Effects Of Stem Cell Therapy Research Articles

The Exosomes of Stem Cells from Human Exfoliated Deciduous Teeth Suppress Inflammation in Osteoarthritis.

Hyaluronic acid injection is commonly used clinically to slow down the development of osteoarthritis (OA). A newly developed therapeutic method is to implant chondrocytes/stem cells to regenerate cartilage in the body. The curative effect of stem cell therapy has been proven to come from the paracrine of stem cells. In this study, exosomes secreted by stem cells from human exfoliated deciduous teeth (SHED) and hyaluronic acid were used individually to evaluate the therapeutic effect in slowing down OA. SHED was cultured in a serum-free medium for three days, and the supernatant was collected and then centrifuged with a speed difference to obtain exosomes containing CD9 and CD63 markers, with an average particle size of 154.1 nm. SW1353 cells were stimulated with IL-1β to produce the inflammatory characteristics of OA and then treated with 40 μg/mL exosomes and hyaluronic acid individually. The results showed that the exosomes successfully inhibited the pro-inflammatory factors, including TNF-α, IL-6, iNOS, NO, COX-2 and PGE2, induced by IL-1β and the degrading enzyme of the extrachondral matrix (MMP-13). Collagen II and ACAN, the main components of the extrachondral matrix, were also increased by 1.76-fold and 2.98-fold, respectively, after treatment, which were similar to that of the normal joints. The effect can be attributed to the partial mediation of SHED exosomes to the NF-κB pathway, and the ability of exosomes to inhibit OA is found not inferior to that of hyaluronic acid.

ISL1-overexpressing BMSCs attenuate renal ischemia-reperfusion injury by suppressing apoptosis and oxidative stress through the paracrine action

Ischemia-reperfusion injury (IRI) is a major event in renal transplantation, leading to adverse outcomes. Bone marrow mesenchymal stem cells (BMSCs) are novel promising therapeutics for repairing kidney injuries. The therapeutic efficacy of BMSCs with ISL1 overexpression in renal IRI and its underlying mechanism need to be investigated. The unilateral renal IRI rat model was established to mimic clinical acute kidney injury. Rats were injected with PBS, BMSCs-Scrambled or BMSCs-ISL1 via the tail vein at the timepoint of reperfusion, and then sacrificed after 24 h of reperfusion. The administration of BMSCs-ISL1 significantly improved renal function, inhibited tubular cells apoptosis, inflammation, oxidative stress in rats. In vitro, HKC cells subjected to H2O2 stimulation were pretreated with the conditioned medium (CM) of BMSCs-Scrambled or BMSCs-ISL1. The pretreatment of ISL1-CM attenuated apoptosis and oxidative stress induced by H2O2 in HKC cells. Our proteomic data suggested that haptoglobin (Hp) was one of the secretory proteins in ISL1-CM. Subsequent experiments confirmed that Hp was the important paracrine factor from BMSCs-ISL1 that exerted anti-apoptotic and antioxidant functions. Mechanistically, Hp played a cytoprotective role via the inhibition of ERK signaling pathway, which could be abrogated by Ro 67-7476, the ERK phosphorylation agonist. The results suggested that paracrine action may be the main mechanism for BMSCs-ISL1 to exert protective effects. As an important anti-apoptotic and antioxidant factor in ISL1-CM, Hp may serve as a new therapeutic agent for treating IRI, providing new insights for overcoming the long-term adverse effects of stem cell therapy.

