Effects Of Stem Cell Therapy Research Articles

Unlocking the Potential of Mesenchymal Stem Cells in Gynecology: Where Are We Now?

Stem cells, with their remarkable capacity for differentiation into diverse cell types, are vital for the development as well as maintenance of health and homeostasis. Two unique abilities set them apart from other cells: self-renewal and the capacity for differentiation. They play important roles in embryogenesis, development, regeneration, and various other processes. Over the last decade, there has been increased interest in their potential use in the treatment of numerous diseases and disorders across multiple fields of medicine in acute, chronic, innate, and acquired diseases. Stem cells are key to maintaining the body's homeostasis and regulating growth and tissue functions. There are several types of stem cells-embryonic, adult, and human-induced pluripotent cells. Currently, mesenchymal stem cells are of great interest due to their regenerative, immunomodulatory, analgesic, and antimicrobial (anti-inflammatory) effects. Recent studies have shown the potent regenerative effect of stem cell therapy in gynecologic diseases such as infertility, Asherman syndrome, lichen sclerosus, polycystic ovary syndrome, premature ovarian insufficiency, genitourinary syndrome of menopause, and rectovaginal fistulas. Moreover, the successful isolation of oogonial stem cells could lead to a revolution in the field of gynecology and the potential treatment of the conditions discussed. This review aims to provide a better understanding of the latest therapeutic options involving stem cells and raise awareness of this promising yet not widely known topic in gynecology and medicine in general.

Stem cells for neonatal brain injury – Lessons from the bench

Neonatal brain injury resulting from various intractable disorders including intraventricular hemorrhage and hypoxic ischemic encephalopathy still remains a major cause of mortality and morbidities with few effective treatments. Recent preclinical research results showing the pleiotropic neuroprotective effects of stem cell therapy, specifically mesenchymal stem cells (MSCs), suggest that MSCs transplantation might be a promising new therapeutic modality for neuroprotection against the currently intractable and devastating neonatal brain injury with complex multifactorial etiology. This review summarizes recent advances in preclinical stem cell research for treating neonatal brain injury with a focus on the important issues including the mechanism of neuroprotection, and determining the ideal cell source, route, timing and dose of MSCs transplantation.

Efficacy and Potential of Stem Cell Therapy for Alzheimer’s Disease

Alzheimer’s Disease (AD) is characterized primarily by the buildup of beta-amyloid plaques and tau proteins. It is a very common neurodegenerative disease that is marked by cognitive decline, neuronal and synaptic loss. AD pathology is not fully understood and there is currently no cure. The disease is terminal and devastates the lives of many. Stem cell therapy involves the use of stem cell’s properties of regeneration and repair to reverse the damage of many diseases. The application of stem cell therapy to AD seems to have the promise to mitigate and reverse the onset of AD. Animal models have displayed the effectiveness of stem cell therapy towards AD by improving cognitive performance and promoting neurogenesis. The abilities and applications of stem cell therapy seem to be highly promising despite having bottlenecks. The difficulties in controlling differentiation due to complexities in controlling the process is the primary issue presented. With the use of stem cell therapy for AD, it is also possible to adapt the technology to various other neurodegenerative diseases and various diseases overall.

Impact of adipose-derived stem cells on aortic tensile strength in a model of abdominal aortic aneurysm

IntroductionAbdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment. Methods16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm piece of Gelfoam, an absorbable gelatin-based hemostatic agent, was soaked in media or human MSCs and placed directly on the vessel for control and experimental animals. At postoperative day 21, animals were sacrificed and the infrarenal aorta at this location was harvested for analysis. Tensile strength was measured using a tensiometer, from which Young's modulus and maximum strain were calculated. ResultsAll animals survived the surgery and post-operative course. Young's elastic modulus for the aneurysm control group was 15.83 ± 1.61 compared to 22.13 ± 2.34 for the stem cell treated segment, p = 0.0316. There was no significant difference in the peak stress between groups. ConclusionsThis is the first study to demonstrate the mechanical effects of stem cell therapy on a model of AAA in swine. Young's modulus, which characterizes the intrinsic capacity of a tissue to withstand stress, was greater in the animals treated with MSCs compared to control animals with aneurysms. This methodology can be utilized in future large animal models to develop cell and drug-based therapies for AAA.

