Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Background Osteoporosis (OP) is a systemic bone disease characterized by damage to bone strength, leading to increased bone fragility and fracture risk. Cadherin 19 (CDH19) is located on chromosomes 18q22-q23, and 18q deletion is associated with terminal deletion diseases, including foot/hand deformities. However, the role of CDH19 in bone remains undefined. Methods A conditional knockout mouse model of the CDH19 gene was constructed using the Cre-loxP system, and the bone mass and bone morphology in mice were investigated using microCT and histological staining. Osteoblasts were isolated and cultured from wild-type and CDH19 knockout mice. Cell proliferation and differentiation were explored through EdU labeling, qPCR, alkaline phosphatase (ALP)/ alizarin red S (ARS) staining, and Western blot assays. The expression of genes altered in CDH19 gene knockout osteoblast was checked by RNA sequencing (RNA-seq), and subsequently confirmed by immunofluorescence and Western blot. Results We found that CDH19 could maintain the normal proliferation and differentiation in osteoblasts. After knocking out the CDH19 gene, the abilities of proliferation and osteogenesis were significantly inhibited in osteoblasts. Moreover, the bone mass of CDH19 knockout mice was significantly reduced, characterized by decreases in bone density, trabecular number, and bone volume fraction. The RNAseq analysis and western blot showed the PI3K/AKT signaling pathway was significantly inhibited in osteoblasts with CDH19 deletion. Furthermore, we demonstrated that administration of PI3K/AKT signaling pathway agonist 740Y-P partially alleviated the inhibition of osteogenic differentiation caused by CDH19 deletion in vitro and in vivo. Conclusion This study demonstrated that CDH19 regulated osteogenic differentiation by modulating the PI3K/AKT signaling pathway in osteoblasts. CDH19 may become a novel target for the treatment of bone diseases.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT), which involves supplementing oocytes with exogenous mitochondria, has been proposed as a novel strategy to improve ART outcomes. However, both its clinical efficacy and safety remain unclear.
Methods In this single-center trial, 151 patients with a history of ≥ 2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cells (BMSCs) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was the rate of day-3 good-quality embryos.
Results MIT significantly accelerated early embryonic cleavage at the 3-cell stage and 5-cell stage, but this morphokinetic alteration did not translate into improvements in good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with all offspring exhibiting normal growth and development. Exploratory analysis revealed that oocytes yielding ≥ 70% transferable embryos after MIT harbored an elevated higher burden of medium frequency (0.05–0.5) mtDNA point mutations.
Conclusions While autologous BMSCs-MIT transiently alters early cleavage kinetics, it does not demonstrate a clinical advantage in unselected patients with recurrent ART failure. Nevertheless, its observed safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker provide a foundation for shifting future MIT research from a universal approach toward precision application in molecularly stratified populations.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04475-3
Background: Mitochondrial DNA (mtDNA) deletion and oxidative stress are key contributors to skin photoaging. Mitophagy helps mitigate oxidative stress. Human adipose-derived stem cell exosomes (hADSC-Exos) have been shown to counteract skin photoaging. This study aimed to explore the role and mechanism of hADSC-Exos in addressing skin photoaging. Methods: hADSC-Exos were isolated, and their surface markers were identified. Human dermal fibroblasts (HDFs) and nude mice were exposed to ultraviolet-B (UVB) irradiation, and treated with hADSC-Exos. Oxidative stress and photoaging were assessed through SA-β-gal staining, p21 expression, mtDNA deletion, reactive oxygen species (ROS) levels, and histological analysis. The PINK1, Parkin, LC3b, and p62 protein levels were measured to evaluate mitophagy. The PINK1 small-interfering RNA (siPINK1) was then used in HDFs to investigate the role of hADSC-Exos in mitophagy. Results: In UVB-exposed HDFs and nude mice, the number of SA-β-gal-positive cells, along with levels of p21, ROS, and mtDNA deletion, were significantly increased, but these effects were reduced by hADSC-Exos. Moreover, hADSC-Exos treatment significantly elevated PINK1 and Parkin levels, as well as the LC3bII/I ratio, while reducing p62 expression. In photoaged HDFs treated with hADSC-Exos, PINK1 knockout using siRNA decreased the LC3bII/I ratio and levels of PINK1 and Parkin, while increasing p62, ROS, and mtDNA deletion compared to the negative control (NC) group. Conclusion: hADSC-Exos can mitigate skin photoaging by promoting PINK1/Parkin-mediated mitophagy, thereby reducing mtDNA deletion and oxidative stress.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025130
