Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory properties, yet their precise mechanisms in alleviating Echinococcus multilocularis-induced hepatic inflammation and fibrosis in Alveolar Echinococcosis (AE) remain elusive. This study aimed to elucidate the immunoregulatory mechanisms underlying MSCs therapy in AE. Using an AE mouse model, we demonstrated that MSCs administration significantly ameliorated liver histopathology, attenuated fibrosis, and restored liver function. Molecular analyses revealed that AE infection promoted a pro-inflammatory profile (elevated RORγt and IFN-γ) while suppressing regulatory factors (FOXP3, TGF-β1, IL-10, CNTN1, and Gilz), effects that were robustly reversed by MSCs treatment. In vitro, co-culture of CNTN1-knockdown MSCs with E. multilocularis antigen-stimulated CD4+ T cells demonstrated that CNTN1 deficiency impaired MSCs-mediated immunoregulation, decreased IL-10 secretion, and disrupted the Th17/Treg balance. Mechanistically, dual-luciferase reporter assays confirmed that CNTN1 directly activates the Gilz promoter. Collectively, our findings identify the CNTN1/Gilz signaling axis as an essential mediator of MSCs immunomodulation, providing novel mechanistic insights into the therapeutic efficacy of MSCs against E. multilocularis-induced hepatic injury.
Mesenchymal stem cells (MSCs) exhibit potent immunomodulatory properties, yet their precise mechanisms in alleviating Echinococcus multilocularis-induced hepatic inflammation and fibrosis in Alveolar Echinococcosis (AE) remain elusive. This study aimed to elucidate the immunoregulatory mechanisms underlying MSCs therapy in AE. Using an AE mouse model, we demonstrated that MSCs administration significantly ameliorated liver histopathology, attenuated fibrosis, and restored liver function. Molecular analyses revealed that AE infection promoted a pro-inflammatory profile (elevated RORγt and IFN-γ) while suppressing regulatory factors (FOXP3, TGF-β1, IL-10, CNTN1, and Gilz), effects that were robustly reversed by MSCs treatment. In vitro, co-culture of CNTN1-knockdown MSCs with E. multilocularis antigen-stimulated CD4 + T cells demonstrated that CNTN1 deficiency impaired MSCs-mediated immunoregulation, decreased IL-10 secretion, and disrupted the Th17/Treg balance. Mechanistically, dual-luciferase reporter assays confirmed that CNTN1 directly activates the Gilz promoter. Collectively, our findings identify the CNTN1/Gilz signaling axis as an essential mediator of MSCs immunomodulation, providing novel mechanistic insights into the therapeutic efficacy of MSCs against E. multilocularis-induced hepatic injury.
Conventional therapies for endocrine hormone deficiencies, including hormone replacement therapy and solid organ transplantation, are hampered by the lack of physiological regulation or donor shortage, respectively. Directed differentiation of human pluripotent stem cells has opened new avenues for cell replacement therapy; however, research on different endocrine glands has long been conducted in isolation, with limited cross-disciplinary exchange of technical expertise. This Review takes the clinically most advanced stem cell-derived pancreatic β cells as a methodological reference and establishes a three-tier translational challenge model—cell identity, in vivo survival, and functional delivery—to systematically compare the regenerative progress and specific hurdles of thyroid, parathyroid, pituitary, and adrenal cells. We highlight transferable strategies emerging from these lineage-specific studies, including temporal developmental signaling modulation, modular lineage assembly, prevascularization engineering, and hierarchical immunocompatibility design. Through this cross-lineage comparative framework, this Review aims to break the isolated research paradigm and provide a methodological foundation for endocrine regenerative medicine to evolve from isolated efforts toward synergistic advancement.
Genetically engineered porcine red blood cells (pRBCs) are emerging as a potential supplementary source of oxygen-carrying cells for transfusion medicine. Triple-knockout (TKO) pigs lacking major carbohydrate xenoantigens, including Gal, Neu5Gc, and Sd(a), have substantially reduced human antibody binding in vitro, and additional expression of human protective molecules such as CD55 and CD47 may further improve compatibility. However, the translational development of pRBC xenotransfusion is now constrained less by donor engineering alone than by the absence of an appropriate in vivo evaluation model. Old World nonhuman primates have historically served as essential preclinical models in xenotransplantation, but their cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH)-positive background and natural antibody repertoires may exaggerate immune barriers to TKO pRBCs that are not fully representative of humans. New World nonhuman primates, brain-dead human models, and eventually carefully regulated early-phase human studies each offer distinct advantages and limitations. In this Commentary, we argue that pRBC xenotransfusion requires a purpose-specific translational framework rather than reliance on a single preclinical model. Such a framework should integrate standardized compatibility testing, in vitro human assays, animal-based safety stress-testing, and, where ethically and legally feasible, short-term human reference models.