Effects of Stem Cell Therapy on Keloid Treatment: A Literature Review

Fibroblasts that produce excess collagen and growth factors play a role in the pathogenesis of keloid formation. In general, keloids are treated with intralesional corticosteroids alone or with a combination of other modalities, but the recurrence rate is still relatively high, so alternative treatments such as stem cells are being investigated, one of which is Mesenchymal Stem Cells (MSC), which have proven to be useful in healing keloids. Therefore, this literature review aims to discuss the effects of stem cell therapy in the treatment of keloids. In this literature review, 36 journals were used that discussed stem cell therapy in the treatment of keloids taken from various journal sources, namely Google Scholar, Pubmed, Medline, Ebsco, Hindawi, and Cochrane which were published within the last 10 years. According to the source, MSC is divided into 2 types, namely Adipose Mesenchymal Stem Cells (AMSC) and Bone Marrow Mesenchymal Stem Cells (BMMSC). In several studies, AMSC is known to reduce the expression of TGF-β1, COL-1, and COL-2 proteins, and has been shown to inhibit the proliferation of fibroblasts in keloid patients. Whereas in the BMMSC study that was applied with Hydroxybutyl chitosan (HBC) and Arg-Gly-Asp (RGD) hydrogels for 7 days, it was shown to significantly reduce nodular collagen fibers (p<0.05). Keloids occur due to excessive production of collagen and are influenced by various factors such as age, gender, skin color, and genetics. Stem cell therapy, such as MSC, has been proven in various studies to be an alternative treatment for keloids

Human Periodontal Ligament Stem Cells (hPDLSCs) Spontaneously Differentiate into Myofibroblasts to Repair Diabetic Wounds.

Advanced glycation end product (AGE) accumulation due to diabetes causes vascular and neurological lesions, delaying healing. The use of stem cells could overcome these problems. Although many studies have shown the potential beneficial effects of stem cell therapies in the treatment of chronic and refractory skin ulcers, their delivery methods are still under investigation. Human periodontal ligament stem cells (hPDLSCs) can spontaneously differentiate into myofibroblasts in specific cultures; therefore, they have the potential to effectively treat diabetic wounds and may also have applications in the field of medical cosmetics. The myofibroblastic differentiation ability of hPDLSCs in the presence of AGEs was evaluated by the expression of α-SMA and COL1A1 using RT-qPCR and WB technology. Wound healing in diabetic mice, induced by streptozotocin (STZ) and assessed using H&E staining, Masson staining, and immunohistochemical (IHC) and immunofluorescence (IF) staining, was used to validate the effects of hPDLSCs. In the wound tissues, the expression of α-SMA, COL1A1, CD31, CD206, iNOS, and vimentin was detected. The findings indicated that in H-DMEM, the expression of COL1A1 exhibited a significant decrease, while α-SMA demonstrated an increase in P7 cells, ignoring the damage from AGEs (p < 0.05). In an STZ-induced diabetic C57BL/6J mice whole-skin defect model, the healing rate of the hPDLSCs treatment group was significantly higher than that in the models (on the 7th day, the rate was 65.247% vs. 48.938%, p < 0.05). hPDLSCs have been shown to spontaneously differentiate into myofibroblasts in H-DMEM and resist damage from AGEs in both in vivo and in vitro models, suggesting their potential in the field of cosmetic dermatology.

Conditioned Media Therapy in Alzheimer's Disease: Current Findings and Future Challenges.

Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by a reduction in cognition and memory. Till now, there is no definite cure for AD, although, there are treatments available that may improve some symptoms. Currently, in regenerative medicine stem cells are widely used, mainly for treating neurodegenerative diseases. There are numerous forms of stem cells to treat AD aiming at the expansion of the treatment methods for this particular disease. Since 10 years ago, science has gained abundant knowledge to treat AD by understanding the sorts of stem cells, methods, and phasing of injection. Besides, due to the side effects of stem cell therapy like the potentiation for cancer, and as it is hard to follow the cells through the matrix of the brain, researchers have presented a new therapy for AD. They prefer to use conditioned media (CM) that are full of different growth factors, cytokines, chemokines, enzymes, etc. without tumorigenicity or immunogenicity such as stem cells. Another benefit of CM is that CM could be kept in the freezer, easily packaged, and transported, and doesn't need to fit with the donor. Due to the beneficial effects of CM, in this paper, we intend to evaluate the effects of various types of CM of stem cells on AD.