Tumor radioresistance and severe toxicity make reirradiation for recurrent nasopharyngeal carcinoma (NPC) a significant clinical challenge. This study aims to investigate the ability of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib to sensitize recurrent NPC cells irradiated with photon or carbon ion (C-ion), and to explore the underlying mechanism of the synergistic promotion of cell death by olaparib and ionizing radiation. The results show that olaparib has significant X-ray and C-ion radiosensitization effects on recurrent NPC cells and the associated HK-RR photon-resistant model. Radiation, particularly C-ion exposure, induces a homologous recombination (HR)-deficient gene signature in HR-proficient NPC cells, potentially increasing their sensitivity to PARP inhibition. C-ion and X-ray irradiation induces similar modes of cell death, and multiple cell death pathways [including apoptosis, necrosis, ferroptosis, senescence, and autophagic cell death (ACD)] contribute to the cytotoxic effects of radiation combined with olaparib, with ACD being the dominant pathway. Both the pharmacological and genetic inhibition of autophagy significantly attenuate the radiosensitization effect of olaparib. In conclusion, olaparib effectively sensitizes recurrent NPC cells to both X-ray irradiation and C-ion irradiation, with autophagy playing a central role in mediating this effect.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025203
Immunotherapy, including cellular therapy, has emerged as a crucial pillar in cancer treatment, complementing established modalities such as surgery, chemotherapy and radiotherapy. The clinical observation that immunotherapy is effective in only a limited proportion of patients inspires mechanistic research on the complicated regulatory network within the tumor microenvironment (TME). Circadian regulation significantly affects immune cell behavior, including the activity of immune cells and cytokine production, and emerging evidence suggests the key role of circadian regulation in the TME, which subsequently affects the effectiveness of immunotherapy. Results from preclinical and clinical studies indicate that appropriate timing of adoptive cellular therapy and immune checkpoint blockade therapy improves their efficacy. Therefore, understanding the molecular mechanism of the circadian rhythm together with its role in immunotherapy is essential for optimizing cellular function, proliferation and persistence in the TME. Here, we review how circadian rhythms influence immunotherapy and the TME across different stages of tumor progression. Future clinical protocols may integrate concepts of circadian rhythm and immunotherapy to enhance treatment response.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024090
MicroRNAs (miRNAs) are implicated in the development of cancers and may serve as potential targets for therapy. However, the functions and underlying mechanisms of miRNAs in cancers are not well understood. This work aims to study the role of miR-373-3p in colon cancer cells. We find that the expression of miR-373-3p mimics promotes and the miR-373-3p inhibitor suppresses aerobic glycolysis and proliferation of colon cancer cells. Mechanistically, miR-373-3p inhibits the expression of MFN2, a gene that is known to suppress glycolysis, which leads to the activation of glycolysis and eventually the proliferation of cells. In a nude mouse tumor model, the expression of miR-373-3p in colon cancer cells promotes tumor growth by enhancing lactate formation, which is inhibited by the co-expression of MFN2 in the cells. Administration of the miR-373-3p antagomir blunts in vivo tumor growth by decreasing lactate production. In addition, in human colon cancers, the expression levels of miR-373-3p are increased, while those of MFN2 mRNA are decreased, and the increase of miR-373-3p is associated with the decrease of MFN2 mRNA. Our results reveal a previously unknown function and underlying mechanism of miR-373-3p in the regulation of glycolysis and proliferation in cancer cells and underscore the potential of targeting miR-373-3p for colon cancer treatment.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
This review delves into the crosstalk network between oligodendrocytes and other glial cells in the context of demyelinating diseases. Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS), are crucial for maintaining the function and integrity of axons and myelin sheaths. In demyelination pathologies, various factors hinder the normal differentiation of oligodendrocyte precursor cells, obstructing the myelin regeneration process, which is a primary barrier to therapeutic myelin repair. Emerging evidence highlights the critical role of glial cell interactions in CNS homeostasis and myelin regeneration, increasing interest in the treatment of demyelinating diseases. This article reviews the role of interactions between oligodendrocytes and other CNS glial cells in demyelinating and neurological diseases. Previous findings suggest that other CNS glial cells influence the survival and metabolic activity of oligodendrocytes through cell interactions, significantly affecting myelin formation and impacting demyelinating diseases characterized by myelin regeneration disorders. Targeted modulation of oligodendrocytes and their interactions with other cells at specific temporal stages may indicate a novel therapeutic direction for demyelinating diseases and offer fresh perspectives on the study of mechanisms and therapeutic approaches for related neurological conditions.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025126
Arrhythmias, especially ventricular arrhythmias (VAs), are the primary cause of mortality following myocardial infarction (MI) and are typically attributable to electrophysiological disorders of the heart. Our previous work demonstrated that CDR1as knockdown ameliorates arrhythmias by modulating Nav1.5 and Kir6.2 channels post-MI. This study aims to explore the role of CDR1as in calcium channel remodeling subsequent to ischemic arrhythmia. We employ MI in mice by ligating the left anterior descending coronary artery (LAD) and use patch-clamp techniques to measure the Ca current (ICaL) in isolated ventricular cardiomyocytes. The results show that the expression of Cav1.2 is significantly decreased in the infarct border zone at 12 h post-MI. CDR1as knockdown via AAV9-CDR1as-shRNA administration leads to an enhancement of cardiac function and a restoration of both ICaL density and Cav1.2 expression in MI model mice. These findings indicate that targeting the CDR1as pathway to modulate calcium channels can be a viable strategy for antiarrhythmic therapy following MI.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024161
Acute lung injury (ALI) is a severe pulmonary disorder of sepsis with high clinical incidence and mortality. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-cysteinyl aspartate specific proteinase 1-gasdermin D (GSDMD)-dependent pyroptosis of alveolar epithelial cells (AECs) has emerged as a crucial contributor to ALI during sepsis. Phillyrin (PHI), a natural lignan isolated from the traditional Chinese herbal medicine Forsythia suspensa, has been shown to have anti-inflammatory, antioxidant and antiviral properties. However, little is known about the protective role and potential mechanism of PHI in sepsis-induced ALI, and it is uncertain whether the protective effect of PHI in sepsis-induced ALI is connected to pyroptosis. This study aims to examine the preventive effects of PHI on sepsis-induced ALI via the inhibition of NLRP3/caspase-1/GSDMD-mediated pyroptosis in AECs. Our findings demonstrate that preadministration of PHI successfully reduces sepsis-induced pulmonary edema, systemic/pulmonary inflammation, and pulmonary histological damage in lung tissues, bronchoalveolar lavage fluid, and the serum of septic mice. Intriguingly, PHI preadministration suppresses sepsis-induced protein expressions of pyroptosis-specific markers, especially their active forms. In vitro assays show that PHI pretreatment also protects type II AECs (MLE-12) from lipopolysaccharide-induced pyroptosis by preventing the activation of the pyroptosis signaling pathway. The results from molecular docking and surface plasmon resonance reveal that PHI has a significant affinity for direct binding to the GSDMD protein, suggesting that GSDMD is a potential pharmacological target for PHI. In conclusion, PHI can prevent sepsis-triggered ALI by effectively suppressing the activation of the canonical pyroptosis signaling pathway and pyroptosis of AECs.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025147
CD47, a cell surface transmembrane glycoprotein, is an innate immune checkpoint that suppresses phagocytic clearance. Emerging evidence suggests that CD47 has noncanonical functions. However, its involvement in chemotherapy resistance is not well understood. Our study reveals that cisplatin treatment upregulates CD47 expression across multiple cancer cell lines. Cisplatin induces the expression of CD47 through the ATM/NF-κB signaling pathway. Genetic ablation of CD47 dramatically sensitizes cancer cells to cisplatin. Mechanistically, CD47 depletion potentiates cisplatin-induced DNA damage, as demonstrated by elevated γH2AX formation and ATM phosphorylation. Knockdown of CD47 inhibits the expression of DNA repair genes ERCC1, FANCA, and BRCA2 through the ATM/NF-κB pathway. Remarkably, CD47 blockade with neutralizing antibodies recapitulates these effects, synergistically potentiating cisplatin’s DNA-damaging capacity while suppressing DNA repair capacity. CD47 blockade also potentiates cisplatin’s tumor inhibitory effect in vivo. These findings establish a novel mechanism whereby CD47 promotes cisplatin resistance through transcriptional regulation of DNA repair pathway, providing rationale for combining CD47-targeted therapies with conventional chemotherapy. This dual approach could simultaneously overcome immune evasion while enhancing treatment efficacy.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024138
Chemoresistance is the primary reason for poor prognosis in patients with pancreatic cancer (PC). Recent studies have indicated that ferroptosis may improve chemoresistance, but the underlying mechanisms remain unclear. In this study, significant upregulation of heat shock protein 90α (Hsp90α) expression is detected in the peripheral blood and tissue samples of patients with chemoresistant PC. Further studies reveal that Hsp90α promotes the proliferation, migration, and invasion of a chemoresistant pancreatic cell line (Panc-1-gem) by suppressing ferroptosis. Hsp90α competitively binds to Kelch-like ECH-associated protein 1 (Keap1), liberating nuclear factor erythroid 2-related factor 2 (Nrf2) from Keap1 sequestration. Nrf2 subsequently translocates into the nucleus and activates the glutathione peroxidase 4 (GPX4) pathway, thereby suppressing ferroptosis. This process further worsens the chemoresistance of PC cells. This study provides valuable insight into potential molecular targets to overcome chemoresistance in PC. It sheds light on the intricate mechanisms linking Hsp90α and ferroptosis to chemoresistance in PC and provides a theoretical foundation for the development of novel therapeutic strategies.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05061-x
Osteoporosis is characterized by impaired bone formation relative to resorption, yet the molecular drivers of osteoblast dysfunction remain incompletely defined. Cadherin 19 (CDH19), located at chromosome 18q22-q23, has been linked to 18q deletion syndromes presenting with skeletal deformities, but its role in bone homeostasis was previously unknown. Using a Cre-loxP conditional knockout model, we demonstrate that CDH19 deletion in mice significantly reduces bone mass, with decreases in bone density, trabecular number, and bone volume fraction. Osteoblasts isolated from CDH19 knockout mice exhibit suppressed proliferation and osteogenic differentiation, as evidenced by EdU labeling, qPCR, alkaline phosphatase and alizarin red S staining, and Western blot. RNA sequencing and subsequent immunofluorescence and Western blot analyses reveal that the PI3K/AKT signaling pathway is markedly inhibited in CDH19-deficient osteoblasts. Administration of the PI3K/AKT agonist 740Y-P partially rescues the osteogenic differentiation deficit both in vitro and in vivo. These findings establish CDH19 as a critical regulator of osteoblast function through PI3K/AKT signaling and identify it as a potential therapeutic target for bone diseases such as osteoporosis.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05059-5
Background: Mitochondrial dysfunction contributes to poor embryo quality and recurrent assisted reproductive technology (ART) failure. Mitochondrial transplantation (MIT) has been proposed to improve ART outcomes, but its efficacy and safety remain unclear. Methods: In this single-center trial, 151 patients with ≥2 failed ART cycles provided 1178 metaphase II (MII) oocytes. Sibling oocytes were randomized 1:1 to receive autologous bone marrow mesenchymal stem cell (BMSC) mitochondria co-injection during intracytoplasmic sperm injection (ICSI) or standard ICSI. The primary outcome was day-3 good-quality embryo rate. Results: MIT significantly accelerated early cleavage at the 3-cell and 5-cell stages, but this did not translate into improved good-quality embryo rate, clinical pregnancy rate, or live birth rate. Long-term follow-up of 23 live births revealed no adverse effects, with normal growth and development. Exploratory analysis showed that oocytes yielding ≥70% transferable embryos after MIT harbored a higher burden of medium-frequency (0.05–0.5) mtDNA point mutations. Conclusions: Autologous BMSC-MIT transiently alters early cleavage kinetics but does not demonstrate clinical advantage in unselected patients with recurrent ART failure. Its safety profile and the identification of mtDNA mutation burden as a potential predictive biomarker support shifting future research toward precision application in molecularly stratified populations.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21266
BACKGROUND: Shear-wave elastography is valuable for rehabilitation diagnosis and treatment, but it has not been sufficiently promoted in clinical practice. OBJECTIVE: To explore the trends and hotspots of ultrasound shear wave elastography in skeletal muscle research by visualizing and analyzing the international literature from the past 10 years, thereby providing a reference for clinical diagnosis and follow-up research. METHODS: Based on the Web of Science Core Collection database (2015-2024), the number of publications, countries/regions, institutions, authors, journals, cited literature, and key words from the 978 included articles were visualized and analyzed using CiteSpace software. RESULTS AND CONCLUSION: (1) With a 16.2% average annual growth in global publications, China has the highest number of publications worldwide (197), but its international collaborative network is relatively weak. The University of Nantes in France has the highest number of publications (50), and the University of Queensland has the most influential collaborative network. (2) Ultrasound in Medicine and Biology is the journal with the most publications (33). Noriaki Ichihashi is the most prolific author. (3) The gastrocnemius muscle is one of the most frequently examined sites. Shear wave elastography shows significant clinical potential in central nervous system diseases and sports injuries. (4) The research focus has shifted from basic biomechanics to dynamic clinical assessment and therapeutic interventions. (5) Future diagnostic techniques should be more standardized and refined, establishing normative data ranges for muscle tissue, while considering individual biological variability in elasticity values.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21428
OBJECTIVE: In recent years, many scholars have applied 3D-printed artificial vertebrae to anterior cervical vertebral subtotal vertebral resection and bone grafting fusion, but whether it is more effective than traditional titanium cages remains controversial. This study aims to systematically evaluate the effectiveness and safety of 3D-printed artificial vertebrae compared with traditional titanium cages as implants for anterior cervical corpectomy and fusion in the treatment of spondylosis. METHODS: Databases such as CNKI, WangFang, CBM, VIP, PubMed, EMBASE, and The Cochrane Library were searched to collect the clinical research on the application of 3D-printed artificial vertebrae in anterior cervical corpectomy and fusion from the establishment of each database to February 2025. After screening the literature, extracting the data and evaluating the methodological quality of the included studies, the meta-analysis was performed using Rev Man 5.4 software. RESULTS: A total of 10 studies were included, comprising 2 prospective randomized controlled studies, 6 retrospective cohort studies, and 2 prospective cohort studies, all of high quality. The included studies involved 534 patients, with 273 in the 3D-printed group and 261 in the control group. Meta-analysis results showed that the 3D-printed group was superior to the control group in terms of operation time [SMD=-1.13, 95%CI(-1.87, -0.39), P=0.003], loss of intervertebral disc height at last follow-up [SMD=-3.01, 95%CI(-5.74, -0.29), P=0.03], neck disability index at 3 months postoperatively [SMD=-0.34, 95%CI(-0.66, -0.03), P=0.03], prosthesis subsidence rate [OR=0.19, 95%CI(0.11, 0.32), P < 0.000 01], and postoperative dysphagia incidence [OR=0.43, 95%CI(0.21, 0.90), P=0.03], with significant differences. There were no significant differences in blood loss, hospital stay, postoperative Japanese Orthopaedic Association score, postoperative visual analogue scale score, postoperative neck disability index (at 6 months and last follow-up), and fusion rate between the two groups (P > 0.05). CONCLUSION: Compared with traditional titanium cages, 3D-printed artificial vertebral bodies have significant advantages in improving surgical efficiency, maintaining postoperative intervertebral disc height, reducing postoperative dysphagia incidence, and reducing prosthesis subsidence rate.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21343
BACKGROUND: The occurrence of diabetic encephalopathy may be closely related to neuronal aging, but its underlying molecular mechanism is not fully understood. Therefore, exploring the role of neuronal senescence in diabetic encephalopathy is of great significance for further revealing the pathogenesis of diabetic encephalopathy. OBJECTIVE: To investigate the effect and mechanism of emodin on senescence of HT-22 cells under high glucose conditions. METHODS: HT-22 cells were divided into control group (glucose concentration 25 mmol/L), high glucose group (glucose concentration 55 mmol/L), and high glucose + emodin group (glucose concentration 55 mmol/L, emodin concentration 100 µmol/L) and cultured for 48 h. The growth state of cells in each group was observed under microscope; CCK-8 assay was used to detect cell viability; ELISA was used to detect telomerase reverse transcriptase activity; RT-qPCR and western blot were used to detect the expression of senescence-related proteins P53, P21, and P16; immunofluorescence, RT-qPCR and western blot were used to detect the expression of lamin A/C. RESULTS AND CONCLUSION: Compared with the control group, the high glucose group showed obvious growth inhibition under microscope, characterized by decreased cell number, increased cell volume, and flattened morphology; compared with the high glucose group, the high glucose + emodin group showed significantly increased cell number and more regular morphology. Compared with the control group, cell viability was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, cell viability was significantly increased in the high glucose + emodin group (P < 0.0001). Compared with the control group, telomerase reverse transcriptase activity was significantly decreased in the high glucose group (P < 0.001). Compared with the control group, the expression levels of P53, P21, and P16 were significantly increased in the high glucose group (P < 0.05); compared with the high glucose group, the expression levels of P53, P21, and P16 were significantly decreased in the high glucose + emodin group (P < 0.05). Compared with the control group, the expression level of lamin A/C was significantly decreased in the high glucose group (P < 0.0001); compared with the high glucose group, the expression level of lamin A/C was significantly increased in the high glucose + emodin group (P < 0.05). The results indicate that emodin may slow down the senescence of HT-22 cells induced by high glucose by upregulating the expression of lamin A/C.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21451
BACKGROUND: Hydrogel materials have garnered significant attention in tissue repair due to their good biocompatibility and degradability, but single hydrogels lack antibacterial and osteogenic functions, limiting clinical application. OBJECTIVE: To prepare hydrogels with both antibacterial and osteogenic functions for bone tissue repair. METHODS: Copper and zinc co-doped hydroxyapatite (Cu/Zn HA) was synthesized by chemical precipitation. Cu/Zn HA, epigallocatechin gallate (EGCG), and Cu/Zn HA+EGCG were separately added to photoinitiators, and methacrylated gelatin (GelMA) was added to the photoinitiator solutions. After UV irradiation at 405 nm for 20 s, four hydrogels were prepared: GelMA (G), Cu/Zn HA/GelMA (G-Cu/Zn HA), EGCG-modified GelMA (G-E), and EGCG-modified Cu/Zn HA/GelMA (G-E-Cu/Zn HA). The microstructure, compressive mechanical properties, swelling, degradation, and release kinetics of metal ions and EGCG were characterized. Antibacterial properties were evaluated against Staphylococcus aureus and Escherichia coli using agar plate coating, live/dead staining, and scanning electron microscopy. Cytocompatibility was assessed with MC3T3-E1 cells via live/dead staining and CCK-8 assay. Osteogenic activity was evaluated after osteogenic induction using alkaline phosphatase staining, alizarin red S staining, and osteogenic-related gene expression. RESULTS AND CONCLUSION: Scanning electron microscopy showed porous internal structures in all hydrogels, with G and G-E having relatively smooth surfaces, while G-Cu/Zn HA and G-E-Cu/Zn HA had increased surface roughness. Compressive stresses were 10.48, 12.91, 23.64, and 41.03 kPa for G, G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA, respectively. Compared with G, the swelling time and equilibrium swelling ratio decreased in G-E, G-Cu/Zn HA, and G-E-Cu/Zn HA. G-E-Cu/Zn HA exhibited prolonged degradation. G-Cu/Zn HA and G-E-Cu/Zn HA released Cu2+, Zn2+, and Ca2+ over 30 days, with G-Cu/Zn HA releasing more Cu2+ and Zn2+ than G-E-Cu/Zn HA. G-E-Cu/Zn HA significantly inhibited the burst release of EGCG compared with G-E. Antibacterial assays showed that all modified hydrogels inhibited bacteria, with G-E-Cu/Zn HA showing the strongest effect. All hydrogels were cytocompatible. Osteogenic assays showed that G had the weakest osteogenic ability, while G-E-Cu/Zn HA had the strongest. CONCLUSION: The EGCG-modified Cu/Zn HA/GelMA composite hydrogel exhibits excellent antibacterial and osteogenic properties.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21533
BACKGROUND: Previous studies have confirmed that the "metabolic memory" effect induced by a sustained high-glucose environment can significantly exacerbate damage in mouse hippocampal neuronal cell lines HT-22. OBJECTIVE: To investigate the effects of glycemic variability and sustained high glucose on apoptosis and the expression of histone deacetylase 4 (HDAC4) and silent information regulator 1 (SIRT1) in mouse hippocampal neuronal HT-22 cells. METHODS: Passage 6 HT-22 cells were cultured in three groups after adherence: control group (25 mmol/L glucose for 3 or 5 days), high glucose group (55 mmol/L glucose for 3 or 5 days), and glycemic variability group (alternating 25 mmol/L and 55 mmol/L glucose every 12 hours for 3 or 5 days). After 3 days of culture, cell morphology was observed under an optical microscope. After 5 days, apoptosis was detected by flow cytometry. Cell viability was measured by CCK-8 assay at 3, 4, and 5 days. Reactive oxygen species (ROS) levels were detected using 2,7-dichlorofluorescein diacetate fluorescent probe at 3 and 5 days. Histone deacetylase (HDAC) content in the supernatant was measured by ELISA. Protein expression of Bax, Bcl-2, Caspase-3, Cleaved Caspase-3, SIRT1, and HDAC4 was detected by western blot, and mRNA expression of Bax, Bcl-2, Caspase-3, SIRT1, and HDAC4 was detected by RT-qPCR. RESULTS AND CONCLUSION: (1) Under the optical microscope, control cells grew well, forming a dense network with interconnected synapses; high glucose and glycemic variability groups showed inhibited growth and reduced synaptic connections. Apoptosis rate was higher in the high glucose group than in the control and glycemic variability groups (P < 0.05), and higher in the glycemic variability group than in the control group (P < 0.05). (2) At 3, 4, and 5 days, cell viability was lower in the high glucose group than in the control and glycemic variability groups (P < 0.05), and lower in the glycemic variability group than in the control group (P < 0.05). (3) At 3 and 5 days, ROS levels were higher in the high glucose group than in the control and glycemic variability groups (P < 0.05), and higher in the glycemic variability group than in the control group (P < 0.05). HDAC content in the supernatant was higher in the high glucose and glycemic variability groups than in the control group (P < 0.05). (4) At 3 and 5 days, protein and mRNA expression of HDAC4, Bax, and Caspase-3 were higher in the high glucose and glycemic variability groups than in the control group (P < 0.05), while SIRT1 and Bcl-2 expression were lower (P < 0.05). Cleaved Caspase-3 protein expression was higher in the high glucose and glycemic variability groups than in the control group (P < 0.05). (5) These results indicate that glycemic variability may induce apoptosis in HT-22 cells by upregulating HDAC4 expression and downregulating SIRT1 expression.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21546
BACKGROUND: Articular cartilage is primarily composed of collagen. Using collagen as a scaffold material, combined with autologous bone marrow mesenchymal stem cells for in situ repair, has become a new method for treating articular cartilage damage.