Human herpesvirus 7 (HHV-7) encephalitis commonly occurs in immunocompromised individuals and has a poor prognosis. We here reported 3 cases of HHV-7 encephalitis following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with typical neurological symptoms, including altered consciousness and epileptic seizures, and conducted a systematic review of the literature to identify clinical characteristics and management strategies in these patients. Cerebrospinal fluid next-generation sequencing (NGS) was the key evidence that led to their diagnosis. Foscarnet and cidofovir appeared effective, particularly with at least four weeks of treatment. All three patients showed at least partial improvement in neurological symptoms. Furthermore, a systematic search was conducted in PubMed, Google Scholar, and Web of Science to identify related cases. Clinical presentation, diagnostic findings, treatment strategies, and outcomes were analyzed. A total of 10 publications were included, together with our 3 cases, comprising 7 cases of HSCT recipients for detailed analysis. Our study suggested that early recognition and prompt antiviral therapy are critical for improving prognosis. Further exploration is needed regarding risk factors and treatment strategies.
Donor-specific immunomodulatory cells (DSIMC) have successfully induced donor-specific tolerance in clinical living donor liver transplantation. These cells are generated from recipient peripheral blood mononuclear cells (PBMCs) stimulated with irradiated donor PBMC in the presence of costimulatory blockade, yielding a heterogeneous population of recipient-derived immune cells including T cells, B cells, and NK cells, in which CD4 + regulatory T cells (Tregs) are thought to play a central role. Here, we examined the cell populations and functions crucial for donor-specific immunomodulation within the DSIMC product. DSIMC were generated from PBMC of healthy volunteers using belatacept to achieve costimulatory blockade. Tregs were enriched by CD4 + CD25 + magnetic-cell activated cell sorting (MACS) or CD25 + CD127 -/low fluorescence-activated cell sorting (FACS). CD4 + , CD8 + , CD19 + , and CD25 + CD127 -/low fractions were also individually depleted from DSIMC. Immunomodulatory function of each resulting population was assessed by tritium-labelled thymidine incorporation in mixed lymphocyte cultures (MLC), and cytokine-producing capacity was evaluated by ELISA/ELISpot assays. Unsorted DSIMC exhibited donor-specific suppression at lower cell numbers than CD4 + CD25 + enriched cells, while CD4 + CD25 - T cells showed no immunosuppressive effect. Depletion of CD4 + , CD8 + , or CD19 + cells did not substantially impair immunomodulatory function. In contrast, depletion of the CD25 + CD127 -/low fraction reduced inhibitory function and abolished donor specificity. Depletion of CD4 + or CD25 + CD127 -/low reduced IFN-γ and IL-10 production in response to donor stimulation compared with unsorted DSIMC, implicating CD4 + Tregs as important contributors to cytokine production under allogeneic stimulation. Furthermore, Treg expansion following donor antigen restimulation was observed in unsorted DSIMC but not in CD4 + CD25 + -enriched cells, suggesting that Tregs can be induced from non-Treg CD4 + populations within the DSIMC. In conclusion, CD4 + CD25 + CD127 -/low FoxP3 + -associated cells appear to contribute to donor-specific immunomodulation; however, the enrichment of CD4 + CD25 + T cell diminished DSIMC efficacy. Since the unsorted DSIMC showed stronger activity, we suggest that multiple cell populations may act together to mediate the DSIMC effect.
Bioengineered livers using decellularized extracellular matrix (ECM) scaffolds hold promise for transplantation therapies. However, conventional recellularization methods involving cell injection via blood vessels encounter challenges in recapitulating the complexity of hepatic tissues, including high cellularity, differentiation hierarchy, and cellular heterogeneity. Here, we developed a methodology termed “combined single-cell and organoid (CSO) injection.” We injected human liver organoids (HLOs) and dispersed organoid cells via direct puncture and vascular injection into a decellularized porcine ECM scaffold, respectively. This process facilitated the construction of densely populated and self-organized liver-like tissues (CSO Livers) that formed cell-cell/cell-ECM interactions. The tissues displayed hepatic characteristics, including ALBUMIN secretion, robust expression of liver-associated genes, and cellular heterogeneity comprising hepatocytes, cholangiocytes, as well as stellate-like and endothelial cells. Furthermore, we demonstrated that CSO-Livers functioned as grafts in immunodeficient mice and in a microminipig model of liver fibrosis through transplantation via vascular anastomosis. These findings indicate the applicability of the combined single-cell and organoid (CSO) injection method for generating bioengineered liver grafts using HLOs.
