American journal of stem cells最新文献

Polycystic ovary syndrome (PCOS) presents distressing symptoms and stands as a primary cause of infertility. Currently, treatment options are limited to symptom management. This article presents a case study of a patient suffering from hair thinning associated with PCOS, treated with intravenous and subdermal injections of umbilical cord-derived mesenchymal stem cells (UC-MSCs). Remarkably, following treatment, the patient's 14-year history of menstrual irregularities and hormonal imbalances completely resolved, alongside the disappearance of ovarian cysts, with these improvements persisting for well over a year. Given PCOS's recognized inflammatory nature and the potent anti-inflammatory properties of UC-MSCs, we propose inflammation modulation as the likely mechanism of action. Further exploration is underway, actively seeking additional PCOS patients to ascertain whether similar therapeutic effects are reproducible or if this case represents an anomaly. This case underscores the potential of stem cell therapy as a revolutionary approach to PCOS management, addressing symptomatic relief and potentially underlying pathogenic mechanisms. The sustained clinical benefits observed advocate for comprehensive investigation into the efficacy and mechanisms of stem cell therapy in PCOS management.

Background: The use of dental pulp stem cells (DPSCs) in clinical applications instead of bone marrow stem cells is a very promising method capable of significantly changing the future of medical treatment. If further studies prove that DPSCs and the cells differentiated from them do not stimulate the immune system, these cells can be used more reliably in treatment of autoimmune diseases.

Methods: In this research, we examined the isolated DPSCs and differentiated osteoblasts from them in medium without inflammatory stimulants in terms of TLR3 and TLR4 gene expression and inflammatory cytokines, including TNF-α and IL-8 using qRT-PCR, and measured the concentration of inflammatory cytokines IL-8 and TNF-α produced by these two types of cells through ELISA.

Results: The obtained results showed that the expression level of inflammatory cytokines IL-8 and TNF-α in differentiated osteoblasts is significantly different as compared with DPSCs. However, no significant difference was observed in TLR-4 expression between two groups. An increase in TNF-α expression level was found to directly correlate with an increase in the expression of IL-8. The concentration of cytokine TNF-α in osteoblasts was significantly higher than that of IL-8 in DPSCs.

Conclusion: In comparison to DPSCs, osteoblast cells first lead to inflammatory responses. These responses reduce overtime. However, DPSCs retain their immunomodulatory properties and do not show inflammatory responses.

Sensorineural deafness mainly occurs due to damage to hair cells, and advances in stem cell technology, especially the application of induced pluripotent stem cells (iPSCs) and adult stem cells, provides new possibilities for hair cell regeneration. This review describes the basic knowledge of stem cells and their important applications in regenerative medicine, as well as recent progress in stem cell research in the field of hair cell regeneration, especially the induced differentiation of hair-like cells. At the same time, we also point out the challenges facing current research, including differentiation efficiency, cell stability issues, and treatment safety and long-term efficacy considerations. Finally, we look forward to the direction of future research, and emphasize the importance of the cell differentiation mechanism, simulation of the inner ear microenvironment, safety assessment, and personalized treatment strategies. In conclusion, despite many challenges, stem cell technology has shown great potential in the field of hearing research and is expected to bring revolutionary treatment options for patients with sensorineural hearing loss in the future.

Idiopathic pulmonary fibrosis (IPF) is an interstitial, fibrotic lung disease characterized by progressive damage. Lung tissues with IPF are replaced by fibrotic tissues with increased collagen deposition, modified extracellular matrix, all which overall damages the alveoli. These changes eventually impede the gas exchange function of the alveoli, and eventually leads to fatal respiratory failure of the lung. Investigations have been conducted to further understand IPF's pathogenesis, and significant progress in understanding its development has been made. Additionally, two therapeutic treatments, Nintedanib and Pirfenidone, have been approved and are currently used in medical applications. Moreover, cell-based treatments have recently come to the forefront of developing disease therapeutics and are the focus of many current studies. Furthermore, a sizable body of research encompassing basic, pre-clinical, and even clinical trials have all been amassed in recent years and hold a great potential for more widespread applications in patient care. Herein, this article reviews the progress in understanding the pathogenesis and pathophysiology of IPF. Additionally, different cell types used in IPF therapy were reviewed, including alveolar epithelial cells (AECs), circulating endothelial progenitors (EPCs), mixed lung epithelial cells, different types of stem cells, and endogenous lung tissue-specific stem cells. Finally, we discussed the contemporary trials that employ or explore cell-based therapy for IPF.

Objectives: This study investigated the therapeutic potential of fetal progenitor cells (FPCs) in the treatment of chronic non-healing wounds and ulcers associated with chronic limb ischemia (CLI). The research aimed to elucidate the mechanism of action of FPCs and evaluate their efficacy and safety in CLI patients.

