorders [pRR = 2.63 (1.79, 3.85)], sleep disorders [pRR = 1.89 (1.26, 2.85)], and cardiovascular conditions [pRR = 1.72 (1.07, 2.76)].ConclusionsPre-existing atopic, psychiatric, sleep, and cardiovascular conditions are significantly associated with new migraine onset, likely due to shared genetic predisposition and mediating factors like stress and inflammation. Future research should focus on these associations to advance targeted prevention and treatment strategies.
| S-EPMC11880117 | biostudies-literature