Cell Transplantation最新文献

Cesarean section (CS) scar tissue fibrosis and decreased muscle density increase the risk of uterine rupture and placental implantation in subsequent pregnancies. Given the potent anti-fibrotic and regenerative properties of human amniotic mesenchymal stem cells (hAMSCs), this study investigated their therapeutic potential in repairing uterine scars in a rat model. A full-thickness uterine wall excision model was established to mimic CS scarring. hAMSCs were transplanted at the edge of the incision. Myometrial thickness and collagen deposition within the scar were assessed histologically using hematoxylin and eosin (H&E) and Masson's staining. Immunohistochemistry evaluated the expression of MMP8, TGF-β1, VEGFA, and α-SMA within the scar region. mRNA transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to explore possible mechanisms. A total of 110 rats were used in the study, 30 in the sham group, 40 in the phosphate-buffered saline (PBS) control group and 40 in the hAMSCs treatment group. Compared with the PBS group, the hAMSCs group exhibited a 35% reduction in collagen fiber area and a 28% increase in smooth muscle cell density (P < 0.05). The MMP8, VEGFA, and α-SAM expressions in the uterine scar area of rats increased, whereas the TGF-β1 expression decreased (P < 0.05). Transcriptome sequencing and real-time fluorescence quantitative PCR results showed that the expression levels of Wnt4, Fzd5, Wnt5a, and PPARD genes were lower in the uterine scar region of rats in the hAMSCs group compared with those in the PBS group. Transplantation of hAMSCs inhibits scar formation in uterine wounds and promotes regeneration of smooth muscle tissue and neovascularization, which in turn promotes uterine wound repair. This effect may be related to the activation of Wnt pathway and the inhibition of PPARD gene expression.

Organoids, which are three-dimensional cultures derived from pluripotent or adult stem cells, meticulously mimic human organ architecture and function, revolutionizing biomedical research. Patient-derived organoids have emerged as powerful tools in disease modeling, particularly in cancer research. For instance, in the case of colorectal cancer, organoids are developed from tumor tissues of patients, allowing for drug sensitivity tests that can inform personalized treatment plans, as seen in the case of a patient responding well to specific chemotherapy drugs. In addition, organoids have been used to study regenerative mechanisms, such as the repair of intestinal stem cells post-radiation, showcasing their versatility in biomedical research. In drug development, they facilitate screening for efficacy and toxicity, with applications in testing poly-ADP ribose polymerase (PARP) inhibitors and cosmetic ingredients, while aligning with ethical imperatives as the U.S. Food and Drug Administration (FDA) plans to phase out animal testing for certain drugs by 2025. In addition, organoids show promise in regenerative medicine, such as endometrial and retinal regeneration, and bone tissue engineering. Despite challenges such as variable culture conditions, limited vascularization, and high costs, standardizing protocols and integrating microenvironmental factors will enhance their clinical utility, driving a shift toward human-centric therapeutic advancements.

Considering the limitations of intraportal transplantation (Tx), we sought to establish an alternative approach for it-transplanting islets onto the liver surface (LS) by optimizing adipose tissue-derived stem cell (ADSC) co-Tx procedures with a gelatin hydrogel nonwoven fabric (GHNF). In the in vivo study, we examined the use of the GHNF, the effectiveness of islet covering materials, and preferred procedures for ADSC co-Tx using a syngeneic rat model. Immunohistochemical staining was performed to evaluate the extracellular matrix (ECM) expression and angiogenesis. In the in vitro study, we analyzed the culture supernatants to identify crucial factors secreted from ADSCs in different ADSC co-Tx procedures. It was shown that the GHNF should be used to cover the islets but not to embed internally (encapsulate) them. Utilization of the GHNF in LS Tx resulted in significantly better glucose changes (P = 0.0002) and cure rate of diabetic recipients (P = 0.0003) than the use of a common adhesion barrier. Although neovascularization was comparable among groups, ECM reconstitution tended to be higher when the GHNF was used. ADSC co-Tx further enhanced ECM reconstitution only when ADSCs were cultured in the GHNF before islet Tx. Leptin, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and several chemokines were identified as candidate factors for enhancing ECM reconstitution (P < 0.001). The inhibition assay using antagonist suggested that leptin might be at least in part responsible for the difference in transplant efficiency in distinct ADSC co-Tx methods. This study showed that the GHNF effectively improved the outcomes of LS islet Tx, mainly due to ECM reconstitution around the islets. Furthermore, we established a novel method of LS islet Tx by combining a GHNF with ADSCs, which is equally effective as intraportal Tx.

