Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05073-7
Exosomes have emerged as critical mediators of intercellular and inter-organ communication in bone biology. Secreted by bone-resident cells such as osteoblasts, osteoclasts, osteocytes, and mesenchymal stem cells (MSCs), these nanosized vesicles carry diverse molecular cargos that regulate bone remodeling, regeneration, and skeletal homeostasis. In addition to mediating local communication within the bone microenvironment, exosomes also participate in systemic crosstalk communication between bone and other tissues, including skeletal muscle, adipose tissue, gut microbiota, the immune system, the nervous system, and vasculature. Disruption of these exosome-mediated pathways contributes to the development and progression of bone diseases, including osteoporosis, osteoarthritis, osteonecrosis of the femoral head, and bone metastases. This review summarizes current advances in exosome-mediated signaling in both physiological and pathological contexts, with particular emphasis on their roles as biomarkers, therapeutic agents, and drug delivery vehicles. We also discuss the emerging contribution of artificial intelligence (AI) to exosome research, especially in biomarker discovery, disease classification, and target identification, as well as the major challenges that currently limit clinical translation. Together, these insights highlight the potential of exosome-based strategies for precision medicine in bone diseases.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04417-z
Background Urothelial regeneration is a crucial part of bladder tissue engineering. However, there is a lack of ideal “seed cells” in current practices. Here, we demonstrated that a sub-population of p63 positive basal cells could be activated and differentiate into intermediate and superficial umbrella cells after full-thickness mucosal resection in rabbit.
Methods A focal mucosal resection model was used to characterize the role of different urothelial cells during regeneration. Urothelial basal cells were isolated from rabbit bladder mucosa and cultured in vitro. The basal cells were then transplanted in vivo in a manner of cell sheet for reconstruction.
Results Via single-cell RNA sequencing (scRNA-seq), it has been confirmed that the cluster of KRT5high TP63-expressing cells possesses a ‘stemness’ signature which can give rise to lineage cell types sequentially. With a strong support from the underneath pre-set capsule vascular bed, the transplanted cell sheet could develop into a physio-morphology resembled to the native mucosa in vivo. Importantly, we validated that the bioengineered urothelium implemented perfect barrier function after implanted to bladder.
Conclusions In summary, bioengineering urothelium with KRT5high TP63-expressing basal cells on a capsule vascular bed offers a promising strategy for bladder tissue engineering and provides a model for drug screening and bladder disease research.
Stem Cell Research & Therapy•2025•DOI: 10.1186/s13287-025-04241-5
Background Chronic diabetic wounds pose a significant clinical challenge due to the limited efficacy of current treatments. This study aimed to investigate the role and potential mechanisms of adipose-derived mesenchymal stem cells (ADSCs) overexpressing acidic fibroblast growth factor (aFGF) in diabetic wound healing in a rat model. Methods ADSCs were genetically modified to achieve stable overexpression of aFGF. Varying doses of aFGF-ADSCs (1×10⁶, 2×10⁶, 3×10⁶, 4×10⁶) were injected into the muscular tissue surrounding diabetic rat wounds. We assessed aFGF expression and its impact on various stages of wound healing, including angiogenesis, inflammatory response, epithelialization, and collagen deposition. Transcriptomic sequencing was performed to explore the underlying mechanisms driving enhanced wound healing. Results Lentiviral transduction successfully induced stable aFGF overexpression in ADSCs. In vivo experiments revealed that varying