Theoretical study and numerical simulation for a mathematical model of diffusive cancer with effect of stem cell therapy and chemotherapy

Cancer is the most dangerous disease in the world. Therefore, this paper is devoted to studying a mathematical model of diffusive cancer and the effect of its treatments. One of the cancer treatments currently being explored is stem cell transplant, which works to stimulate and strengthen the immune system while the patient receives chemotherapy. This work introduces a mathematical system for the temporal and spatial interactions between the tumor, stem cells and effector cells during chemotherapy and the extent of the spread of these interactions within the tissue. Also, we study the stability of the system through the equilibrium points of the reaction-diffusion model. In addition, the existence, uniqueness, positivity, and boundedness are proven. We found a numerical simulation by the finite difference method and observed a dynamic of the solutions. Also, we described the tumor behaviour before and after the treatments and the effect of its diffusion.

Mitochondria in Cell-Based Therapy for Stroke.

Despite a relatively developed understanding of the pathophysiology underlying primary and secondary mechanisms of cell death after ischemic injury, there are few established treatments to improve stroke prognoses. A major contributor to secondary cell death is mitochondrial dysfunction. Recent advancements in cell-based therapies suggest that stem cells may be revolutionary for treating stroke, and the reestablishment of mitochondrial integrity may underlie these therapeutic benefits. In fact, functioning mitochondria are imperative for reducing oxidative damage and neuroinflammation following stroke and reperfusion injury. In this review, we will discuss the role of mitochondria in establishing the anti-oxidative effects of stem cell therapies for stroke.

Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.

Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD. hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments. The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain. hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

Mechanism of Thymus Rejuvenation in Elderly Macaques.

Senile thymus atrophy is an important factor leading to decreased immune function. Repairing the atrophic thymus tissue structure, rebuilding immune function, and replenishing the number of exogenous stem cells may be ideal methods. In this study, bone marrow mesenchymal stem cells were intravenously infused into elderly macaques. We found that thymus volume was substantially increased, some thymus tissue regeneration was observed, the degree of thymus tissue fibrosis decreased, collagen fiber deposition decreased, cortical and medulla structures emerged gradually, the number of apoptotic cells decreased significantly, and the expression of apoptosis-related proteins decreased. For the effects of stem cell therapy on aging-related genes, we performed transcriptomic analysis of thymus tissue. The results show the expression pattern of the tissue transcriptome tended to be similar to the thymus expression pattern in young macaques compared with the elderly group, reverse aging-related proteins. Based on the results, it is suggested that stem cell therapy is an ideal method to prevent or reverse the aging of the thymus.

Efficacy of stem cell therapy in animal models of intracerebral hemorrhage: an updated meta-analysis

