Therapeutic Effects Of Stem Cells Research Articles

Human amnion mesenchymal stem cells promote endometrial repair via paracrine, preferentially than transdifferentiation

BackgroundIntrauterine adhesion (IUA) is one of the most severe causes of infertility in women of childbearing age with injured endometrium secondary to uterine performance. Stem cell therapy is effective in treating damaged endometrium. The current reports mainly focus on the therapeutic effects of stem cells through paracrine or transdifferentiation, respectively. This study investigates whether paracrine or transdifferentiation occurs preferentially in treating IUA.MethodsHuman amniotic mesenchymal stem cells (hAMSCs) and transformed human endometrial stromal cells (THESCs) induced by transforming growth factor beta (TGF-β1) were co-cultured in vitro. The mRNA and protein expression levels of Fibronectin (FN), Collagen I, Cytokeratin19 (CK19), E-cadherin (E-cad) and Vimentin were detected by Quantitative real-time polymerase chain reaction (qPCR), Western blotting (WB) and Immunohistochemical staining (IHC). The Sprague-Dawley (SD) rats were used to establish the IUA model. hAMSCs, hAMSCs-conditional medium (hAMSCs-CM), and GFP-labeled hAMSCs were injected into intrauterine, respectively. The fibrotic area of the endometrium was evaluated by Masson staining. The number of endometrium glands was detected by hematoxylin and eosin (H&E). GFP-labeled hAMSCs were traced by immunofluorescence (IF). hAMSCs, combined with PPCNg (hAMSCs/PPCNg), were injected into the vagina, which was compared with intrauterine injection.ResultsqPCR and WB revealed that FN and Collagen I levels in IUA-THESCs decreased significantly after co-culturing with hAMSCs. Moreover, CK19, E-cad, and Vimentin expressions in hAMSCs showed no significant difference after co-culture for 2 days. 6 days after co-culture, CK19, E-cad and Vimentin expressions in hAMSCs were significantly changed. Histological assays showed increased endometrial glands and a remarkable decrease in the fibrotic area in the hAMSCs and hAMSCs-CM groups. However, these changes were not statistically different between the two groups. In vivo, fluorescence imaging revealed that GFP-hAMSCs were localized in the endometrial stroma and gradually underwent apoptosis. The effect of hAMSCs by vaginal injection was comparable to that by intrauterine injection assessed by H&E staining, MASSON staining and IHC.ConclusionsOur data demonstrated that hAMSCs promoted endometrial repair via paracrine, preferentially than transdifferentiation.

Oral ulcer treatment using human tonsil-derived mesenchymal stem cells encapsulated in trimethyl chitosan hydrogel: an animal model study

BackgroundOral ulcers are a common side effect of chemotherapy and affect patients’ quality of life. While stem cell transplantation is a potential treatment for oral ulcers, its efficacy is limited as the stem cells tend to remain in the affected area for a short time. This study aims to develop a treatment for oral ulcers by using trimethyl chitosan (TMC) hydrogel with human tonsil-derived stem cells (hTMSCs) to increase the therapeutic effect of stem cells and investigate their effectiveness.MethodsAnimals were divided into four experimental groups: Control, TMC hydrogel, hTMSCs, and hTMSCs loaded in TMC hydrogel (Hydrogel + hTMSCs) (each n = 8). Oral ulcers were chemically induced by anesthetizing the rats followed by injection of dilute acetic acid in the right buccal mucosa. After confirming the presence of oral ulcers in the animals, a single subcutaneous injection of 100 µL of each treatment was applied to the ulcer area. Histological analyses were performed to measure inflammatory cells, oral mucosal thickness, and fibrosis levels. The expression level of inflammatory cytokines was also measured using RT-PCR to gauge therapeutic the effect.ResultsThe ulcer size was significantly reduced in the TMC hydrogel + hTMSCs group compared to the control group. The stem cells in the tissue were only observed until Day 3 in the hTMSCs treated group, while the injected stem cells in the TMC Hydrogel + hTMSCs group were still present until day 7. Cytokine analysis related to the inflammatory response in the tissue confirmed that the TMC Hydrogel + hTMSCs treated group demonstrated superior wound healing compared to other experimental groups.ConclusionThis study has shown that the adhesion and viability of current stem cell therapies can be resolved by utilizing a hydrogel prepared with TMC and combining it with hTMSCs. The combined treatment can promote rapid healing of oral cavity wounds by enhancing anti-inflammatory effects and expediting wound healing. Therefore, hTMSC loaded in TMC hydrogel was the most effective wound-healing approach among all four treatment groups prolonging stem cell survival. However, further research is necessary to minimize the initial inflammatory response of biomaterials and assess the safety and long-term effects for potential clinical applications.