doses of aFGF-ADSCs markedly enhanced wound healing in diabetic rats in a dose-dependent manner. The dose of 3×10⁶ aFGF-ADSCs demonstrated the most significant effect. In the 3×10⁶ aFGF-ADSCs group, expression levels of aFGF, CD31, and CD163 were significantly higher than in other groups (p < 0.05), while CD86 expression was significantly lower (p < 0.05). Conclusion Single doses of aFGF-ADSCs comprehensively improved various aspects of wound repair in diabetic rats, offering a potential new approach for treating chronic diabetic wounds. The mechanism of action involves promoting angiogenesis, modulating inflammatory responses, accelerating epithelialization, and optimizing collagen deposition.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03945-4
Background Lung injury and pulmonary fibrosis (PF), frequently arising as sequelae of severe and acute lung disease, currently face a dearth of effective therapeutic potions. Mesenchymal stem cells (MSCs) with immunomodulatory and tissue repair functions have immense potential to treat lung injury and PF. However, the optimal route of administration, timing, and frequency of dosing remain elusive. Human embryonic stem cell-derived immunity-and-matrix-regulatory cells (IMRCs) have shown therapeutic potential for lung injury and PF. Methods To ascertain the optimal therapeutic regimen for IMRCs in PF, we conducted an experimental study. Utilizing a mouse model of PF induced by bleomycin (BLM), IMRCs were administered via either a single or double intravenous (IV) or intratracheal (IT) injection on the first and seventh days post-BLM induction. Results Our findings revealed that IV infusion of IMRCs surpassed IT infusion in enhancing survival rates, facilitating body weight recovery, and optimizing Ashcroft and Szapiel scores among the model mice. Notably, IV administration exhibited a more profound ability to mitigate lung inflammation and fibrosis. Moreover, earlier and more frequent administrations of IMRCs were found to be advantageous in enhancing their therapeutic effects. Specifically, early administration with two IV infusions significantly improved body weight, lung organ coefficient, pulmonary ventilation and diffusion functions, and PF. This was accompanied by an increase in alveolar type I and II epithelial cells and a suppression of macrophage infiltration via CD24. Conclusion Collectively, these results suggested that IMRCs infusion ameliorated lung injury by promoting lung regeneration and inhibiting macrophage infiltration in a route, time, and frequency-dependent manner.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03835-9
Background Facial infiltrating lipomatosis is characterized by excessive growth of adipose tissue. Its etiology is associated with somatic phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) variants, but the specific mechanisms are not yet fully understood. Methods We collected facial adipose tissue from both FIL patients and non-FIL individuals, isolated the stromal vascular fraction (SVF) and performed single-cell transcriptome sequencing on these samples. Results We mapped out the cellular landscape within the SVF, with a specific focus on a deeper analysis of fibro-adipogenic precursor cells (FAPs). Our analysis revealed that FAPs from FIL patients (FIL-FAPs) significantly overexpressed FK506 binding protein 51 (FKBP5) compared to FAPs from individuals without FIL. Further experiments indicated that FKBP5 is regulated by the PI3K-AKT signaling pathway. The overactivation of this pathway led to an increase in FKBP5 expression. In vitro experiments demonstrated that FKBP5 promoted adipogenic differentiation of FAPs, a process that could be hindered by FKBP5 knockdown or inhibition. Additionally, in vivo assessments confirmed FKBP5’s role in adipogenesis. Conclusions These insights into the pathogenesis of FIL underscore FKBP5 as a promising target for developing non-surgical interventions to manage the excessive adipose tissue growth in FIL.
