Latest ArticlesStem cell therapy offers promise for the neurodegenerative diseases and has been explored for sensorineural hearing loss (SNHL). However, effective cell delivery strategies remain a critical challenge for SNHL treatment.
To address this need, we established an ouabain-induced SGN injured hearing loss model in rat and evaluated a novel transplantation strategy targeting the cochlear nerve surface via posterior occipital approach, designed to minimize cochlear structural damage and facilitate targeted cell delivery to Rosenthal's canal (RC). The temporal changes in glial cell densities within RC revealed a progressively deteriorating neural microenvironment, supporting early-stage intervention. Accordingly, hair follicle-derived neural crest stem cell (HFNCSC) transplantation was performed 3 or 4 days after modeling via two approaches: cochlear nerve surface transplantation (CNT) and round window transplantation (RWT).
CNT resulted in significant improvements in auditory function, as evidenced by reduced auditory brainstem response (ABR) thresholds, shortened wave I latencies, and preserved wave I amplitudes post-transplantation. Transplanted cells were distributed along the nerve trunk and within RC. In contrast, RWT failed to improve auditory function and caused cochlear structural damage, with widespread cell dispersion in cochlear fluids. Notably, the CNT group exhibited significantly higher densities of TUJ1-positive neuron-like cells and glial cells in the RC, accompanied by enhanced myelin basic protein expression suggestive of remyelination. No such improvements were observed in the RWT group.
These findings suggest that cochlear nerve surface transplantation enhances stem cell survival and auditory function recovery, and represents a promising delivery approach for stem cell-based therapy of SGN-related hearing loss.
Excessive extracellular matrix accumulation, primarily as a result of hepatic stellate cell activation, is a hallmark of hepatic fibrosis, a progressive outcome of chronic liver injuries. Recent research studies suggest that stem cells, hepatocytes, and extracellular vesicles may provide therapeutic advantages due to their anti-inflammatory, antioxidative, and regenerative activities. This study aimed to comparatively evaluate the therapeutic efficacy of these agents in a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis.
Liver fibrosis was induced in male Wistar rats via intraperitoneal CCl4 injections for 8 weeks. Then the animals were intravenously administrated stem cells, hepatocytes, hepatocyte-derived exosomes, or stem cell-derived exosomes. Also, a fibrosis, a sham, a intact, and a PBS-treated group were consider the controls. After treatment, protein expression (alpha-smooth muscle actin (α-SMA), desmin), oxidative stress markers (superoxide dismutase, glutathione peroxidase, malondialdehyde), serum biochemical parameters (aspartate aminotransferase, alanine aminotransferase, glucose, uric acid, cholesterol, triglycerides), and fibrosis-related gene expression (matrix metalloproteinase 2 (MMP2), platelete-derived growth factor receptor beta (PDGFRB), transforming growth factor-beta (TGF-β), thymosin beta-10 (TMSB10) and transmembrane protein 176B (TMEM176B)) were assessed.
Significant liver damage, changed metabolic parameters, increased oxidative stress, and upregulated fibrosis markers were all observed in the fibrosis group. On the contrary, all treatments caused considerable improvements, though exosomes derived from stem cells demonstrated the most significant effects. Along with improved histopathological features, this group exhibited significant decreases in oxidative damage, liver enzymes, and profibrotic marker expression.
Liver fibrosis was considerably reduced by stem cells, hepatocytes, and particularly their exosomes. Exosomes made from stem cells demonstrated the strongest therapeutic effect, confirming their potential as a viable noncellular hepatic fibrosis treatment approach.
This study aims to establish a theoretical foundation for selecting and constructing animal models in clinical research on spine-related diseases. By establishing surgical models in three experimental animal species—mice, rats, and rabbits—we compare their respective advantages and disadvantages. First, three experimental animals of each of the three species were selected in good health. Subsequently, the experimental animals were dissected and several indices of the designated intervertebral discs and the height of the adjacent vertebrae were measured. At the same time, the ease of the surgical operation was assessed intraoperatively (in terms of the ease of preoperative localization, the clarity of the intraoperative structures, and the length of the surgical operation). In addition, the animal type most suitable for the construction of a spinal fusion surgery model was evaluated. Finally, a rabbit spinal fusion surgical model was constructed and evaluated by palpation and gross view of the tissue to assess the degree of spinal fusion. The data on the disc structure of rabbits have more advantages than those of mice and rats in constructing surgical models, with easier preoperative localization, more precise intraoperative structure, and shorter surgery time. Spinal fusion surgery in rabbits was successful, with a significant trend toward fusion at 4 weeks postoperatively. Rabbits were superior to mice and rats as experimental animals for establishing spinal fusion surgery models, and the fusion models were effective.