BackgroundMultiple studies have reported that stem cell therapy has beneficial effects in animal models of intracerebral hemorrhage (ICH). However, this finding remains inconclusive. This study was performed to systematically determine the effect size of stem cell therapy in ICH animal models by pooling and analyzing data from newly published studies.MethodsA literature search identified studies of stem cells in animal models of ICH. We searched mainstream databases from inception to November, 2021. And pooled effect size of stem cells was determined for diversified neurobehavioral scales and structural endpoints using random effects models.ResultsThe median quality score of 62 included studies was 5.32. Our results revealed an overall positive effect of stem cell therapy. More specifically, the SMD was − 2.27 for mNSS, − 2.14 for rotarod test, − 2.06 for MLPT, − 1.33 for cylinder test, − 1.95 for corner turn test, − 1.42 for tissue loss, and − 1.86 for brain water content. For mNSS, classifying comparisons by quality score showed significant differences in estimates of effect size (p = 0.013), and high-quality comparisons showed a better outcome (SMD = − 2.57) compared with low-quality comparisons (SMD = − 1.59). Besides, different delivery routes also showed a significant difference in the estimates of effect size for mNSS (p = 0.002), and the intraperitoneal route showed the best outcome (SMD = − 4.63). For tissue loss, the autologous blood-induced ICH model showed a better outcome (SMD = − 1.84) compared with the collagenase-induced ICH model (SMD = − 0.94, p = 0.035). Additionally, stem cell therapy initiated within 8 h post-ICH showed the greatest efficacy on tissue loss reduction, followed by initiated with 24 h post-ICH. Finally, stem cells with different sources and types showed similar beneficial effects for mNSS as well as tissue loss.ConclusionsOur results suggested that stem cell therapy had remarkable benefits on ICH animals on both the functional and structural outcomes in animal models of ICH, with very large effect size. These findings support the utility of further studies to translate stem cells in the treatment of ICH in humans. Moreover, the results should be interpreted in the light of the limitations in experimental design and the methodological quality of the studies included in the meta-analysis.

Clinical outcome and safety of stem cell therapy for ischemic stroke: A systematic review and meta-analysis.

Background: Several reports on stem cell administration have emerged proving it to be an ideal therapeutic approach for improving neurological functions in ischemic stroke patients. However, some studies also show disappointing results, with some reporting no statistically significant improvements among several different parameters. Several challenges also arise relating to safety and nonscientific aspects, such as ethics.Methods: We performed a systematic review and meta-analysis to evaluate the effect of stem cell therapy on the clinical outcomes of ischemic stroke patients. A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A thorough literature search was conducted on PubMed, Scopus, and Cochrane databases. Articles were selected systematically based on the PRISMA protocol and reviewed completely. A total of 19 publications pertaining to stem cell therapy on the ischemic route were included and reviewed. Efficacy outcomes were measured with the National Institutes of Health Stroke Scale, modified Rankin Scale, or Barthel Index.Results: The results of the meta-analysis indicate that the efficacy outcomes suggest favorable results after stem cell therapy, although not all study results are statistically significant. Stem cell therapy in stroke cases showed a better outcome than standard conservative therapy alone, although our analysis shows that many factors can influence this outcome, and significant effects can only be seen after several months.Conclusion: The results of this study show promising and satisfying efficacy and a relatively low rate of serious adverse events.

Potential application of biomimetic exosomes in cardiovascular disease: focused on ischemic heart disease

Cardiovascular disease, especially ischemic heart disease, is a major cause of mortality worldwide. Cardiac repair is one of the most promising strategies to address advanced cardiovascular diseases. Despite moderate improvement in heart function via stem cell therapy, there is no evidence of significant improvement in mortality and morbidity beyond standard therapy. The most salutary effect of stem cell therapy are attributed to the paracrine effects and the stem cell-derived exosomes are known as a major contributor. Hence, exosomes are emerging as a promising therapeutic agent and potent biomarkers of cardiovascular disease. Furthermore, they play a role as cellular cargo and facilitate intercellular communication. However, the clinical use of exosomes is hindered by the absence of a standard operating procedures for exosome isolation and characterization, problems related to yield, and heterogeneity. In addition, the successful clinical application of exosomes requires strategies to optimize cargo, improve targeted delivery, and reduce the elimination of exosomes. In this review, we discuss the basic concept of exosomes and stem cell-derived exosomes in cardiovascular disease, and introduce current efforts to overcome the limitations and maximize the benefit of exosomes including engineered biomimetic exosomes.