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•2024•DOI: 10.3724/abbs.2024049
Chronic renal failure (CRF) is a severe syndrome affecting the urinary system for which there are no effective therapeutics. In this study, we investigate the effects and mechanisms of aminophylline in preventing CRF development. A rat model of chronic renal failure is established by 5/6 nephrectomy. The levels of serum creatinine (SCR), urinary protein (UPR), and blood urea nitrogen (BUN) are detected by ELISA. Histological evaluations of renal tissues are performed by H&E, Masson staining, and PAS staining. Functional protein expression is detected by western blot analysis or immunofluorescence microscopy. Glomerular cell apoptosis is determined using the TUNEL method. Results show that Aminophylline significantly reduces the levels of SCR, UPR, and BUN in the CRF model rats. Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats. The protein expression levels of nephrin, podocin, SIRT1, p-AMPK, and p-ULK1 are greatly increased, while p-mTOR protein expression is markedly decreased by aminophylline treatment. Additionally, the protein level of LC3B in CRF rats is significantly increased by aminophylline. Moreover, aminophylline alleviates apoptosis in the glomerular tissues of CRF rats. Furthermore, resveratrol promotes SIRT1, p-AMPK, and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats. Selisistat (a SIRT1 inhibitor) mitigates the changes in SIRT1, p-AMPK, p-ULK1, p-mTOR, and LC3B expressions induced by aminophylline. Finally, RAPA alleviates renal injury and apoptosis in CRF rats, and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats. Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025133
As a highly aggressive malignancy arising from melanocytes, malignant melanoma accounts for the majority of skin cancer-related deaths worldwide. Metastases, particularly lung and brain metastases, contribute significantly to mortality. Although targeted therapy (BRAF/MEK inhibitors) and immunotherapy (checkpoint inhibitors) have greatly improved the overall survival of patients, drug resistance and toxicity remain major clinical challenges. Therefore, exploring new approaches to combat melanoma metastasis is imperative. Melanoma metastasis involves multiple processes, including phenotype switching (epithelial-mesenchymal transition, EMT), migration, invasion and infiltration. Phenotype switching occurs at the early stage of metastasis and is characterized by the downregulation of epithelial markers (e.g., E-cadherin) and the upregulation of mesenchymal markers (e.g., N-cadherin and Vimentin). Metastasis depends on highly regulated and complex remodeling of the tumor microenvironment formed by cells as well as by biochemical and biophysical components of the extracellular matrix (ECM) and their intricate interactions within and around a solid tumor mass. These processes are primarily mediated by the altered expression of metastasis-associated genes, and targeting the expression of these genes may be a promising strategy for inhibiting melanoma metastasis. TMEM16A (also known as ANO1), a calcium-activated chloride channel (CaCC) localized to the plasma membrane and organelle membranes, is widely expressed in tissues such as airways, smooth muscles, and neurons, where it plays important physiological roles in regulating smooth muscle contraction and chloride ion secretion. Growing evidence indicates that TMEM16A is overexpressed in various cancers and contributes to tumor progression by increasing cell proliferation, invasion, and metastasis. The expression level of TMEM16A is closely related to tumor size and differentiation, is associated with advanced stage and poor prognosis, and can even be used as a biomarker for certain malignant tumors. We previously observed a high expression level of TMEM16A in a human melanoma cell line, A375, which harbors a BRAF V600E mutation, and demonstrated its role in promoting tumor growth. Here, we further showed that elevated TMEM16A expression contributes to melanoma metastasis.
Stem Cell Research & Therapy•2024•DOI: 10.1186/s13287-024-03780-7
Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body’s in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261507