Radiation-induced brain injury (RIBI) is a serious complication of cranial radiotherapy and currently lacks effective disease-modifying treatment. Persistent neuroinflammation and neurovascular dysfunction are considered central to RIBI progression, making them attractive therapeutic targets for regenerative intervention. Multilineage-differentiating stress-enduring (Muse) cells are a non-tumorigenic pluripotent-like cell population with reported reparative and immunomodulatory properties, but their therapeutic potential in RIBI has not been defined. In this study, we evaluated the effects of Muse cell transplantation in experimental RIBI using in vitro neurovascular co-culture systems and in an vivo rat model. Irradiation induced marked activation of inflammasome-related signaling, endothelial injury, and neurological impairment. Muse cells suppressed the expression of NLRP3, AIM2, ASC, Caspase-1, IL-1β, and IL-18 in irradiated co-culture systems, while preserving endothelial proliferative and angiogenic responses. Transcriptomic analysis identified stress-related pathways associated with Muse cell-mediated protection, and PPAN emerged as a candidate regulator linked to the reparative phenotype. In vivo, intracarotid transplantation of Muse cells reduced [18F] DPA-714 uptake in irradiated brain tissue and was accompanied by supportive behavioral trends suggestive of functional improvement. These findings provide exploratory preclinical evidence that Muse cell transplantation attenuates neuroinflammatory activation and preserves endothelial reparative responses after radiation-induced brain injury. Muse cells may therefore represent a potential cell-based strategy for RIBI, although their therapeutic efficacy, neurovascular repair-related effects, and long-term functional benefits require further validation in larger and more comprehensive preclinical studies.
Chronic graft-versus-host disease (cGVHD) remains the leading cause of late non-relapse mortality and long-term disability after allogeneic hematopoietic cell transplantation (allo-HCT), affecting 30–70% of long-term survivors. Despite its substantial morbidity and the toxicities associated with prolonged corticosteroid use, therapeutic advances have accelerated considerably. This review synthesizes current mechanistic insights and clinical evidence within the framework of the well-established three-phase pathogenesis model of cGVHD. Phase 1 (early inflammation) involves tissue injury and innate immune activation; Phase 2 (months 2–12) is characterized by impaired central and peripheral tolerance with aberrant B- and T-cell responses; Phase 3 (>1 year) features macrophage-driven fibrosis and end-organ damage. Recognizing that these phases are conceptual and frequently overlap in clinical practice, we explore the alignment of contemporary biomarkers with each phase—ST2/CXCL9 (Phase 1), BAFF/autoantibodies (Phase 2), and MMP3/TGF-β (Phase 3)—and discuss how FDA-approved agents (ibrutinib, ruxolitinib, belumosudil, axatilimab) may target phase-specific pathways. A conceptual, risk-stratified treatment algorithm is proposed to link pathobiology to clinical decision-making, with the important caveat that biomarker-guided selection remains investigational and currently complements, rather than replaces, comprehensive clinical assessment. Notably, the adoption of prophylaxis and upfront strategies to prevent cGVHD has substantially reduced cGVHD incidence in modern cohorts.
Islet transplantation is a promising treatment for diabetes, but the shortage of donor islets limits its broad application. Induced pluripotent stem cells (iPSCs) provide an alternative source for generating insulin-producing cells; however, whether the somatic cell origin of human iPSCs influences pancreatic endocrine differentiation remains incompletely defined. In this study, we generated iPSCs from human pancreatic duct cells (HD-iPSCs) and compared their differentiation propensity and functional characteristics with human fibroblast-derived iPSCs (HF-iPSCs) under identical differentiation conditions. HD-iPSC-derived cells showed higher expression of pancreatic endocrine and β-cell-associated markers, including insulin, PDX1, and FOXA2, compared with HF-iPSC-derived cells. Flow cytometric analysis further confirmed a higher proportion of insulin-positive cells in differentiated HD-iPSC-derived cells. Functionally, HD-iPSC-derived cells exhibited greater glucose-stimulated C-peptide secretion than HF-iPSC-derived cells, although their secretory capacity remained lower than that of native human islets. Following transplantation into streptozotocin-induced diabetic mice, HD-iPSC-derived cells reduced blood glucose levels more effectively than HF-iPSC-derived cells, and insulin-positive grafts were detected in vivo. These findings suggest that human pancreatic duct cell-derived iPSCs have enhanced pancreatic endocrine differentiation potential compared with fibroblast-derived iPSCs. Although further maturation and optimization are required, pancreatic duct cells may represent a favorable somatic cell source for generating iPSC-derived insulin-producing cells for diabetes cell therapy.