Recent advances in stem cells therapy: efficacy, ethics, safety concerns and future directions focusing on neurodegenerative disorders- a review

Neurodegeneration refers to the gradual loss of neurons and extensive changes occur in glial cells like tau inclusions in astrocytes and oligodendrocytes, α-synuclein inclusions in oligodendrocytes and SOD1 aggregates in astrocytes along with deterioration in the motor, cognition, learning, and behaviour. Common neurodegenerative disorders are Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease (HD), Spinocerebellar Ataxia (SCAs), and Supranuclear palsy are some common one. There is a lack of effective treatment for neurodegenerative diseases, and scientists are putting their efforts into developing therapies against them. Stem cell therapy has emerged as a hope for neurodegenerative disorders since it is not only the damaged neurons that might be replaced, but other neuromodulators and neuroprotectors are secreted. Stem cell terminal differentiation before implantation ensures the implantation of correct cells and molecular markers like carbonic anhydrase II, CNPase (2′,3′-cyclic nucleotide 3′-phosphohydrolase), myelin basic protein (MBP), and myelin oligodendrocyte glycoprotein ​(MOG) elucidate the differentiation. Secretion of various growth factors like epidermal growth factor (EGF), keratinocyte growth factor (KGF), vascular endothelial growth factor-α (VEGF-α), transforming growth factor (TGF) and macrophage inflammatory protein (MIP) supports cell survival, cell proliferation, blood vessel formation, axon regeneration, and neuroglial functional connection formation at the site of degeneration. Adverse effects of stem cell therapy, like teratogenicity and differentiation in different cells other than the desired one under the influence of microenvironment, are a few key concerns. Post-transplantation improved synaptic plasticity, apoptosis inhibition, and reduction in tau-phosphorylation and Amyloid beta (Aβ) production has been observed in Alzheimer’s patients.A large number of experimental, preclinical, and clinical studies have been conducted, and encouraging results have been obtained. The present review exhaustively discusses various kinds of stem cells, their usage in treating neurodegenerative disorders, limitations and challenges, and ethical issues related to stem cell therapy.

REVIVING HEARTS: A YOUTHFUL PERSPECTIVE ON STEM CELL THERAPY IN HEART FAILURE MANAGEMENT — A RCT META-ANALYSIS

Objective: Heart failure is a pervasive global health issue, and novel therapeutic approaches are continually explored to improve patient outcomes. Stem cell therapy has emerged as a promising avenue, offering regenerative potential for damaged cardiac tissue. This meta-analysis aims to comprehensively evaluate the impact of stem cell therapy on heart failure management from a youthful perspective. Design and method: A systematic literature search was conducted across major databases, identifying 20 randomized controlled trials (RCTs) published up to September 2021. These RCTs assessed stem cell interventions in heart failure patients. Data extraction and quality assessment were performed, with a specific focus on outcomes such as mortality rates, left ventricular ejection fraction (LVEF), and cardiac biomarkers. Effect sizes were calculated for these outcomes, and heterogeneity was assessed. Results: Our meta-analysis, comprising a robust dataset, highlights the substantial and statistically significant positive effect of stem cell therapy on key clinical outcomes. Specifically, stem cell therapy is associated with a significant reduction in all-cause mortality rates, underscoring its potential as a life-saving intervention. Furthermore, improvements in LVEF, a critical indicator of cardiac function, are notable and consistent across studies, reinforcing the therapeutic promise of stem cell treatments. Changes in cardiac biomarkers, such asB-type natriuretic peptide (BNP, also exhibit favourable trends with stem cell therapy, further supporting its efficacy. Conclusions: This meta-analysis, driven by a youthful perspective and supported by a substantial dataset, provides compelling and definitive evidence supporting the efficacy of stem cell therapy in improving heart failure outcomes. The findings of this study could have a powerful impact on clinical guidelines, advocating for the inclusion of stem cell therapy as a recommended approach in heart failure management. Future research should continue to explore the nuanced aspects of stem cell interventions to refine treatment strategies and unlock new possibilities in heart failure management.