This study reports the fabrication and in vitro evaluation of carrier-free self-assembled nanoparticles (SSD-CBD) composed of saikosaponin D (SSD) and cannabidiol (CBD) at a 3:1 mass ratio via nano co-precipitation. Assembly mechanisms were probed using XPS, FTIR, and 1H-1H NOESY, revealing hydrogen bonding and hydrophobic interactions as principal driving forces. Physicochemical characterization by TEM and DLS confirmed a stable nanoscale architecture. The formulation exhibited pH-responsive release, preferentially discharging payload in tumor microenvironment (pH 6.8) while retaining stability at physiological pH 7.4. In HepG2 hepatocellular carcinoma cells, SSD and CBD displayed synergy with a combination index (CI) of 0.79. MTT assays, Annexin V-FITC/PI flow cytometry, and caspase activity measurements demonstrated that SSD-CBD nanoparticles induce apoptosis via the mitochondrial pathway. The carrier-free strategy addresses CBD's poor aqueous solubility and instability, simultaneously improving delivery efficiency and enabling precise synergistic drug co-administration. These findings provide an experimental foundation for intelligent nanomedicine development based on SSD. However, in vivo pharmacokinetics, tissue distribution, tumor accumulation, and potential hepatotoxicity of SSD in nanoformulation remain unresolved. Future work should focus on surface engineering (e.g., PEGylation or targeting ligand modification) to enhance stability and tumor targeting, integration of immunomodulatory components, and scalable GMP-compliant manufacturing with comprehensive quality control.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.16.20261605
Property prediction of traditional Chinese medicine (TCM) molecules remains constrained by their complex ring systems and conformational flexibility. Conventional graph neural networks (GNNs) treat molecules as topological graphs, discarding bond length and angle strain information critical for accurate property estimation. This study introduces the flexibility-ring enhanced graph neural network (FRGNN), which augments the graph isomorphism network (GIN) with edge descriptors encoding bond length strain and angle strain, and incorporates multiple favorable conformations to construct multi-graph data. The model was evaluated on two TCM databases comprising 37,822 molecules across seven key molecular properties, benchmarked against three state-of-the-art (SOTA) GNN models and two basic GNN models. FRGNN achieved an average root mean square error (RMSE) reduction of 8.63% relative to the second-best model across all seven tasks. For molecules containing polycyclic and macrocyclic structures, the RMSE reduction reached 10.04%. These results demonstrate that FRGNN outperforms existing SOTA small-molecule property prediction models on TCM compounds, offering a robust computational approach for complex natural product characterization. The incorporation of flexibility and ring-specific descriptors addresses a critical gap in molecular representation learning, enabling more accurate predictions for structurally diverse TCM constituents.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05073-7
Exosomes have emerged as critical mediators of intercellular and inter-organ communication in bone biology. Secreted by bone-resident cells such as osteoblasts, osteoclasts, osteocytes, and mesenchymal stem cells (MSCs), these nanosized vesicles carry diverse molecular cargos that regulate bone remodeling, regeneration, and skeletal homeostasis. In addition to mediating local communication within the bone microenvironment, exosomes also participate in systemic crosstalk between bone and other tissues, including skeletal muscle, adipose tissue, gut microbiota, the immune system, the nervous system, and vasculature. Disruption of these exosome-mediated pathways contributes to the development and progression of bone diseases, including osteoporosis, osteoarthritis, osteonecrosis of the femoral head, and bone metastases. This review summarizes current advances in exosome-mediated signaling in both physiological and pathological contexts, with particular emphasis on their roles as biomarkers, therapeutic agents, and drug delivery vehicles. We also discuss the emerging contribution of artificial intelligence (AI) to exosome research, especially in biomarker discovery, disease classification, and target identification, as well as the major challenges that currently limit clinical translation. Together, these insights highlight the potential of exosome-based strategies for precision medicine in bone diseases.
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: 10.12307/2026.21388
BACKGROUND: The oblique pulling manipulation has good therapeutic effects on cervical spondylosis, but its biomechanical mechanism of action on intervertebral discs with different degrees of degeneration is not clear. OBJECTIVE: To explore the biomechanical mechanism of the oblique pulling manipulation on the discs with different degrees of degeneration through three-dimensional finite element model. METHODS: The motion capture system was used to measure the kinematic parameters of the key steps during the oblique pulling manipulation, and a three-dimensional finite element model of the whole cervical spine of the C5/6 mildly, moderately, and severely degenerated intervertebral discs was established. The kinematic parameters were converted into moments and loaded onto the whole cervical spine of the mildly, moderately, and severely degenerated intervertebral discs in a step-by-step manner, so as to obtain the biomechanical parameters of the stress-strain of each structure during the simulated oblique pulling manipulation. RESULTS AND CONCLUSION: (1) In the simulation of the oblique pulling manipulation to the right side, with the increase of disc degeneration, the Von-Mise stress of the annulus fibrosus gradually increased, and the stress was concentrated on the right lateral side of the annulus fibrosus; the Von-Mise stress of the nucleus pulposus decreased, and the stress was concentrated at the junction of the nucleus pulposus and annulus fibrosus; the overall displacement of the intervertebral disc decreased, the stress of the left facet joint decreased, and the Von-Mise stress of the spinal cord increased, with the stress concentrated in the upper cervical spine. (2) In the simulation of the oblique pulling manipulation to the right side, with the increase of disc degeneration, the overall strain of the C5/6 intervertebral disc, the intradiscal pressure of the nucleus pulposus, and the stress of the left nerve root decreased, while the shear force of the intervertebral disc increased, the relative distance between the left nerve root and the intervertebral disc increased, and the relative distance between the right nerve root and the intervertebral disc did not change significantly. (3) The results indicate that the cervical oblique pulling manipulation improves the biomechanical imbalance of mildly and moderately degenerated intervertebral discs by adjusting the stress of the facet joints and increasing the distance between nerve roots, but for severely degenerated intervertebral discs, it should be used with caution due to the sharp increase of annulus fibrosus stress and the risk of spinal cord compression.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21381
BACKGROUND: Currently, the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation for the treatment of cervical radiculopathy have not been systematically elucidated. OBJECTIVE: To compare the biomechanical differences between cervical rotation manipulation and cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy caused by cervical disc herniation, and to provide a basis for the rational selection of manipulation in clinical practice. METHODS: A 27-year-old Asian male patient with cervical spondylotic radiculopathy caused by left posterior cervical disc herniation compressing the nerve root was recruited. The CT scan data of the skull and cervical spine were extracted to construct a finite element model of the head and full cervical spine. After model validation, the key parameters of cervical rotation manipulation and rotation-traction manipulation were loaded into the model, and the effects of the two manipulations on the stress of intervertebral disc, facet joints, spinal cord and nerve roots, disc displacement, and intervertebral foramen volume were compared. RESULTS AND CONCLUSION: (1) In terms of Von-Mise stress, the maximum stresses of cervical rotation manipulation on the annulus fibrosus, nucleus pulposus, and facet joints were 0.903, 0.139, and 2.186 MPa, respectively, which were significantly increased by 18%, 13%, and 30% compared with rotation-traction manipulation (0.765, 0.123, 1.682 MPa); while the maximum stress on the spinal cord and nerve roots was 2.547 MPa, which was 7% lower than that of rotation-traction manipulation (2.738 MPa). (2) In terms of displacement, the maximum forward displacement of the herniated side of the intervertebral disc by cervical rotation manipulation was 1.067 mm, which was 11.1% more than that of rotation-traction manipulation (0.960 mm). (3) In terms of intervertebral foramen volume changes, both manipulations increased the volume after implementation compared with before, with rotation manipulation increasing by 15.5% and rotation-traction manipulation increasing by 19.8%, the latter being more effective in expanding the intervertebral foramen volume. (4) It is suggested that cervical rotation manipulation has advantages in promoting the forward displacement of the herniated disc, but it produces higher stress on the intervertebral disc and facet joints, which may easily cause disc damage; rotation-traction manipulation will cause slightly higher stress on the spinal cord and nerve roots, but it can more effectively expand the intervertebral foramen volume and reduce the risk of disc structural damage. In clinical treatment, the advantages and disadvantages of the two manipulations should be carefully weighed and selected based on the patient's specific condition.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21348