Methods: The researchers isolated FPCs from aborted human fetal liver, brain, and skin tissues and thoroughly characterized them. The preclinical phase of the study involved assessing the effects of FPCs in a rat model of CLI. Subsequently, a randomized controlled clinical trial was conducted to compare the efficacy of FPCs with standard treatment and autologous bone marrow mononuclear cells in CLI patients. The clinical trial lasted 12 months, with a follow-up period of 24-36 months. The primary outcomes included wound healing, frequency of major and minor amputations, pain reduction, and the incidence of complications. Secondary outcomes involved changes in local hemodynamics and histological, ultrastructural, and immunohistochemical assessments of angiogenesis.

Results: In the animal model, FPC treatment significantly enhanced angiogenesis and accelerated healing of ischemic wounds compared to controls. The clinical trial in CLI patients demonstrated that the FPC therapy achieved substantially higher rates of complete wound closure, prevention of major amputation, pain reduction, and improvement in ankle-brachial index compared to control groups. Notably, the study reported no serious adverse events.

Conclusions: FPC therapy exhibited remarkable efficacy in promoting the healing of ischemic wounds, preventing amputation, and improving symptoms and quality of life in patients with CLI. The proangiogenic and provasculogenic effects of FPCs may be attributed to their ability to secrete specific growth factors. These findings provide new insights into the development of cellular therapeutic angiogenesis as a promising approach for the treatment of peripheral arterial diseases.

Post-corneal transplantation endothelial decompensation and subsequent bullous keratopathy often result in unfavorable clinical outcomes regardless of the treatment strategy employed. In this report, we present the outcomes of a patient managed with in vitro expanded human corneal endothelial cell (HCEC) transplantation facilitated by a nanocomposite gel (NC gel) sheet over 16 years. A 40-year-old male patient who presented with signs of graft failure after penetrating keratoplasty underwent HCEC transplantation. Additionally, HCECs were obtained from a deceased donor, cultured in vitro, and transplanted onto an NC gel sheet as a temporary scaffold to support the transplanted cells until engraftment. At the 16-year follow-up, the cornea had remained stable and did not exhibit active disease manifestations. Notably, no new bullae were formed, and the epithelial surface appeared smooth without signs of active fluid transport abnormalities. Although a slight reduction in corneal thickness was observed, the disease-free region at the time of the intervention remained transparent. HCEC transplantation with NC gel sheets is a promising, minimally invasive approach for achieving long-term corneal stability in cases of bullous keratopathy following corneal graft failure. Importantly, this technique circumvents the need for complex procedures and utilizes corneal endothelial precursors derived from donor corneas discarded for lack of sufficient endothelial cells. After in vitro culture, these cells were successfully transplanted in three patients, proving that one donated eye can be useful in treating three eyes of three patients. This technique addresses the donor cornea shortage concerns and makes our concept "an-eye-for-eyes", a reality.

Background: Replacing damaged organs or tissues and repairing damage by tissue engineering are attracting great interest today. A potentially effective method for bone remodeling involves combining nanofiber scaffolds with extracellular matrix (ECM), and growth factors. Today, electrospun PCL-based scaffolds are widely used for tissue engineering applications.

Methods: In this study, we used an electrospun polycaprolactone (PCL) scaffold coated with fibronectin (Fn), a ubiquitous ECM glycoprotein, to investigate the induction potential of this scaffold in osteogenesis with adipose-derived mesenchymal stem cells (AD-MSCs).

Results: Scanning electron microscopy (SEM) analysis showed that fibronectin, by binding to the membrane receptors of mesenchymal stem cells (MSCs), leads to their attachment and proliferation on the PCL scaffold and provides a suitable environment for osteogenesis. In addition, biochemical tests showed that fibronectin leads to increased calcium deposition. The results also showed that alkaline phosphatase activity was significantly higher in the PCL scaffold coated with fibronectin than in the control groups (PCL scaffold group and tissue culture polystyrene (TCPS) group) (P<0.05). Also, the analysis of quantitative reverse transcription PCR (qRT-PCR) data showed that the relative expression of bone marker genes such as osteonectin (ON), osteocalcin (OC), RUNX family transcription factor 2 (RUNX2), and collagen type I alpha 1 (COL1) was much higher in the cells seeded on the PCL/Fn scaffold than in the other groups (P<0.05).

Conclusions: The results show that fibronectin has an increasing effect in accelerating bone formation and promising potential for use in bone tissue engineering.

Objectives: This study aimed to investigate the effect of acoustic vibration on the pluripotency of human embryonic stem cells (hESCs) and evaluate cell proliferation and self-renewal ability post-treatment.