Long noncoding RNAs (lncRNAs) are crucial in porcine preimplantation embryonic development, yet their regulatory role during zygote genome activation (ZGA) is poorly understood. We analyzed transcriptome data from porcine fetal fibroblasts (PEF), induced pluripotent stem cells (iPS), and preimplantation embryos, identifying ZGA-specific lncRNAs like XLOC-040580, and further predicted its potentially interacting genes TPRA1 and BCL2L1 via co-expression network. XLOC-040580 was knocked down by siRNA microinjection and the expression of ZGA-related genes was detected by qRT-PCR. After microinjecting siRNA targeting TPRA1 and BCL2L1 at the one-cell stage, we counted the blastocyst development rate. The blastocyst development rate was consistent with the results from si-XLOC-040580 after si-TPRA1. Through dual-luciferase reporter assays, we found that XLOC-040580 was a downstream target of TPRA1. To further elucidate the mechanism of XLOC-040580, Single-cell mRNA sequencing after XLOC-040580 knockdown revealed its regulatory network involved in embryonic developmental defects. Transcriptome analysis revealed that XLOC-040580 was specifically expressed during zygote activation. Knockdown of XLOC-040580 decreased the blastocyst development rate and reduced both the total blastocyst cell number and TE cell number. TPRA1 and BCL2L1 were specifically co-expressed with XLOC-040580 during ZGA stage, and TPRA1 could interact with the promoter region of XLOC-040580 and regulate its expression. Knockdown of TPRA1 or XLOC-040580 blocked porcine embryonic development by affecting the expression of ZGA-related genes. We found and validated that lncRNA XLOC-040580 played a key role in the ZGA process, which was regulated by TPRA1. These results implied that the functional axis of TPRA1-XLOC-040580-downstream genes involved in ZGA-related functions also coordinated early embryonic development in porcine.

Neuropathic pain is a debilitating complication following spinal cord injury (SCI). Currently, effective treatments for SCI-induced neuropathic pain are highly lacking. This clinical trial aimed to investigate the efficacy of combined intrathecal injection of Schwann cells (SCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in improving SCI-induced neuropathic pain. This study was a parallel-group, randomized, open-label, active-controlled phase II trial with two arms, including treatment and control groups. Patients with complete SCI-induced neuropathic pain in the treatment group received a single combined intrathecal injection of BMSCs and SCs. Study outcome measures were International SCI Pain Basic Data Set (ISCIPBDS) and World Health Organization (WHO) Quality of Life Assessment Instrument (WHOQOL-BREF). A total of 37 (55.2%) and 30 (44.8%) patients in the treatment and control groups were followed up for 6 months, respectively. Significant reductions in mean scores of interference items in the treatment group, including daily activities (P < 0.001), mood (P < 0.001), and sleep (P < 0.001), were found at 6 months after the injection compared with the control one. Similarly, pain frequency (P = 0.002), mean (P = 0.001), and worst (P = 0.001) numeric rating scale (NRS) pain intensity scores showed significant reductions in the treatment group after 6 months compared with the control one. Based on multiple regression analysis controlled for potential confounders, significant associations between changes in all outcome measures over the study period and the treatment group were found. This clinical trial indicated the efficacy of combined cell therapy in improving the neuropathic pain and quality of life in complete SCI patients. Future investigations should evaluate the effects of combination of this strategy with other existing therapies for SCI-induced neuropathic pain. This clinical trial was also registered prospectively at the Iranian Registry of Clinical Trials (IRCT20200502047277N8).

Islet transplantation (IT) is a successful natural cell therapy. But the benefits are known mostly to individuals with severe type 1 diabetes who undergo IT and the health care professionals that work to make the therapy available, reproducible, and safe. Data linking IT to overall survival in T1D might alter this situation and frame the therapy in a more positive light. Recent analysis of mortality in several cohorts suggests that IT has possible survival benefits when used alone or in conjunction with renal transplantation. Multi-center prospective studies with long-term follow-up of individuals that receive stand-alone IT versus individuals who qualify for but do not undergo the procedure would seem reasonable to undertake to confirm an IT survival benefit.