Exosomes in renal cell carcinoma: challenges and opportunities.

Renal cell carcinoma (RCC) is the most common type of kidney cancer that accounts for approximately 2-3% of adult malignancies. Among the primary treatment methods for this type of cancer are surgery and targeted treatment. Still, due to less than optimal effectiveness, there are problems such as advanced distant metastasis, delayed diagnosis, and drug resistance that continue to plague patients. In recent years, therapeutic advances have increased life expectancy and effective treatment in renal cell carcinoma patients. One of these methods is the use of stem cells. Although the therapeutic effects of stem cells, especially mesenchymal stem cells, are still impressive, today, extracellular vesicles (EVs) as carrying molecules and various mediators in intercellular communications, having a central role in tumorigenesis, metastasis, immune evasion, and drug response, and on the other hand, due to its low immunogenicity and strong regulatory properties of the immune system, has received much attention from researchers and doctors. Despite the increasing interest in exosomes as the most versatile type of EVs, the heterogeneity of their efficacy presents challenges and, on the other hand, exciting opportunities for diagnostic and clinical interventions.In the upcoming article, we will review the various aspects of exosomes' effects in the prevention, treatment, and progress of renal cell carcinoma and also ways to optimize them to strengthen their positive sides.

Research advances on stem cell-based treatments in animal studies and clinical trials of lymphedema

To summarize the progress of the roles and mechanisms of various types of stem cell-based treatments and their combination therapies in both animal studies and clinical trials of lymphedema. The literature on stem cell-based treatments for lymphedema in recent years at home and abroad was extensively reviewed, and the animal studies and clinical trials on different types of stem cells for lymphedema were summarized. Various types of stem cells have shown certain effects in animal studies and clinical trials on the treatment of lymphedema, mainly through local differentiation into lymphoid endothelial cells and paracrine cytokines with different functions. Current research focuses on two cell types, adipose derived stem cells and bone marrow mesenchymal stem cells, both of which have their own advantages and disadvantages, mainly reflected in the therapeutic effect of stem cells, the difficulty of obtaining stem cells and the content in vivo. In addition, stem cells can also play a synergistic role in combination with other treatments, such as conservative treatment, surgical intervention, cytokines, biological scaffolds, and so on. However, it is still limited to the basic research stage, and only a small number of studies have completed clinical trials. Stem cells have great transformation potential in the treatment of lymphedema, but there is no unified standard in the selection of cell types, the amount of transplanted cells, and the timing of transplantation.

Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke: current evidence and future perspectives

Ischemic stroke is a leading cause of death and disability worldwide, with an increasing trend and tendency for onset at a younger age. China, in particular, bears a high burden of stroke cases. In recent years, the inflammatory response after stroke has become a research hotspot: understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment. This review summarizes several major cells involved in the inflammatory response following ischemic stroke, including microglia, neutrophils, monocytes, lymphocytes, and astrocytes. Additionally, we have also highlighted the recent progress in various treatments for ischemic stroke, particularly in the field of stem cell therapy. Overall, understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes. Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Applications of Mesenchymal Stem Cells in Treatments of Domestic Animals