BACKGROUND: Platelets are important blood resources, yet in routine blood bank processes they are often filtered out along with white blood cells as medical waste. Optimizing whole blood separation processes to prepare platelet lysate products and exploring their applications in tissue engineering and regenerative medicine is of great value. OBJECTIVE: To optimize whole blood separation to prepare therapeutic-grade platelet lysate and to investigate the protective effect of platelet lysate on hypoxic injury of cardiomyocytes. METHODS: Platelets were isolated from 21 qualified whole blood units under closed blood bag and tubing conditions, and 21 platelet lysates were prepared by freeze-thawing. The mass concentration ranges of platelet-derived growth factor AA, platelet-derived growth factor BB, platelet-derived growth factor AB, vascular endothelial growth factor, epidermal growth factor, insulin-like growth factor 1, fibroblast growth factor, and transforming growth factor beta 1 in platelet lysates were measured using enzyme-linked immunosorbent assay kits. Bacterial contamination was assessed by colony culture method and mycoplasma contamination by PCR detection kit. A cardiomyocyte hypoxia model was established to evaluate the protective effect of platelet lysate on hypoxic injury. RESULTS AND CONCLUSION: (1) The mass concentration ranges of major growth factors and cytokines in platelet lysates were: platelet-derived growth factor AA 12.86-24.17 μg/L, platelet-derived growth factor BB 0.25-0.32 μg/L, platelet-derived growth factor AB 85.09-114.91 μg/L, vascular endothelial growth factor 10.57-58.37 μg/L, epidermal growth factor 0.43-0.69 μg/L, insulin-like growth factor 1 106-204.9 μg/L, fibroblast growth factor 0.03-0.06 μg/L, and transforming growth factor beta 1 124.17-192.38 μg/L. (2) Colony culture and mycoplasma detection results were negative. (3) Low volume fraction (1%) platelet lysate yielded the highest proliferation efficiency of cardiomyocytes; low volume fraction (1%) platelet lysate stimulated cardiomyocytes to produce high levels of superoxide dismutase and glutathione peroxidase to protect cardiomyocytes. This study established a method for preparing therapeutic-grade platelet lysate by optimizing the whole blood separation process, which can improve the utilization rate of blood resources. Platelet lysate has high levels of major growth factors and can significantly promote the repair of hypoxic injured cardiomyocytes.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21436
BACKGROUND: In recent years, numerous studies have confirmed a close relationship between the skeletal system and the central nervous system, making the bone-brain axis a research hotspot in interdisciplinary fields; however, no studies have yet conducted a bibliometric and visualization analysis of this field. OBJECTIVE: To comprehensively analyze the research trends, hotspots, and future development directions in the bone-brain axis field utilizing bibliometric methods, providing data support and reference for subsequent studies. METHODS: A systematic literature search was conducted in the Web of Science Core Collection database to collect studies related to bone-brain axis published between 2015 and 2024. Visualization tools such as VOSviewer and CiteSpace were employed to analyze publication trends, collaboration networks, institutional contributions, and keyword co-occurrence patterns. RESULTS AND CONCLUSION: ①A total of 7,461 publications were included, showing a significant upward trend in publication volume over the past decade (2015-2024), indicating that bone-brain axis research has become an academic hotspot with increasing attention. ②The United States and China dominated the field, with the USA publishing 2,397 papers (32.1%) and China 2,307 papers (30.9%). Harvard Medical School and Zhejiang University were the most productive and central institutions. ③Professor Wang Wei was the most prolific author, focusing on the interaction between bone marrow and neuroinflammation. ④The journal Bone published the most papers (over 800), while PLOS ONE had the highest average citations per paper (45), indicating its influence. ⑤Core keywords included 'Bone Marrow', 'Stem Cells', 'Osteoporosis', and 'Neuroinflammation', reflecting fundamental research directions. Emerging frontiers included 'Extracellular Vesicles', 'Alzheimer's Disease', 'Inflammation', and 'Oxidative Stress', highlighting the importance of inflammation and neurodegenerative diseases. ⑥Future research directions include exploring the specific mechanisms of osteogenic factors and neurotransmitters in the bone-brain axis, elucidating the molecular mechanisms of inflammation, oxidative stress, and extracellular vesicles in neurodegenerative diseases and bone metabolic disorders, and promoting the translation of basic research to clinical applications.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21545