Advances in stem cell therapy for articular cartilage lesions: clinical evidence and future directions: a systematic review

The significance of articular cartilage, an essential connective tissue, cannot be overstated in relation to joint health and functionality. Nevertheless, the human body might have adverse effects due to traumatic incidents, degenerative conditions, or repetitive stress, resulting in the manifestation of pain, inflammation, and impaired functionality. The primary objective of this study is to assess the effectiveness of stem cell therapy in the treatment of articular cartilage damage such as lesions. The systematic review was conducted adhering to the PRISMA principles. Boolean logic is employed in the search technique to integrate phrases pertaining to stem cell therapy, articular cartilage diseases, and biological processes. The research employs a range of databases and medical subject headings (MeSH) in order to facilitate a thorough examination. The stem cell therapy in the treatment of articular cartilage lesions has great potential. It enhances management and treatment outcomes for individuals afflicted with cartilage abnormalities. It is beneficial particularly those diagnosed with osteoarthritis (OA). Encouraging outcomes, such as alleviation of pain and improvement in functionality have been reported. Additional investigation is required to enhance therapy regimens, encompassing cell dosage, delivery techniques, and supplementary medicines. The use of stem cell therapies necessitates the imperative collaboration among researchers, doctors and regulatory agencies.

Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies.

Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.

Effectiveness of Stem Cell Therapy for Diabetic Foot Ulcers: A Systematic Review and GRADE Compliant Bootstrapped Meta-Analysis of Randomized Clinical Trials.

Diabetic foot (DF) represents a severe complication of diabetes mellitus, imposing substantial psychological and economic burdens on affected individuals. This investigation sought to assess the therapeutic efficacy of stem cell interventions in the management of DF complications. A comprehensive systematic search across PubMed, Embase, CINAHL, Scopus, and the Cochrane library databases was conducted to identify pertinent studies for meta-analysis. Outcome measures encompassed ulcer or wound healing rates, amputation rates, angiogenesis, ankle-brachial index (ABI), and pain-free walking distance. Dichotomous outcomes were expressed as risk differences (RDs) with 95% confidence intervals (CIs), while continuous data were articulated as standardized mean differences (SMDs) with corresponding 95% CIs. Statistical analyses were executed using RevMan 5.3 and Open Meta, with bootstrapped meta-analysis conducted through OpenMEE software. A total of 20 studies, comprising 24 arms and involving 1304 participants, were incorporated into the meta-analysis. The findings revealed that stem cell therapy exhibited superior efficacy compared to conventional interventions in terms of ulcer or wound healing rate [RD = 0.36 (0.28, 0.43)], pain-free walking distance [SMD = 1.27 (0.89, 1.65)], ABI [SMD = 0.61 (0.33, 0.88)], and new vessel development [RD = 0.48 (0.23, 0.78)], while concurrently reducing the amputation rate significantly [RD = -0.19 (-0.25, -0.12)]. Furthermore, no statistically significant difference in adverse events was observed [RD -0.07 (-0.16, 0.02)]. The Grading of Recommendations, Assessment, Development, and Evaluation assessment indicated varying levels of evidence certainty, ranging from very low to moderate, for different outcomes. Bootstrapping analysis substantiated the precision of the results. The meta-analysis underscores the significant superiority of stem cell therapy over conventional approaches in treating DF complications. Future investigations should prioritize large-scale, randomized, double-blind, placebo-controlled, multicenter trials, incorporating rigorous long-term follow-up protocols. These studies are essential for elucidating the optimal cell types and therapeutic parameters that contribute to the most effective treatment strategies for DF management.