To investigate the efficacy and safety of MTBF as conditioning regimen for salvage allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with relapsed or refractory acute myeloid leukemia (R/R AML). We conducted a single-arm prospective clinical trial (NCT06385808). The main outcome was cumulative incidence of relapse (CIR), and the secondary outcomes were progression-free survival (PFS), overall survival (OS), engraftment time, graft-versus-host disease (GVHD), and non-hematological adverse effects. Twenty-four R/R AML patients from the First Affiliated Hospital of Xi'an Jiaotong University were enrolled, and all achieved engraftment. Mucositis was the predominant toxicity and was managed appropriately. The two-year CIR was 10%. The two-year OS and PFS were 78.9 ± 11.1% and 51.2 ± 19.3%, respectively. Two patients experienced relapse, and three patients died of infection. Subgroup analyses demonstrated that maintenance treatment post-transplantation may improve OS. The MTBF regimen for salvage allo-HSCT in R/R AML exhibited notable anti-leukemia activity and tolerable toxicity. (NCT06385808, Efficacy and Safety of MTBF Conditioning Regimen for Salvageable Allo-HSCT in the Treatment of R/R AML).
Stromal vascular fraction (SVF)-based therapies and autologous fat grafting have emerged as promising regenerative strategies due to their pro-angiogenic, immunomodulatory, and trophic properties. However, despite encouraging preclinical and clinical findings, therapeutic outcomes remain highly heterogeneous, with marked variability in graft retention and functional efficacy between patients. Increasing evidence suggests that this variability cannot be explained solely by procedural factors or cellular composition, but may also depend on host-related immune and microenvironmental determinants. This review explores the biological mechanisms governing SVF engraftment and introduces the emerging concept of “SVF therapy resistance,” defined as the failure of autologous regenerative therapies resulting from maladaptive interactions between transplanted stromal cells and the host tissue environment. Particular attention is given to sterile inflammation, innate immune activation, and early graft–host interactions. Following transplantation, tissue injury and ischemia induce the release of danger-associated molecular patterns (DAMPs), triggering neutrophil recruitment, macrophage activation, complement signaling, and inflammatory remodeling. While controlled inflammatory responses may support tissue repair and angiogenesis, excessive neutrophil activation, neutrophil extracellular trap (NET) formation, persistent pro-inflammatory macrophage polarization, and impaired vascular adaptation may compromise graft survival and regenerative efficacy. The review further discusses how SVF processing, inflammatory priming, stromal cell heterogeneity, and donor-related factors—including obesity, aging, metabolic dysfunction, and chronic inflammation—may influence therapeutic responsiveness. Emerging evidence from mesenchymal stromal cell biology suggests that stromal cells are highly sensitive to inflammatory licensing and microenvironmental cues. Candidate biomarkers and immune profiling strategies capable of identifying responders and non-responders to SVF-based therapies are also reviewed. Finally, these mechanisms are discussed in spinal cord injury, a condition characterized by chronic inflammation and vascular dysfunction. Overall, this review proposes a translational framework linking innate immunity, sterile inflammation, angiogenesis, and stromal cell heterogeneity to the variability of SVF therapy outcomes, highlighting the need for personalized regenerative medicine approaches.
Myocardial infarction (MI), mainly caused by coronary artery occlusion, remains a leading cause of death worldwide. Although many patients survive after emergency treatment, chronic MI often develops, underscoring the need for effective therapies. This study evaluated the therapeutic potential of human umbilical mesenchymal stromal cells (HUMSCs) in a rat model with chronic MI. MI was induced by permanent ligation of the left anterior descending artery. Seven days post-ligation, 4×10 6 HUMSCs were transplanted into the peri-infarct myocardium, while an additional 2.5×10 7 HUMSCs were introduced into the mediastinal space around the ligation site. Successful model establishment was confirmed by elevated cardiac biomarkers and characteristic electrocardiographic changes. Echocardiography and magnetic resonance imaging demonstrated significant impairments in myocardial strain dynamics, reduced ejection fraction, and diminished fractional shortening, all of which improved following HUMSC transplantation. The transplantation also reduced macrophage infiltration, increased M2 macrophage polarization, suppressed fibroblast activation, attenuated fibrosis, and promoted angiogenesis, ultimately preserving cardiomyocytes and improving cardiac function. The transplanted HUMSCs were detected in rat’s myocardium without differentiating into cardiomyocytes or endothelial cells. These findings suggest that adequate HUMSC transplantation offers a promising therapy to attenuate progression of chronic MI or heart failure.
Craniomaxillofacial (CMF) bone defects pose significant regenerative challenges due to complex anatomy and physiological demands. While autologous bone grafting remains the gold standard, it is limited by donor-site morbidity and supply constraints. