Cell Transplantation最新文献

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.

Donor-specific antibodies (DSAs) are essential causes of graft rejection in haploidentical hematopoietic stem cell transplantation (haplo-HSCT). DSAs are unavoidable for some patients who have no alternative donor. Effective interventions to reduce DSAs are still needed, and the cost of the current therapies is relatively high. In this study, we retrospectively analyzed the data of 11 DSA-positive patients who received haplo-HSCT at our center and evaluated the therapeutic efficacy of the combination of intravenous immunoglobulin (IVIG), dexamethasone and high dose of transfused mononuclear cells (MNCs) for DSA desensitization. The kinetics of DSAs at different times and the engraftment and transplantation outcomes were also observed. We found that all patients had successful donor-cell engraftment and that no patient developed poor graft function. The median engraftment times of neutrophils and platelets were 14 days (range, 11-24 days) and 13 days (range, 11-123 days), respectively. The DSA levels of all patients became negative or dropped under 2000 within 22 days after HSCT. A total of 36.4% of patients developed grade II-IV acute graft-versus-host disease (aGVHD), and 9.1% of patients died of severe gastrointestinal aGVHD. Of the 7 surviving patients, four were diagnosed with chronic GVHD. After a median follow-up of 28.9 months (2.0-52.1 months), four patients died: of relapse (two), aGVHD (one), and multiple-organ failure (one). The 2-year OS, DFS, and NRM were 63.6%, 45.4%, and 18.2%, respectively. Combination therapy with IVIG, dexamethasone, and a high dose of MNCs transfusion, a simple and efficient procedure, was safe and effective for DSA desensitization and peripheral blood stem cell (PBSC) engraftment.

Schwann cell (SC) transplantation is considered as a promising strategy for spinal cord injury. However, SCs show less capability in assisting the regenerative axons to penetrate through astrocyte (AS)-formed scar barrier. Anosmin-1, an extracellular matrix glycosylated adhesion protein expressed in the olfactory bulb, is involved in olfactory ensheathing cells and reborn olfactory nerve axons continually penetrating the glial barrier and targeting the olfactory bulb. In this study, we employ a dorsal root crush injury model treated with anosmin-1. A vertical climbing test was used for behavioral analysis and immunohistochemical study for SC/AS interaction in regenerative axon targeting. Anosmin-1 improved rat forepaw grasping as revealed by forelimb proprioception assessment. After treated with anosmin-1, p75+ immature SCs and P0+ mature SCs mingled well with ASs at the peripheral/central glial interface, reforming the glial barrier from a tight to loose structure. Furthermore, regenerated axons traced by BDA staining revealed proper axonal targeting to the dorsal horn of the spinal cord. These results suggest that anosmin-1 can regulate SC/AS interactions at the peripheral/central boundary site to open the glial barrier for regenerating axons crossing, targeting, and establishing functional neuronal circuits. Anosmin-1 might have a potential application in repair of spinal cord injuries, particularly in combination with SCs for autologous cell transplantation.

Pediatric organ transplant recipients have a higher risk for wait list mortality due to the scarcity of size matched organs. Neonatal organ donation could potentially ameliorate the discrepancy but is currently not implemented in Sweden. This study aims to evaluate the potential of neonatal organ donation in central Sweden using a standardized protocol with organ specific criteria. Data on 2,061 neonates who deceased in central Sweden from 2006 to 2016 were collected; 308 neonates met criteria for possible donation. Medical records of all possible donors were reviewed, identifying 85 potential donors. Main cause of death was hypoxic ischemic encephalopathy 47% (n = 40). Median weight was 2,355 (IQR: 1,953) g, with 31% receiving inotropic support. Median creatinine of 72 (IQR: 67) µmol/l, urine production 3 (IQR: 2.2) ml/kg/h, ALT 0.51 (IQR: 1.5) µkat/l, and AST 1.7 (IQR: 3.1) µkat/l. Criteria for kidney donation was met in 39 potential neonatal, 29 for liver and 18 for heart, corresponding to a potential increase of 1.9, 1.4, and 0.9 donors PMP per year, respectively. In total, 16 neonates had a catastrophic neurological injury in combination with lack of brainstem reflexes, indicating plausibility of donation after brain death. Expanding organ donation into the neonatal period in Sweden could lead to an increase in organs available for transplant.

Stem cell therapy has emerged as a promising strategy for inherited retinal diseases (IRDs), yet its global research trajectory has not been systematically mapped. This study analyzes publication trends, leading contributors, and thematic evolution of IRD stem cell therapy research from 2000 to 2024. Publications were retrieved from the Web of Science Core Collection and analyzed with CiteSpace and VOSviewer. We identified 1060 articles with a steady rise in annual output. The United States and China were the most prolific countries; University College London and the University of Iowa were major institutions; and key outlets included Stem Cell Research & Therapy, Investigative Ophthalmology & Visual Science, and Cell Transplantation. Keyword and co-citation analyses reveal a clear trajectory: early emphasis on stem cell-derived retinal pigment epithelium transplantation for photoreceptor rescue, subsequent expansion to photoreceptor precursor and retinal organoid replacement, and recent movement toward early clinical translation. Persisting challenges include long-term graft survival, functional integration, and immune compatibility. Overall, this bibliometric roadmap clarifies how the field is transitioning from foundational studies to translational application and highlights priorities for interdisciplinary collaboration to accelerate clinical advancement.

This study aimed to investigate whether soluble B-cell maturation antigen (sBCMA) levels could be predictive biomarker for short-term and long-term therapeutic efficacy and survival outcomes following anti-BCMA CAR-T cell therapy in relapsed/refractory multiple myeloma (R/R MM). We enrolled 29 R/R MM patients who received anti-BCMA CAR-T cell therapy. In short-term observation, proportion of MM cells, expression of B-cell maturation antigen (BCMA) and sBCMA in bone marrow (BM) were evaluated, along with adverse events, correlation between sBCMA levels and short-term efficacy or survival outcomes were evaluated. In long-term observation, expressions of sBCMA were observed up to 24 months after therapy or until disease progression again in patients who achieved an objective response (ORR). Progression-free survival (PFS), overall survival (OS), correlation between sBCMA levels, and long-term outcomes were analyzed. In short-term observation, high expressions of sBCMA in BM were associated with poor efficacy of CAR-T cell therapy, while the proportion of MM cells in BM and BCMA expression in MM cells were not associated with poor efficacy of therapy. After 2 months of infusion, sBCMA levels decreased significantly, especially in patients who obtained ORR. In long-term follow-up, for patients who achieved ORR, the sBCMA levels significantly increased again when their disease progressed once more. Notably, R/R MM patients with extramedullary disease (EMD) demonstrated a higher likelihood of disease progression again. In patients achieved ORR, peaks of CAR-T cells correlated with proportion of MM cells, not with BCMA and sBCMA expression. Additionally, sBCMA levels were independent of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) severity. We suggest that sBCMA levels in BM might serve as a predictive biomarker for anti-BCMA CAR-T cell therapy efficacy prior to treatment and for disease progression during long-term monitoring. The trail register name is China Clinical Trial Register. URL are https://www.chictr.org.cn/bin/project/edit?pid=28999 and https://www.chictr.org.cn/bin/project/edit?pid=53962. Registration numbers are ChiCTR1800017051 and ChiCTR2000033925.