The Miracle of Stem Cell Therapy for Post-Stroke Patients with Type 2 Diabetes

The objective of this research is to explain and analyze the miraculous effectiveness of stem cell therapy in treating post-stroke patients, particularly those with diabetes, and to study the consistent properties of this treatment method. The research method employed is a case study that administered stem cell therapy to five post-stroke patients with diabetes, aged between 53 and 72 years. Patient care records, including evaluations and analyses, serve as the primary data source for this study. The stem cells utilized in the therapy are derived from products cultured by the CELLTECH Stem Cell and Banking Laboratory, with processes undergoing thorough quality reviews. The study demonstrates that stem cells have proven to be capable of repairing damaged cells, especially in post-stroke therapy. Some patients undergoing therapy at the CELLTECH Stem Cell Center have successfully recovered and regained the ability to walk. These results are reinforced by a series of laboratory tests confirming their efficacy. Treatments conducted at the Vinski Regenerative Center also show positive research outcomes, enhancing confidence in the clinic's medical services. The implications of this research suggest that stem cell therapy could be an effective method in treating post-stroke patients with diabetes. The positive outcomes of this research could also bolster public trust in medical services provided by stem cell therapy centers such as CELLTECH Stem Cell Center and Vinski Regenerative Center. Further studies and the development of stem cell therapies may open new possibilities in the treatment of post-stroke and related conditions.

Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Effects of Stem Cell Therapy on Keloid Treatment: A Literature Review

Fibroblasts that produce excess collagen and growth factors play a role in the pathogenesis of keloid formation. In general, keloids are treated with intralesional corticosteroids alone or with a combination of other modalities, but the recurrence rate is still relatively high, so alternative treatments such as stem cells are being investigated, one of which is Mesenchymal Stem Cells (MSC), which have proven to be useful in healing keloids. Therefore, this literature review aims to discuss the effects of stem cell therapy in the treatment of keloids. In this literature review, 36 journals were used that discussed stem cell therapy in the treatment of keloids taken from various journal sources, namely Google Scholar, Pubmed, Medline, Ebsco, Hindawi, and Cochrane which were published within the last 10 years. According to the source, MSC is divided into 2 types, namely Adipose Mesenchymal Stem Cells (AMSC) and Bone Marrow Mesenchymal Stem Cells (BMMSC). In several studies, AMSC is known to reduce the expression of TGF-β1, COL-1, and COL-2 proteins, and has been shown to inhibit the proliferation of fibroblasts in keloid patients. Whereas in the BMMSC study that was applied with Hydroxybutyl chitosan (HBC) and Arg-Gly-Asp (RGD) hydrogels for 7 days, it was shown to significantly reduce nodular collagen fibers (p&lt;0.05). Keloids occur due to excessive production of collagen and are influenced by various factors such as age, gender, skin color, and genetics. Stem cell therapy, such as MSC, has been proven in various studies to be an alternative treatment for keloids

Efficacy of stem cell therapy for diabetic foot: Clinical evidence from meta-analyses.

To assess the clinical data on the effectiveness of stem cell therapy for diabetic foot (DF) based on recent systematic reviews and meta-analyses (SRs/MAs). SRs/MAs that evaluate the clinical evidence on the efficacy of stem cell therapy for DF were identified through a systematic search in public databases. The methodological quality and evidence quality of the included SRs/MAs were assessed separately by two researchers. Eight SRs/MAs were included in this analysis. Since there were no registered protocol or exclusion criteria for the included SRs/MAs, the methodological quality was rated as critically low. There was no high-quality evidence available for the outcomes, and the evidence quality ranged from critically low to moderate. Evidence degradation was most commonly caused by the risk of bias, followed by imprecision, publication bias and inconsistency. In conclusion, stem cell therapy may be effective for DF. However, this conclusion should be approached with caution, considering the quality of the supporting SRs/MAs.

Stem Cell Therapy for Liver Diseases: Current Perspectives.

Stem cell therapy offers a promising avenue for advanced liver disease cases as an alternative to liver transplantation. Clinical studies are underway to explore the potential of stem cells from various sources in treating different liver diseases. However, due to the variability among current studies, further validation is needed to ensure the safety and effectiveness of stem cell therapy. To establish a strong foundation for optimal stem cell therapy applications, selection of suitable stem cell sources, standardization of transplantation protocols, and patient criteria are vital. This review comprehensively examines existing literature on stem cell sources, transplantation methods, and patient selection. Additionally, we discuss novel strategies, including stem cell preconditioning, cell-free therapy, genetic modification of stem cells, and the use of liver organoids, addressing the limitations of current stem cell therapies. Nevertheless, these innovative approaches require further validation.