OBJECTIVE: To evaluate the effectiveness of collagen combined with fibrin sealant in repairing articular cartilage defects in rabbits.
METHODS: Forty-eight New Zealand rabbits were used. Full-thickness cartilage defects of 4.5 mm in diameter and 3 mm in depth were created on the trochlear surface of the medial femoral condyle of the left hind limbs. The rabbits were randomly divided into four groups: microfracture group (n=12) underwent microfracture surgery. Collagen group (n=12) underwent microfracture surgery followed by injection of domestically produced collagen into the cartilage defect. CartiRegen group (n=12) underwent microfracture surgery followed by injection of a mixture of imported collagen and fibrin sealant into the cartilage defect. Experimental group (n=12) underwent microfracture surgery followed by injection of a mixture of domestically produced collagen and fibrin sealant into the cartilage defect. At 12 and 24 weeks post-surgery, knee joint MRI examinations were performed, and the knee joint cartilage repair tissue was subjected to hematoxylin-eosin, toluidine blue, safranin O-fast green staining, type II collagen immunohistochemical staining, ICRS scoring, and Mankin scoring. The compression modulus and hardness of the repaired cartilage were measured at 24 weeks.
RESULTS AND CONCLUSION: MRI examination showed that at 24 weeks, the microfracture group had almost complete filling of the cartilage defect, but poor integration with surrounding normal cartilage; the collagen group had almost complete filling and basically complete integration with slight differences; the CartiRegen and experimental groups had complete filling and no obvious differences in integration and surface with surrounding healthy cartilage. Histological staining showed that the microfracture group had light and uneven staining with poor cartilage morphology; the collagen group had relatively uniform staining, smooth repair surface, basically integrated with surrounding normal cartilage, but with fissures; the CartiRegen and experimental groups had uniform staining, smooth surface, dense tissue, good integration with surrounding tissue, and good filling. The ICRS and Mankin scores at 24 weeks were lower in the CartiRegen and experimental groups than in the microfracture and collagen groups (P < 0.05). The hardness of the repaired cartilage at 24 weeks was greater in the collagen, CartiRegen, and experimental groups than in the microfracture group (P < 0.05). These results indicate that collagen combined with fibrin sealant and microfracture has good repair effects on cartilage damage.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025105
Demyelinating diseases of the central nervous system (CNS) are characterized by failed remyelination, largely due to arrested oligodendrocyte precursor cell (OPC) differentiation. This review synthesizes evidence on the crosstalk between oligodendrocytes (OLGs) and other glial cells—astrocytes, microglia, and neurons—in the context of demyelination. OLGs, the myelin-forming cells of the CNS, are essential for axonal integrity and saltatory conduction. Under pathological conditions, factors including astrocyte-derived PDGF and leukemia inhibitory factor (LIF), microglial polarization states, and neuronal activity modulate OLG survival, metabolic support, and process outgrowth. Astrocytes promote process outgrowth via basic fibroblast growth factor (bFGF) and extracellular matrix interactions, while also regulating iron metabolism and exosomal secretion from OPCs through integrin β4-mediated adhesion. Microglial heterogeneity, with M1/M2 polarization, influences neuroinflammation and remyelination outcomes. The review highlights that astrocyte activation via STAT3 signaling determines the balance between oligodendrocyte and Schwann cell remyelination. These intercellular interactions significantly impact myelin regeneration and offer potential therapeutic targets. Modulating these interactions at specific temporal stages may provide novel strategies for treating demyelinating diseases and related neurological conditions. The integration of single-cell resolution data on microglial heterogeneity and spatial-temporal dynamics is critical for developing targeted interventions.