Age-related macular degeneration (AMD) is a multifactorial retinal disease in which alterations in lipid metabolism and dysregulation of the complement system play a central role. The aim of this study was to characterize a novel double-knockout (DK) mouse model deficient in apolipoprotein E and complement factor H (ApoE−/−Cfh−/−) as an experimental model of early and intermediate AMD.
ApoE−/−Cfh−/− mice and wild-type controls underwent comprehensive morphological, ultrastructural, biochemical, and molecular analyses. Retinal and retinal pigment epithelium (RPE) integrity, Bruch's membrane (BM) morphology, lipid accumulation, complement activation, angiogenic signaling, and synaptic organization were evaluated using histology, electron microscopy, immunohistochemistry, biochemical assays, and gene expression analyses.
DK mice exhibited significant RPE thinning, disruption of tight junctions, vacuolization, and BM thickening (p < 0.05). Lipid accumulation and plasma lipid levels significantly increased compared with controls (p < 0.01). Complement activation was significantly enhanced, as evidenced by increased C5b-9 deposition (p < 0.01). In addition, DK mice exhibited increased vascular endothelial growth factor expression (p < 0.05), altered matrix metalloproteinase activity (p < 0.05), and significant synaptic disorganization between photoreceptors and second-order neurons (p < 0.05).
The ApoE−/−Cfh−/− mouse reproduces key molecular and structural features of early and intermediate retinal degeneration with statistically significant alterations. Although it does not progress to advanced disease stages, it represents a valuable model to investigate several factors of AMD pathogenesis and evaluate therapeutic strategies targeting early disease mechanisms.
Transplantation of insulin-producing cells derived from pluripotent stem cells represents a highly promising approach for the radical treatment of type 1 diabetes (T1D). Informed by a comprehensive understanding of fetal pancreatic development, directed differentiation protocol for generating pancreatic β cells from pluripotent stem cells has been established and has achieved considerable advances, enabling the production of mature, fully functional β cells that closely recapitulate the characteristics of native pancreatic β cells. Preclinical studies have shown that the transplantation of stem cell-derived islets (SC-islets) reverses hyperglycemia in both mouse and nonhuman primate models, with a favorable safety profile. Early-phase clinical trials have further corroborated the safety and efficacy of this approach, a subset of patients with long-standing T1D achieved insulin independence, described as a "functional cure", with no serious adverse events of clinical significance reported. Despite these encouraging results, substantial challenges remain. With respect to differentiation protocols, insufficient functional maturity, pronounced cellular heterogeneity, significant batch-to-batch variability, and the challenges of large-scale manufacturing represent the principal unresolved limitations. Of particular concern, immune rejection remains a critical barrier even after the transplantation of autologous SC-islets, necessitating continued reliance on immunosuppressive therapy. Cell encapsulation and gene editing strategies have emerged as potential approaches to overcome this immunological barrier. In this review, we discuss strategies for obtaining insulin-producing cells from diverse cellular sources, summarize the latest advances in stem cell-based diabetes therapy, and propose future research directions.
The development of nonhuman primate models that replicate human systemic lupus erythematosus (SLE) remains limited. This study aimed to develop a pristane-induced SLE model in Macaca fascicularis and evaluate its capacity to mimic human-like clinical and laboratory immunological alterations.
An experimental, single-arm investigation was performed using six female M. fascicularis (2-3 years old, 3-4 kg), which received a single intraperitoneal pristane injection (5 mL/kg body weight) to induce SLE and were monitored biweekly.
Throughout the 24-week study period, all macaques developed hallmark SLE-like changes without requiring a booster, including a pronounced increase in antinuclear antibody titers (p = 0.002), with anti-dsDNA positivity detected at the study endpoint. Significant decline was observed in hemoglobin, leukocyte, and lymphocyte count (p < 0.05), reflecting hematologic perturbations consistent with human SLE. Physiologic deterioration, manifested as hyperthermia and weight loss, also emerged early (p = 0.001). Biochemical assessment demonstrated mild hepatic and renal dysfunction marked by elevated serum glutamic pyruvic transaminase (SGPT) and urea concentrations (p < 0.05). Uniform proteinuria further indicated renal involvement, although the absence of hematuria suggests a spectrum of renal injury that may be less severe than that observed in advanced human SLE and may require longer observation.
Overall, the reproducibility of autoantibody elevation and multisystem involvement demonstrates the model's translational potential. This nonhuman primate model offers a significant framework for investigating SLE pathogenesis and assessing novel therapy approaches.
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