BACKGROUND: Osteonecrosis of the femoral head is a refractory disorder characterized by osteocyte apoptosis and structural collapse of the femoral head. Its pathogenesis is closely associated with vascular injury, dysregulated bone metabolism, and aberrant mechanical stress. In recent years, animal models have served as indispensable tools for simulating pathological processes, playing an irreplaceable role in elucidating molecular mechanisms of osteonecrosis of the femoral head and evaluating novel interventions. Nevertheless, the standardization of model development and their clinical translational value require systematic investigation. OBJECTIVE: To analyze the research landscape in the field of osteonecrosis of the femoral head using bibliometric approaches, with an emphasis on evaluating the application characteristics, limitations, and future optimization directions of animal models in study design, providing a reference for advancing mechanistic understanding and therapeutic development. METHODS: Literature published between January 2015 and March 2025 was retrieved from the Web of Science Core Collection (SCI-Expanded), China National Knowledge Infrastructure (CNKI), and Wanfang databases. The search strategy for English literature was TS=(osteonecrosis of the femoral head) AND TS=(mouse OR mice OR rat OR rabbit OR dog OR swine OR pig OR sheep OR monkey OR "laboratory animal" OR "experiment animal"). For Chinese literature, the search was SU=股骨头坏死 AND SU=鼠+兔+犬+猪+羊+猴+实验动物+动物实验. CiteSpace 6.3.R1 software was used to perform visualization analysis of countries, institutions, authors, keywords, and co-cited references. Trends were summarized based on animal model classification and application characteristics. RESULTS AND CONCLUSION: (1) In English literature, China contributed over 80% of the research (458 articles). Hot topics focused on steroid-induced necrosis mechanisms (e.g., oxidative stress-autophagy axis), stem cell/tissue engineering therapies, and traditional Chinese medicine interventions. The research on animal models of osteonecrosis of the femoral head exhibited a "high output-low collaboration" characteristic. (2) In Chinese literature, the publishing institutions were mainly traditional Chinese medicine-related institutions, and traditional Chinese medicine and steroid-induced osteonecrosis of the femoral head were important research hotspots. (3) Future efforts should deepen cross-species validation platforms, multi-omics integration, and collaborative strategies for the development of Chinese and Western medicine to accelerate clinical translation.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21531
BACKGROUND: The pathogenesis of coronary heart disease is complex. A single omics approach is limited in elucidating its biological pathways, whereas multi-omics integration helps reveal molecular interaction networks across different levels, addressing the limitations of single-omics methods. OBJECTIVE: To investigate the pathological mechanisms of coronary heart disease in a mouse model using proteomics and metabolomics. METHODS: Healthy SPF-grade 8-week-old male C57BL/6 mice were randomly divided into a sham operation group and a model group. The mouse model of coronary heart disease was established by ligation of the left anterior descending coronary artery, while the sham operation group underwent threading without ligation. At 28 days post-surgery, cardiac function was assessed by echocardiography, and myocardial infarct size was evaluated by TTC staining. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to screen differentially expressed proteins and metabolites between groups, followed by integrated omics analysis. RESULTS AND CONCLUSION: Compared with the sham group, the model group exhibited reduced cardiac function, with significantly decreased left ventricular ejection fraction and left ventricular fractional shortening (P < 0.05), and significantly increased myocardial infarct size (P < 0.01). Proteomics identified 420 differentially expressed proteins, including 282 upregulated (e.g., Serum amyloid A protein, protein kinase D) and 138 downregulated (e.g., Protein YIPF5, E3 ubiquitin-protein ligase). KEGG pathway enrichment revealed involvement in ATP-dependent chromatin remodeling and renin-angiotensin system pathways. Metabolomics identified 155 differential metabolites, including 56 upregulated (e.g., Thromboxane, Tromethamine) and 99 downregulated (e.g., N-Acetyl-D-Tryptophan, D-Xylulose 5-Phosphate). KEGG analysis linked these to purine metabolism and glycerophospholipid metabolism. Integrated analysis found correlations between 26 differentially expressed proteins and 16 differential metabolites, involving proteins such as ATP1A3 and Hexokinase, and metabolites such as Cytochalasin B and Gluconasturtiin. CONCLUSION: The pathological mechanisms of coronary heart disease are closely related to disturbances in energy metabolism networks, activation of inflammatory-coagulation cascades, and dysregulation of ion homeostasis.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21593
BACKGROUND: Intervertebral disc degeneration is a core pathological mechanism of discogenic diseases, characterized by an imbalance in extracellular matrix metabolism. Tissue inhibitors of metalloproteinases, as endogenous antagonists of matrix metalloproteinases, play a crucial role in regulating extracellular matrix homeostasis, but the specific functions of subtypes, signaling pathway interactions, and epigenetic regulatory mechanisms have not been systematically clarified. OBJECTIVE: To review the expression changes, functional heterogeneity, and regulatory networks of tissue inhibitors of metalloproteinases in intervertebral disc degeneration, focusing on the molecular mechanisms and signaling pathways in oxidative stress, mechanical load, and inflammatory microenvironment, and to evaluate the translational potential of gene therapy strategies based on tissue inhibitors of metalloproteinases. METHODS: The first author searched PubMed, Web of Science, Embase, CNKI, Wanfang and other databases from inception to March 2025. Chinese search terms included '椎间盘退变，椎间盘退行性变，椎间盘退化，金属蛋白酶类组织抑制剂，信号通路', and English search terms included 'Tissue Inhibitor of Metalloproteinases, Tissue Inhibitor of Metalloproteinase, TIMPs, Intervertebral disc degeneration, Disc degeneration, Degenerative Disc Disease, Degenerative Intervertebral Discs'. Finally, 76 eligible articles were included for review. RESULTS AND CONCLUSION: (1) Subtype functions of tissue inhibitors of metalloproteinases: TIMP1 exhibits dual regulation (early protection/late depletion); TIMP2 maintains extracellular matrix homeostasis by inhibiting matrix metalloproteinase activity, and its abnormal expression can activate pro-apoptotic signaling pathways (e.g., miR-185-5p/MMP2 axis and inflammatory factor-mediated MMP/TIMP imbalance); TIMP3 exerts multi-dimensional protective effects by inhibiting matrix metalloproteinase activity, tumor necrosis factor-alpha converting enzyme/tumor necrosis factor-alpha axis, and angiogenesis; TIMP4 is regulated by miR-155-5p/fibroblast growth factor 2 and participates in extracellular matrix homeostasis. (2) Epigenetic reprogramming mechanisms: Abnormal mechanical stress degrades TIMP3 mRNA through the WTAP/YTHDF2-m6A axis, while miR-222 targets TIMP3 to synergistically accelerate extracellular matrix degradation. (3) Multi-modal therapeutic strategies: Photobiomodulation (wavelength-specific regulation of TIMP/MMP), stem cell exosomes (miR-199a/GREM1 axis), and irisin intervention can remodel matrix metabolic balance. This review summarizes the theoretical framework of 'functional network imbalance of tissue inhibitors of metalloproteinases', revealing its multi-level regulatory characteristics as a core driver of intervertebral disc degeneration, and providing a theoretical basis for developing precise therapies targeting epigenetic modifications and mechano-biological coupling interventions.
Stem Cell Research & Therapy•2026•DOI: 10.1186/s13287-026-05100-7
Background: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold therapeutic potential for spinal cord injury (SCI), yet their mechanisms remain unclear. We hypothesized that investigating in situ transcriptional reprogramming of transplanted hUC-MSCs within the spinal cord microenvironment (SCE) could identify crucial genes for SCI repair. Methods: DiD-labeled hUC-MSCs were intrathecally transplanted in rats with or without sub-acute spinal cord bilateral hemisection injury and retrieved for RNA-seq. Comparative transcriptomic analysis and functional screenings in vitro and in vivo, including heterologous synapse formation assay, transplantation of MSCs with gene overexpression or knockdown, AAV-mediated neuron-specific gene expression in SCI rats, behavioral tests, and motor evoked potentials (MEPs), identified Neuroligin 3 (Nlgn3) as a novel target. Immunoprecipitation-mass spectrometry (IP-Mass spec), cell aggregation assay, and immuno-electron microscopy revealed functional interacting partners. RT-qPCR, western blotting, immunofluorescence, and co-IP elucidated mechanisms. Results: NLGN3, a neuronal cell adhesion molecule activated by SCE in transplanted hUC-MSCs, promoted therapeutic efficacy. Neuron-specific restoration of Nlgn3 in injured spinal cord alone achieved comparable therapeutic effects. Mechanistically, Nlgn3 recruits synaptic vesicle proteins Sar1a and Hspa8 to modulate synaptic strength. Combinatorial restoration of Nlgn3 with Sar1a or Hspa8 synergistically enhanced SCI repair. Conclusions: This work unveils a novel therapeutic role for Nlgn3 in SCI, enhancing MSC transplantation efficacy and directly promoting neural circuit reconstruction.