Methods: The human ES cell line H1 was used for the experiments. hESCs were treated with an acoustic vibration device. Their proliferative ability was subsequently detected using a colony formation assay, while the expression of pluripotency-related markers was detected via immunofluorescence staining. Finally, changes in gene expression levels were examined using quantitative polymerase chain reaction (qPCR) in the presence of appropriate primers.

Results: Compared with normal cells in the control group, the morphology of experimental cells subjected to acoustic vibration did not significantly change. Contrastingly, the colony-forming efficiency of the experimental cells significantly increased. Immunofluorescence staining results showed the cells in experimental group were positive for the pluripotency markers NANOG, octamer-binding transcription factor 4 gene (OCT4), and SRY (sex determining region Y)-box 2 (SOX2). In addition, the expression levels of pluripotency genes NANOG, OCT4, SOX2, and Yes-associated protein (YAP)-related genes were up-regulated following acoustic vibration.

Conclusions: Our results revealed that acoustic vibration enhanced the proliferative ability of hESCs and increased the expression levels of NANOG, OCT4, SOX2, and YAP-related genes, indicating that acoustic vibration can optimize the self-renewal ability of hESCs and that the YAP signaling pathway may play a critical role in the functional process of acoustic vibration.

Dentin-pulp regeneration through stem/progenitor cell transplantation represents a promising frontier in regenerative endodontics. This systematic review meticulously evaluates animal studies to investigate the efficacy of stem cell therapy in repairing/regenerating the dentine-pulp complex in mature/immature animal teeth. Employing a comprehensive electronic search of PubMed and Scopus databases up to October 2023, relevant English studies were identified/assessed. Evaluation parameters encompassed radiographic and histological assessments of dentin-pulp complex formation. Outcome measures included pulp-like and dentin-like tissues regeneration, apical healing, dentin thickening, apical closure, and dentinal bridge formation. The risk-of-bias assessment adhered to the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) guidelines. Out of 3250 identified articles, 23 animal experiments were included, categorized into regenerative procedures in mature teeth (n=11), regenerative procedures in immature teeth (n=4), and vital pulp therapy (n=8). Despite the promising potential, the bias in the included studies was high. Notably, Various scaffolds, and growth factors were employed, highlighting the heterogeneity across the studies. Dental pulp stem cells (DPSCs) and bone marrow stem cells, especially specific subfractions, demonstrated notable regenerative potential: hypoxic conditions and extracellular vesicles from preconditioned DPSCs enhanced regeneration, with considerations of cell fate. Donor age impacted regeneration, and challenges persisted in pulpotomy and direct pulp capping. Scaffold and growth factor choices influenced outcomes, underscoring the need for standardized strategies. Despite the promise, clinical viability faces hurdles, necessitating further investigation into adverse effects, optimized scaffolds, and regulatory considerations. This systematic review illuminates the potential of stem cell transplantation for dentin-pulp complex regeneration. The overall evidence quality, influenced by study heterogeneity and biases, underscores the need for cautious interpretation of findings. Future studies should refine methodologies and establish reliable histological parameters for meaningful advancements in dentin-pulp regeneration.

This systematic review evaluates clinical studies investigating regenerative endodontic procedures for mature/immature teeth utilizing stem cell transplantation. An electronic search of Scopus, PubMed, ISI Web Science, and Google Scholar was conducted up to January 2023. Outcome measures encompassed radiographic (periapical lesion, root length, apical foramen width, volume of the regenerated pulp) and clinical (post-operative pain, sensibility test) parameters. Among 3250 identified articles, five clinical studies were selected, comprising two randomized controlled trials (RCTs) for mature/immature teeth, and three case reports/series for mature teeth. Despite the promising potential, the included studies exhibited a notable risk of bias. The diversity in stem cells (e.g., dental pulp stem cells [DPSCs], umbilical cord mesenchymal stem cells [UC-MSCs]), scaffolds (Atecollagen, collagen membrane, platelet-poor plasma [PPP], leukocyte platelet-rich in fibrin [L-PRF]), and growth factors (granulocyte colony-stimulating factor [G-CSF]) emphasized the heterogeneity across interventions. In RCTs, DPSCs application increased root length and reduced apical foramen width in immature teeth, while UC-MSCs transplantation reduced apical lesions in mature teeth. Transplantation of DPSCs aggregates or UC-MSCs/PPP also elicited positive pulp responses and increased blood flow. In case reports/series, DPSCs application in teeth with irreversible pulpitis resulted in mineralization and increased the regenerated pulp' volume. Furthermore, transplantation of DPSCs with G-CSF/atelocollagen or L-PRF/collagen membrane led to positive pulp responses. While underscoring the potential of stem cell transplantation for regenerative endodontics in mature/immature teeth, the overall evidence quality and the limited number of available studies emphasize the need for cautious interpretation of results. Future well-designed clinical studies are essential to validate these findings further.