Mesenchymal stem cells: they have received great attention in the field of regenerative medicine due to their ability to differentiate into different cell types and their ability to secrete a wide range of biologically active molecules that repair and regenerate tissues. Stem cells are usually isolated from bone marrow, adipose tissue, or other adult tissues and can be grown in culture media to generate large numbers of cells. Stem cells are widely used in veterinary medicine: for the treatment of bone diseases, diseases of the respiratory and digestive systems, immune diseases. The therapeutic effect of stem cells is due to the anti-inflammatory and immunomodulatory effects of the cells themselves and their excretory products. In general, the continuous investigation and development of Veterinary key therapies is essential to improve animal health and well-being, promote Translational Medicine, and thereby benefit human health. Mesenchymal stem cells have been studied as a potential treatment for various gastrointestinal diseases in cattle, including inflammatory bowel disease and Colitis. Stem cells can be used to replace damaged or diseased tissue by differentiating between specific cell types required for repair and regeneration. Stem cells can also secrete factors that promote tissue regeneration, which can enhance their therapeutic potential. Diverse alternatives provide an attractive option for the possibility of developing clinical applications of stem cells in veterinary medicine.

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

Signaling Mechanisms of Stem Cell Therapy for Intervertebral Disc Degeneration.

Low back pain is the leading cause of disability worldwide. Intervertebral disc degeneration (IDD) is the primary clinical risk factor for low back pain and the pathological cause of disc herniation, spinal stenosis, and spinal deformity. A possible approach to improve the clinical practice of IDD-related diseases is to incorporate biomarkers in diagnosis, therapeutic intervention, and prognosis prediction. IDD pathology is still unclear. Regarding molecular mechanisms, cellular signaling pathways constitute a complex network of signaling pathways that coordinate cell survival, proliferation, differentiation, and metabolism. Recently, stem cells have shown great potential in clinical applications for IDD. In this review, the roles of multiple signaling pathways and related stem cell treatment in IDD are summarized and described. This review seeks to investigate the mechanisms and potential therapeutic effects of stem cells in IDD and identify new therapeutic treatments for IDD-related disorders.

Stem cell therapies for periodontal tissue regeneration: A meta-analysis of clinical trials

ObjectiveStem cell therapy in periodontal tissue regeneration has reported optimistic regenerative results; evidence supporting its superiority over conventional methods is still ambiguous. Therefore, this meta-analysis aims to evaluate the therapeutic effects of stem cells in human periodontal regeneration. DesignA literature search was conducted to retrieve relevant articles on periodontal regeneration in stem cell therapy. A meta-analysis of the studies was conducted using the Stata software. ResultsFifteen studies that examined the effect of stem cell therapies on periodontal tissue regeneration in 369 patients were selected from databases. Regardless of the various types of cells, both odontogenic (periodontal ligament, dental pulp, gingiva stem cell) and non-odontogenic (bone marrow, periosteum-derived, and umbilical cord stem cells), the cell therapies witnessed significant improvements in terms of clinical attachment level (SMD, −0.67; 95CI, −0.90 to −0.43), probing depth (SMD, −0.76; 95% CI, −1.21 to - 0.31), radiographic intrabony defect depth (SMD, −0.87; 95% CI, −1.52 to −0.23), and histomorphometric analysis of mineralized bone (SMD, 0.80; 95% CI, 0.42 to 1.19) when compared to traditional without-cell treatment in patients. However, evidence on gingival recession, alveolar thickness gain, bone mineral density of bone core, and bone volume fraction of bone core outcomes did not reach statistical significance. ConclusionsEvidence suggests that the implementation of stem cell therapies in reconstructing compromised gingiva and alveolar bone tissue produces positive outcomes compared with conventional approaches. However, further well-designed investigations are needed to comprehensively identify the most effective source of cells and biomaterials for each case.