To assess the impact of a single intra-articular (IA) injection of bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with knee osteoarthritis (OA), a randomized, double-blind, placebo-controlled study was conducted. The study included 24 patients with knee OA who were randomly assigned to receive either a single IA injection of BM-MSCs or normal saline. Changes in the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS) after IA injection were assessed at 3, 6, 9, and 12 months. Magnetic resonance imaging (MRI) with T2 mapping sequences was conducted for knee cartilage assessment at baseline and at 3 and 12 months. The MSC group showed between-group improvement in WOMAC (-5.0 ± 3.6 vs. -0.1 ± 5.5, P = 0.02) and KOOS (23.9 ± 18.3 vs. 7.2 ± 15.9, P = 0.028) scores at 9 months compared with the control group. The MSC group exhibited a less sharp increase in the mean T2 value of the medial compartment than the control group at 12 months, with no serious adverse events observed during follow-up. A single IA injection of allogeneic BM-MSCs provided satisfactory pain relief for patients with knee OA compared with the control group at 9 months. Quantitative T2 MRI mapping of the cartilage showed that IA BM-MSCs could have a preventive effect on OA progression for 12 months. Our findings suggest the potential of allogeneic BM-MSCs IA injection as a pain-relieving and disease-modifying treatment for patients with knee OA in the outpatient setting.

Organoids are three-dimensional (3D) cell cultures derived from human pluripotent stem cells or adult stem cells that recapitulate the cellular heterogeneity, structure, and function of human organs. These microstructures are invaluable for biomedical research due to their ability to closely mimic the complexity of native tissues while retaining human genetic material. This fidelity to native organ systems positions organoids as a powerful tool for advancing our understanding of human biology and for enhancing preclinical drug testing. Recent advancements have led to the successful development of a variety of organoid types, reflecting a broad range of human organs and tissues. This progress has expanded their application across several domains, including regenerative medicine, where organoids offer potential for tissue replacement and repair; disease modeling, which allows for the study of disease mechanisms and progression in a controlled environment; drug discovery and evaluation, where organoids provide a more accurate platform for testing drug efficacy and safety; and microecological research, where they contribute to understanding the interactions between microbes and host tissues. This review provides a comprehensive overview of the historical development of organoid technology, highlights the key achievements and ongoing challenges in the field, and discusses the current and emerging applications of organoids in both laboratory research and clinical practice.

The aim of this article is to identify whether bioactive glass (BG) is a valid substitute for autogenic bone grafting in maxillofacial reconstruction. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched. Meta-analyses with fixed- and random-effects models were performed by using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity was assessed by using the I² statistic. The significance of results was evaluated at P < 0.05. The BG leads to greater total bone volume retention 6 months after surgery compared with autografts (SMD = 0.796, 95% CI = 0.445-1.147, P = 8.74 × 10⁻⁶, I² = 0%). The resorption rate of BG grafts (SMD = -0.768, 95% CI = -1.360 to -0.176, P = 0.011, I² = 3.82%) was less common, while the retention of the biomaterial (SMD = 1.165, 95% CI = 0.540-1.790, P = 0.00026, I² = 0%) was higher in the experimental group. Both BG and autogenic grafts result in the formation of new bone to a similar extent. However, BG is able to provide long-term stability by maintaining the graft volume, reducing resorption, and preserving the graft scaffold, representing an effective alternative to autogenous bone grafting for a durable maxillofacial reconstruction.

Complex Regional Pain Syndrome Type I (CRPS-I) is a chronic neuropathic pain disorder characterized by peripheral nerve hyperexcitability and altered nociceptive signaling. Voltage-gated sodium channels (Nav1.7, Nav1.8, Nav1.9) in dorsal root ganglia (DRG) are key contributors to pain hypersensitivity. This study investigated the analgesic effects and underlying mechanisms of bone marrow mesenchymal stem cell (BMSC) transplantation in a CRPS-I rat model. The model was induced by hind limb ischemia-reperfusion, followed by intrathecal administration of BMSCs. Pain behaviors were assessed using thermal withdrawal latency (TWL), mechanical withdrawal latency (MWL), spontaneous pain scoring, and acetone-evoked cold allodynia. RT-PCR and Western blot analysis were used to evaluate Nav channel expression in DRG tissue, while electrophysiological properties were examined using whole-cell patch clamp to generate current-voltage (I-V) curves. CRPS-I rats exhibited decreased TWL and MWL, elevated expression of Nav1.7, Nav1.8, and Nav1.9, and enhanced sodium current density with delayed inactivation. BMSC transplantation significantly alleviated pain behaviors, downregulated sodium channel expression, and normalized I-V characteristics-marked by increased activation thresholds, reduced peak currents, and faster inactivation kinetics. These findings suggest that BMSCs mitigate neuronal hyperexcitability by modulating peripheral Nav channel activity. This study provides mechanistic evidence supporting the therapeutic potential of BMSC-based interventions for CRPS-I and related neuropathic pain conditions.