Foraging for the Optimal Dressing Scaffold to Carry Adipose-Derived Stromal/Progenitor Cells for Cell Therapy

In our daily plastic surgery practice, we have seen many chronic wounds that need new biotechnology to help and improve wound healing. Stem cells play a crucial role in regenerative medicine. Many pre-clinical researches had reported the beneficial paracrine effects of stem cell therapy for chronic wounds. Cell-friendly scaffolds may provide the protection and three-dimensional space required for adherence of stem cells, thus allowing these stem cells to proliferate and differentiate for treatment purpose. A successful scaffold may enhance the effects of stem cell therapy. In this presented series, the authors attempted to identify the most suitable scaffolds from several commercially available wound dressings that could sustain adipose-derived stromal/progenitor cells (ADSCs) survival. Therefore, we isolated ADSCs containing the green fluorescent protein (GFP) from GFP transgenic rats. The GFP (+) ADSCs and their progenies could be easily observed using a fluorescence microscope. Moreover, we analyzed the cytokines secreted in condition medium (CM) to understand the activities of ADSCs in various dressings. Our results showed that the foam dressings, hydrofiber, chitosan, and alginate plus carboxymethylcellulose were identified as the most suitable dressing materials. Higher concentrations of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) were observed 48 h after loading them with GFP (+) ADSCs. Therefore, multiple topical cell therapy using ADSCs can be performed by applying suitable dressing scaffolds without repeated needle injections to deliver the stem cells into the wound bed. Based on their fluorescence property, the GFP (+) ADSCs can also possibly be used for testing biocompatibility of medical materials in the future.

Efficacy and Safety of Stem Cell Therapy in Diabetic Retinopathy: A Scoping Review

Background: Diabetic Retinopathy (DR) is a microvascular disorder that arises due to chronic hyperglycemia, which, if left untreated, would ultimately cause loss of vision. Although there are some established treatments for DR, those treatments failed to show a capability to induce cellular regeneration. Stem cells are unspecialized cells of the human body that would be able to differentiate and have the ability to self-regeneration and recently emerged as a potential treatment for DR. Aim: The aim of this review is to evaluate the ability of stem cells as a treatment for DR by promoting cellular regeneration and evaluate the safety of stem cell treatment. Method: We identified relevant articles from three established databases and did an advanced search using a combination of Medical SubHeading Terms (MeSH Terms) keywords and boolean operators such as: (“Diabetic Retinopathy” [MeSH Terms]) AND stem cells [MeSH Terms]”. Result: In this scoping review, the authors identified thirteen studies that meet the inclusion criteria. Of the twelve pre-clinical studies, eleven studies evaluated cellular regeneration, and five studies evaluated neurotrophic factors. Only two studies reported side effects of stem cell therapy in pre-clinical studies. Only one clinical study was identified that evaluated the cellular regeneration of stem cell therapy in DR. Conclusion: Several types of stem cells have been researched as a new therapeutic modality for Diabetic Retinopathy. Most studies showed successful application as noted on its ability to promote and preserve cell regeneration as well as increase neurotrophic factors of the retina with no serious adverse effects are reported.

The role of hypoxia in stem cell regulation of the central nervous system: From embryonic development to adult proliferation.

Hypoxia is involved in the regulation of various cell functions in the body, including the regulation of stem cells. The hypoxic microenvironment is indispensable from embryonic development to the regeneration and repair of adult cells. In addition to embryonic stem cells, which need to maintain their self‐renewal properties and pluripotency in a hypoxic environment, adult stem cells, including neural stem cells (NSCs), also exist in a hypoxic microenvironment. The subventricular zone (SVZ) and hippocampal dentate gyrus (DG) are the main sites of adult neurogenesis in the brain. Hypoxia can promote the proliferation, migration, and maturation of NSCs in these regions. Also, because most neurons in the brain are non‐regenerative, stem cell transplantation is considered as a promising strategy for treating central nervous system (CNS) diseases. Hypoxic treatment also increases the effectiveness of stem cell therapy. In this review, we firstly describe the role of hypoxia in different stem cells, such as embryonic stem cells, NSCs, and induced pluripotent stem cells, and discuss the role of hypoxia‐treated stem cells in CNS diseases treatment. Furthermore, we highlight the role and mechanisms of hypoxia in regulating adult neurogenesis in the SVZ and DG and adult proliferation of other cells in the CNS.

Effectiveness of Stem Cell Therapy in Autism Spectrum Disorders: Case Study of Identical Twins

Autism Spectrum Disorders (ASDs) is a neurodevelopmental disorder with immune system dysfunction. Recent year’s researches have exposed importance of cell based therapies, which were proposed and applied to ASDs as ASDs are considered to be a Neurobiological condition. Although a few studies show stem cell therapy as an active treatment, method for individuals with ASDs there is a lack of empirical evidences to confirm the effectiveness. A twin case study is presented who are diagnosed as having ASDs who had undergone Stem cell therapy treatment. The results of detailed Speech and Language evaluations and other treatments the children had undergone are the focus of present report. Precautions to be taken while choosing the right management option, which involves careful parental counselling are discussed.

Effectiveness of Stem Cell Therapies in Improving Clinical Outcomes in Patients With Heart Failure.

Heart failure (HF), continuing to be a notable cause of morbidity and mortality worldwide, also is a noteworthy economic burden to the patients. Current medical management of HF has poor efficacy to completely arrest or reverse the progression to end-stage disease. As the option of cardiac transplantation remains limited to few patients, the stem cell approach continues to be a promising one in developing a novel therapy in the treatment of HF.This review attempts to discuss and compare the outcomes of numerous clinical trials that involved treatment of HF of variable etiologies with stem cells of numerous lineages such as bone marrow-derived cells (BMCs), mesenchymal stem cells (MSCs), cardiosphere derived progenitor cells (CDCs), etc. We reviewed articles and randomized controlled trials (RCT) that used stem cells to treat heart failure. The articles and RCT studies were obtained through a search on PubMed and Medline databases and performed using regular and medical subject heading (MeSH) keyword search strategy. A total of 17 trial-based studies, along with other articles that met the aim of the review, were selected. A discussion of the findings from major clinical trials such as the C-CURE, CHART-1, POSEIDON, POSEIDON-DCM, TAC-HFT, and other small scale trials highlights the change in functional and mechanical parameters of HF, namely, left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), end-systolic volume (ESV), 6-minute walking test distance (6MWTD), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and assessment of New York heart association (NYHA) class of heart failure, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score to reflect improvement in quality of life (QoL) of patients.Out of the studies analyzed, the majority reported significant improvements in at least two of the parameters mentioned above. However, more phase three randomized trials are required to compare the efficacy of multiple lineages of stem cells, factoring in molecular and dosage factors to develop a standardized therapy.

Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review.

ABSTRACTStem cell therapy has been used to treat several types of diseases, and it is expected that its therapeutic uses shall increase as novel lines of evidence begin to appear. Furthermore, stem cells have the potential to make new tissues and organs. Thus, some scientists propose that organ transplantation will significantly rely on stem cell technology and organogenesis in the future. Stem cells and its robust potential to differentiate into specific types of cells and regenerate tissues and body organs, have been investigated by numerous clinician scientists and researchers for their therapeutic effects. Degenerative diseases in different organs have been the main target of stem cell therapy. Neurodegenerative diseases such as Alzheimer’s, musculoskeletal diseases such as osteoarthritis, congenital cardiovascular diseases, and blood cell diseases such as leukemia are among the health conditions that have benefited from stem cell therapy advancements. One of the most challenging parts of the process of incorporating stem cells into clinical practice is controlling their division and differentiation potentials. Sometimes, their potential for uncontrolled growth will make these cells tumorigenic. Another caveat in this process is the ability to control the differentiation process. While stem cells can easily differentiate into a wide variety of cells, a paracrine effect controlled activity, being in an appropriate medium will cause abnormal differentiation leading to treatment failure. In this review, we aim to provide an overview of the therapeutic effects of stem cells in diseases of various organ systems. In order to advance this new treatment to its full potential, researchers should focus on establishing methods to control the differentiation process, while policymakers should take an active role in providing adequate facilities and equipment for these projects. Large population clinical trials are a necessary tool that will help build trust in this method. Moreover, improving social awareness about the advantages and adverse effects of stem cell therapy is required to develop a rational demand in the society, and consequently, healthcare systems should consider established stem cell-based therapeutic methods in their treatment algorithms.

Highly interconnected inverse opal extracellular matrix scaffolds enhance stem cell therapy in limb ischemia

The therapeutic effectiveness of cell transplantation in treatment of diseases and injuries is often limited by low cell retention, survivability, and engraftment. Extracellular matrix (ECM)-derived scaffolds are capable of controlling cell responses, thereby offering potential solutions to current challenges associated with cell therapy. However, it remains a technical challenge to produce ECM scaffolds with highly interconnected porous structure specifically required for cell transplantation. Here, we developed inverse opal porous extracellular matrix (ioECM) scaffolds through subcutaneous implantation of sacrificial templates assembled from polymer microspheres, followed by removal of the microsphere template and cellular content. Such highly interconnected porous ioECM scaffolds supported the anchorage, survival, viability, anti-apoptotic and paracrine activities of rat bone marrow mesenchymal stem cells (BMSCs), which further promoted endothelial cell migration and tube formation and viability. Upon transplantation into nude mouse critical limb ischemic model, ioECM promoted the engraftment of laden BMSCs, facilitated interconnected vascular network formation with accelerated recovery of blood perfusion and inhibited muscle atrophy and fibrosis. Our study demonstrates a unique strategy to engineer highly porous yet well-interconnected ECM scaffolds specifically for cell transplantation with marked improvement of survivability and vascularization, which offers an essential step toward the success of cell therapy and regenerative medicine. Statement of significanceCell-based therapy has a good developing foreground applied in a variety of tissue regeneration. Extracellular matrix (ECM) scaffolds is an optimal choice for cell delivery duo to its superior biocompatibility and favorable immune responses. However, the current ECM scaffolds lacking of the controllable pore structure restrict the cell delivery efficiency and therapeutic outcome. Here, we fabricated highly interconnected inverse opal extracellular matrix (ioECM) scaffolds, which can enhance the effect of stem cell therapy in limb ischemic model by improving the survival, viability, and paracrine activities of stem cells. Our study provides reference value for the design and fabrication of ECM based biomaterials for cell transplantation.

Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence.

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro (p < 0.01), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

Combined Effects of Low Level Laser Therapy and Inducers on the Neural Differentiation of Mesenchymal Stem Cells

Low level laser therapy (LLLT) improves the therapeutic effectiveness of stem cell therapy for neurological injury through its ability to enhance stem differentiation and protect against neuronal apoptosis through its antioxidation effects. However, the specific mechanisms governing these effects are poorly defined. In this study, we investigated the effects of LLLT on stem cell differentiation at the molecular level, oxidative stress balance, and inflammatory factors to provide theoretical support for its clinical application. Cell viability was assessed via MTT assays. Reactive oxygen species (ROS), total superoxide dismutase (SOD), and total antioxidant capacity (TAC) were used to evaluate oxidative stress levels. Western blot analysis was used to quantitatively investigate protein expression. The levels of secreted proteins and tumor necrosis factor- $\alpha $ (TNF- $\alpha$ ) and interleukin- $1\beta $ (IL- $1\beta$ ) expression were measured by ELISA. Compared to LLLT at 808 nm, LLLT at 635 nm enhanced the proliferation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs). The rates of proliferation markedly increased at a power density 20 mW/cm2. LLLT enhanced the antioxidant capacity and caused no inflammation in normal cells. Markers of neural precursors were more highly expressed at 808 nm when combined with inducers for 3 d, compared to the more modest increases observed at 635 nm. The expression of neuN on day 7 also increased, most notably when LLLT at 808 nm was combined with cerebrospinal fluid (CSF)/injured cerebrospinal fluid (iCSF). ELISA assays showed that LLLT at 808 nm with CSF/iCSF also increased the differentiation of hUCMSCs into neurons. LLLT at 808 nm combined with inducers promoted the differentiation into neurons and increased the rate of neuronal differentiation.