Probing Gut Participation in Parkinson's Disease Pathology and Treatment via Stem Cell Therapy.

Accumulating evidence suggests the critical role of the gut-brain axis (GBA) in Parkinson's disease (PD) pathology and treatment. Recently, stem cell transplantation in transgenic PD mice further implicated the GBA's contribution to the therapeutic effects of transplanted stem cells. In particular, intravenous transplantation of human umbilical-cord-blood-derived stem/progenitor cells and plasma reduced motor deficits, improved nigral dopaminergic neuronal survival, and dampened α-synuclein and inflammatory-relevant microbiota and cytokines in both the gut and brain of mouse and rat PD models. That the gut robustly responded to intravenously transplanted stem cells and prompted us to examine in the present study whether direct cell implantation into the gut of transgenic PD mice would enhance the therapeutic effects of stem cells. Contrary to our hypothesis, results revealed that intragut transplantation of stem cells exacerbated motor and gut motility deficits that corresponded with the aggravated expression of inflammatory microbiota, cytokines, and α-synuclein in both the gut and brain of transgenic PD mice. These results suggest that, while the GBA stands as a major source of inflammation in PD, targeting the gut directly for stem cell transplantation may not improve, but may even worsen, functional outcomes, likely due to the invasive approach exacerbating the already inflamed gut. The minimally invasive intravenous transplantation, which likely avoided worsening the inflammatory response of the gut, appears to be a more optimal cell delivery route to ameliorate PD symptoms.

Pharmacological Inhibition of the Asparaginyl Endopeptidase (AEP) in an Alzheimer's Disease Model Improves the Survival and Efficacy of Transplanted Neural Stem Cells.

Stem-cell-based therapy is very promising for Alzheimer's disease (AD), yet has not become a reality. A critical challenge is the transplantation microenvironment, which impacts the therapeutic effect of stem cells. In AD brains, amyloid-beta (Aβ) peptides and inflammatory cytokines continuously poison the tissue microenvironment, leading to low survival of grafted cells and restricted efficacy. It is necessary to create a growth-supporting microenvironment for transplanted cells. Recent advances in AD studies suggest that the asparaginyl endopeptidase (AEP) is a potential intervention target for modifying pathological changes. We here chose APP/PS1 mice as an AD model and employed pharmacological inhibition of the AEP for one month to improve the brain microenvironment. Thereafter, we transplanted neural stem cells (NSCs) into the hippocampus and maintained therapy for one more month. We found that inhibition of AEPs resulted in a significant decrease of Aβ, TNF-α, IL-6 and IL-1β in their brains. In AD mice receiving NSC transplantation alone, the survival of NSCs was at a low level, while in combination with AEP inhibition pre-treatment the survival rate of engrafted cells was doubled. Within the 2-month treatment period, implantation of NSCs plus pre-inhibition of the AEP significantly enhanced neural plasticity of the hippocampus and rescued cognitive impairment. Neither NSC transplantation alone nor AEP inhibition alone achieved significant efficacy. In conclusion, pharmacological inhibition of the AEP ameliorated brain microenvironment of AD mice, and thus improved the survival and therapeutic efficacy of transplanted stem cells.

Mesenchymal Stem Cells in the Treatment of Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD) and the AKI-to-CKD Transition

ABSTRACT Acute kidney injury (AKI) and chronic kidney disease (CKD) are global health burdens that result in high economic costs to healthcare systems. AKI is a known risk factor for progression to CKD. The global absolute CKD prevalence increased by 28.2% from 2007–2017 among females and 25.4% among males. Current best clinical practice only slows the progress of renal fibrosis, the final pathological consequence of renal injury, in CKD. Kidney transplantation and dialysis are the only options for the management of kidney failure, which results in a significant burden on the health system. Hence innovative strategies are urgently needed to both prevent and treat CKD. Many studies have demonstrated that mesenchymal stem cells (MSCs) exert a therapeutic role through regenerating/repairing damaged tissues primarily through cargo secreted in extracellular vesicles. In recent years, the therapeutic effect of stem cells in the treatment of acute and chronic kidney disease have been primarily assessed in preclinical studies. This review outlines the safety and efficacy of MSCs in AKI, CKD and the AKI-to-CKD transition based on recent animal studies and clinical trials. It elucidates the antifibrotic mechanisms of MSCs and provides novel insights into MSC therapy in AKI, CKD and the transition from AKI to CKD.

Preparation and Validation of Zebrafish Psoriasis Model to Investigate the Therapeutic Effects of Stem Cells.

Psoriasis is a chronic, inflammatory, autoimmune disease with systemic symptoms including seborrheic psoriasis, pustular lesions, plaque lesions, intestinal eruptions, and sometimes arthritis. Moreover, most of the psoriatic subjects report life challenges due to the condition, impacting social activities and daily tasks. Generally, psoriasis treatment options depend on the severity, coexisting conditions, and medical availability. Although psoriasis therapies reduce symptoms and appearance, still it is not curable. Hereupon, searching for optimal therapeutic options continues. Accordingly, stem cell therapy is considered an advanced psoriasis treatment. Subsequently, stem cell therapies' efficacy is uncertain yet. Therefore, further studies are needed. In this context, preclinical studies such as animal experiments are essential for evaluation of treatment modalities. Herein, zebrafish offer advantages in testing treatments and biomedical research applications compared to other vertebrate models. Further, zebrafish skin shares similarities with human skin, making it suitable for studying inflammatory disorders. Hence, the authors discuss the zebrafish psoriasis development method for evaluating the stem cell therapeutic influence.

Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing

Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in a wound-healing model. Dual CXCR4 and IL-10 genes were inserted into the AMM genome using transcription-activator-like effector nuclease (TALEN). Matrigel tube formation and anti-inflammatory effects were assessed in vitro, and efficacy was tested in vivo in a diabetic wound-healing model. CXCR4/IL-10-expressing amniotic MSCs (AMM/CI) strongly expressed CXCR4 and IL-10 genes and robustly promoted tube formation and anti-inflammatory potential. AMM/CI transplantation resulted in accelerated wound healing, as well as high engraftment and re-epithelialization potential. Transplanted AMM/CI also exhibited high angiogenic and decreased pro-inflammatory gene expression in the wound tissue, indicating direct therapeutic effects on wound healing. Taken together, these data indicate that dual angiogenic/anti-inflammatory gene knock-in may be a novel approach to enhance the therapeutic effects of stem cells, and transplantation of AMM/CI can be an alternative therapeutic option in chronic wound healing.

Evaluation of the Efficacy of Stem Cell Therapy in Animal Models of Intervertebral Disc Degeneration Based on Imaging Indicators: A Systematic Review and Meta-Analysis.

Objective The purpose of this study is to make a systematic review of the therapeutic effect of stem cells in animal models of disc degeneration from an imaging point of view. Methods Data were extracted by searching electronic databases for RCTs that met the inclusion criteria. Data analysis was performed using RevMan 5.3 and STATA 15.1 software. This meta-analysis was registered with INPLASY, registration number INPLASY202240148. Results A total of 34 studies were included, covering four species of animals, rabbits, sheep, rats, and mice, with a total of 1163 intervertebral discs. In terms of DHI, the efficacy of stem cell group in rabbits (P < 0.001), mice (P < 0.001), sheep (P < 0.001), and rats (P = 0.001) was better than that in control group. In terms of disc height, the efficacy of stem cell group in rats (P < 0.001) was better than that in control group, while in sheep (P = 0.355), there was no statistical difference between two groups. In terms of MRI index, the efficacy of stem cell group in rats (P < 0.001), mice (P < 0.001), and rabbits (P = 0.016) was better than that in control group. In terms of MRI signal score, the efficacy of stem cell group in rabbits (P < 0.001) was better than that of control group. In terms of T2 signal intensity, stem cell group was more effective than control group in rabbits (P < 0.001), mice (P < 0.001), and rats (P = 0.003).Conclusion Stem cell therapy can improve intervertebral disc-related imaging parameters in animal models of disc degeneration, indicating that stem cell therapy has a repairing effect on intervertebral discs. However, given the heterogeneity and limitations of this study, this conclusion still needs to be tested by a large number of studies.

Combination stem cell therapy using dental pulp stem cells and human umbilical vein endothelial cells for critical hindlimb ischemia

Narrowing of arteries supplying blood to the limbs provokes critical hindlimb ischemia (CLI). Although CLI results in irreversible sequelae, such as amputation, few therapeutic options induce the formation of new functional blood vessels. Based on the proangiogenic potentials of stem cells, in this study, it was examined whether a combination of dental pulp stem cells (DPSCs) and human umbilical vein endothelial cells (HUVECs) could result in enhanced therapeutic effects of stem cells for CLI compared with those of DPSCs or HUVECs alone. The DPSCs+ HUVECs combination therapy resulted in significantly higher blood flow and lower ischemia damage than DPSCs or HUVECs alone. The improved therapeutic effects in the DPSCs+ HUVECs group were accompanied by a significantly higher number of microvessels in the ischemic tissue than in the other groups. In vitro proliferation and tube formation assay showed that VEGF in the conditioned media of DPSCs induced proliferation and vessel-like tube formation of HUVECs. Altogether, our results demonstrated that the combination of DPSCs and HUVECs had significantly better therapeutic effects on CLI via VEGF-mediated crosstalk. This combinational strategy could be used to develop novel clinical protocols for CLI proangiogenic regenerative treatments.

The therapeutic effect of stem cells from human exfoliated deciduous teeth on a rat model of tracheal fistula

BackgroundTracheal fistulas (TF) can be dangerous and even fatal in patients. The current treatment is really challenging. Previous studies reported that mesenchymal stem cells (MSCs) could be used to treat respiratory tract fistulas. Stem cells from human exfoliated deciduous teeth (SHED) are considered to be MSC-like cells that may also have the potential to treat the tracheal fistulas. In this study, we investigated the therapeutic effects of SHED in rat tracheal fistula models.MethodsA total of 80 SD rats were randomly divided into five groups: a sham-operated group, a local PBS group (L-PBS), an intravenous PBS group (I-PBS), a local SHED treatment group (L-SHED), and an intravenous SHED treatment group (I-SHED). The L-SHED and I-SHED groups were given a topical application around the fistula or an intravenous injection of 1*107 SHED via the tail vein, respectively, while the L-PBS and I-PBS groups were given an equivalent volume of PBS through local or intravenous administration. A stereomicroscope was used to observe fistula healing on the 2nd, 3rd, and 5th days following transplantation. On the 7th day, the survival of SHED was observed by immunofluorescence. The pathology of the lungs and fistulas was observed by hematoxylin and eosin (H&E) and Masson staining. The expression levels of the Toll-like receptor 4 (TLR4), interleukin (IL)-1β, IL-33, and IL-4 were measured using immunohistochemistry. The expression levels of TLR4, high mobility group box 1 (HMGB1), and myeloid differentiation factor 88 (MYD88) were studied using western blotting. On day 14, airway responsiveness of rats was detected and analyzed.ResultsFistula healing in the L-SHED and I-SHED groups was faster than that in their respective PBS groups after transplantation. The fistula diameters in the L-SHED and I-SHED groups were significantly smaller than those in the L-PBS and I-PBS groups on the 3rd day. Moreover, the phenomenon of fibroblast proliferation and new blood vessel growth around the fistula seemed more pronounced in the L-SHED and I-SHED groups. Although no discernible difference was found in airway responsiveness after SHED treatment, the degree of inflammation in the lungs was reduced by intravenous SHED treatment. However, there was no significant reduction in lung inflammation by local SHED treatment. The expression levels of IL-1β and IL-33 were decreased in the I-SHED group, while IL-4 was elevated compared with the I-PBS group. Interestingly, intravenous SHED treatment inhibited the activation of HMGB1/TLR4/MYD88 in the lung tissues of TF rats.ConclusionsSHED transplantation accelerated the rate of fistula healing in rats. Intravenous SHED treatment reduced lung inflammation. Thus, SHED may have potential in the treatment of tracheal fistula, providing hope for future therapeutic development for TF.

The Antisenescence Effect of Exosomes from Human Adipose-Derived Stem Cells on Skin Fibroblasts.

Human adipose-derived stem cells (ADSCs) have become a promising therapeutic approach against skin aging. Recent studies confirm that exosomes partially mediate the therapeutic effect of stem cells. This study successfully isolated exosomes from the ADSC culture medium and discovered that ADSC-derived exosomes (ADSC-Exos) could alleviate human dermal fibroblast (HDF) senescence and stimulate HDF migration. Moreover, ADSC-Exos increased the type I collagen expression level and reduced the reactive oxygen species (ROS) and senescence-associated β-galactosidase (SA-β-Gal) activity in HDFs. In addition, we demonstrated that ADSC-Exos significantly inhibited senescence-related protein expression levels of p53, p21, and p16. In conclusion, our results have revealed the antisenescence effects of ADSC-Exos on HDFs and ADSC-Exos may be a novel cell-free therapeutic tool for antiaging.

Stem cell therapy for pulmonary arterial hypertension: An update.

Pulmonary arterial hypertension (PAH) remains a deadly disease, and there currently is no cure for this life-threating medical problem. The average lifespan is about 5 to 7 years after diagnosis of PAH. Therefore, a conceptual breakthrough to develop new therapeutic strategies for PAH is urgently needed. Growing evidence shows that stem cells are emerging as a novel effective treatment, but the understanding of its underlying mechanisms is still limited. This review highlights the mechanisms through which stem cells successfully reverse pulmonary vascular endothelial dysfunction, pulmonary artery smooth muscle cell over-proliferation, and mitochondrial dysfunction in PAH patients and common rodent models used in PAH research. They can modulate common underlying pathways involved in PAH, including the nitric oxide synthase, mitochondrial regulators, microRNAs and STAT3-BMPR signaling. Genetic modifications further enhance the therapeutic effects of stem cells on PAH. Clinical trials showed promising therapeutic potential of mesenchymal stem cells and endothelial progenitor cells for PAH. Potential limitations and challenges are also discussed. The current findings support the need for further investigation and validation of stem cell therapy for PAH.

A Review of Recent Advances in Nanomaterial-based Stem Cell Therapy and the Corresponding Risks

Stem cell therapy is widely regarded as a promising strategy in regenerative medicine, yet the therapeutic effects of stem cells in vivo are limited by many factors when applied without additional factors, such as poor cell engraftment, uncontrolled differentiation, and unclear cell fates and niches. The emergence of nanotechnology has provided several solutions for these problems. Nanomaterial-based cell labeling and tracking have been extensively investigated in recent decades, and many innovative and multifunctional nanomaterials have been used to reveal the fate of stem cells, allowing more efficient, sensitive, and accurate imaging/tracking strategies for stem cells to be achieved. Nanomaterials enhance stem cell therapy by incorporating or integrating with stem cells and, as scaffolds or substrates, nanomaterials with antioxidant properties that can be used as graft coatings show great promise for clinical transformation. However, current reviews on the subject tend to focus on the various effects of nanomaterials on stem cells and are less concerned with their application to stem cell therapy. Accordingly, we herein present a review of progress in the application of nanomaterials in stem cell therapy over the last three years, which we hope will be of benefit to a comprehensive understanding of nanomaterial-mediated stem cell therapy from lab to pre-clinical practice.