Stem Cell Therapy for Diabetic Foot: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Objective: This umbrella review aims to summarize and evaluate the evidence from current systematic reviews/meta-analyses (SRs/MAs) on the effectiveness of stem cell therapy for diabetic foot (DF). Approach: We conducted a comprehensive search in four databases for SRs/MAs that included randomized controlled trials (RCTs) on stem cell therapy for DF. Two separate researchers independently evaluated the methodological quality and evidence quality of the SRs/MAs that were included in the study. We conducted a quantitative synthesis of all RCTs included in the SRs/MAs to obtain objective and updated conclusions. Egger's test and sensitivity analysis are used to examine the reliability of the results. Results: This umbrella review includes eight SRs/MAs, and their methodological quality and evidence quality were all deemed unsatisfactory. Out of the 8 SRs/MAs, 26 RCTs were included, with a total corrected covered area of 21.4%, indicating a high degree of overlap. The test of super-significance did not yield any significant results. Our updated meta-analysis suggests that DF patients can benefit from stem cell therapy, as indicated by effectiveness in measures, including healing rate, amputation rate, ankle-brachial index, transcutaneous oxygen pressure, ulcer size reduction, complete healing time, pain-free walking distance, rest pain score, and new angiogenesis rate. Innovation: This study conducted a comprehensive evaluation and reanalysis of the current evidence regarding the effectiveness and safety of stem cell therapy for DF, which is the first of its kind. Conclusion: Based on the existing evidence, stem cell therapy is effective and safe for patients with DF.

Potential Plausible Role of Stem Cell for Treating Depressive Disorder: a Retrospective Review.

Depression poses a significant threat to global physical and mental health, impacting around 3.8% of the population with a rising incidence. Current treatment options primarily involve medication and psychological support, yet their effectiveness remains limited, contributing to high relapse rates. There is an urgent need for innovative and more efficacious treatment modalities. Stem cell therapy, a promising avenue in regenerative medicine for a spectrum of neurodegenerative conditions, has recently garnered attention for its potential application in depression. While much of this work remains preclinical, it has demonstrated considerable promise. Identified mechanisms underlying the antidepressant effects of stem cell therapy encompass the stimulation of neurotrophic factors, immune function modulation, and augmented monoamine levels. Nonetheless, these pathways and other undiscovered mechanisms necessitate further investigation. Depression fundamentally manifests as a neurodegenerative disorder. Given stem cell therapy's success in addressing a range of neurodegenerative pathologies, it opens the door to explore its application in depression treatment. This exploration may include repairing damaged nerves directly or indirectly and inhibiting neurotoxicity. Nevertheless, significant challenges must be overcome before stem cell therapies can be applied clinically. Successful resolution of these issues will ultimately determine the feasibility of incorporating stem cell therapies into the clinical landscape. This narrative review provides insights into the progress of research, potential avenues for exploration, and the prevailing challenges in the implementation of stem cell therapy for treatment of depression.

The Safety and Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Patients With Heart Failure and Myocardial Infarction: A Meta-Analysis of Clinical Trials.

Evidence from preclinical and clinical studies suggests that human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) may be useful in treating heart failure and acute myocardial infarction (MI). However, the effects of stem cell therapy on patients with heart failure remain the subject of ongoing controversy, and the safety and effectiveness of HUC-MSCs therapy have not yet been proven. To date, there has been no systematic overview and meta-analysis of clinical studies using HUC-MSCs therapy for heart failure and MI. The purpose of this study is to assess the safety and efficacy of HUC-MSC therapy versus a placebo in patients with heart failure and MI. While preparing this systematic review and meta-analysis, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer literature search of PubMed was performed. We considered randomized controlled trials (RCTs) that reported data on the safety and efficacy of HUC-MSC transplantation in patients with heart failure and MI. Two investigators independently searched the literature, extracted data, and rated the quality of the included research. Pooled data were analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was ejection fraction (EF), whereas the secondary outcomes were readmission and mortality rates. Three RCTs (201 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of risk of readmission (risk ratio = 0.5, 95% confidence interval (CI) = 0.22-1.15, p = 0.10) as well as mortality rate (risk ratio = 0.44, 95% CI = 0.14-1.44, p = 0.18). However, there was an improvement in EF in patients who received HUC-MSCs compared to placebo after 12 months of transplantation (mean difference (MD) = 3.21, 95% CI = 2.91-3.51, p < 0.00001). At the six-month follow-up period, there was no significant improvement in EF (MD = 1.30, 95% CI = -1.94-4.54), p = 0.43), indicating that the duration of follow-up can shape the response to therapy. Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates. Existing evidence is insufficient to confirm the efficacy of HUC-MSCs for broader therapeutic applications. Therefore, additional double-blind RCTs with larger sample sizes are required.

TNF-α and IFN-γ prestimulation enhances the therapeutic efficacy of human amniotic epithelial stem cells in chemotherapy-induced ovarian dysfunction

BackgroundExposure to a harsh ovarian microenvironment induced by chemotherapeutic agents seriously affects the remodeling of ovarian function and follicular development, leading to premature ovarian failure or insufficiency (POF/POI). For decades, the effectiveness of stem cell therapies in POI animal models has been intensively studied; however, strategies to enhance the therapeutic effect of stem cells remain challenging.MethodsIn this study, we first observed the pathological changes of the ovaries at different time points during chemotherapy, including the number of follicles, granulosa cell proliferation, oxidative stress damage, ovarian fibrosis, and inflammatory reaction. Moreover, we investigated whether activated hAECs stimulated by the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were more effective than native hAECs in repairing ovarian injury induced by chemotherapy.ResultsThe inhibitory effect of chemotherapy drugs on ovarian granulosa cells (GCs) in growing follicles mainly occurred on day 3 after chemotherapy in a mouse model. Then, continued ovarian injury, including oxidative damage and cell death cascades, resulted in the depletion of follicular reserves and inflammation-related ovarian fibrosis. Cytokine array demonstrated that activated hAECs secreted high levels of paracrine cytokines related to extracellular matrix (ECM) remodeling, angiogenesis, and immunomodulation. An in vivo study showed that the engraftment rate of activated hAECs in damaged ovaries was higher than that of native hAECs. Furthermore, activated hAECs in damaged ovaries had significantly upregulated expression of the antioxidant proteins thioredoxin1/2. In addition, activated hAECs had increased numbers of mature follicles and ameliorated the ovarian microenvironment by promoting angiogenesis and reducing ovarian fibrosis.ConclusionsThese results indicated that secondary ovarian damage induced by chemotherapy, including oxidative stress damage, chronic inflammatory response, and ovarian tissue fibrosis should be attended. Prestimulation with the proinflammatory factors TNF-α and IFN-γ could enhance the therapeutic efficacy of hAECs against chemotherapy-induced ovarian dysfunction, which may become a new feasible strategy to improve the therapeutic potential of hAECs in regenerative medicine.Graphical

Theoretical study of diffusive model of HIV-1 infection and its analytical solution.

T his article studied a mathematical model for the diffusive human immunodeficiency virus-type 1 (HIV-1) infection combining with stem cell therapy. The HIV-1 infection is a chronic disease and the viral replication continues if the patient stopes use the antiretroviral therapy (cART). Therefore, it is important to seek the cure of HIV-1 infection and some medical trials showed the cure by stem cell therapy and there are others failure to achieve the cure of HIV-1 with same treatments. The novelty of this paper is constructing a mathematical model with adding diffusion terms to study the effect of spread of virus and other cells in the body. Theoretical analysis such as boundedness, positivity, stability (local/global) of the HIV-1 model is presented. The model is solved analytically by the tanh expansion method. The results show that the tanh expansion method is a very useful technique, that can give a good prediction of the effect of stem cell therapy on infected cells on the spread of the virus. The results further demonstrated that the best way to control the disease is by limiting the spread of the virus; more so than the spread of other components.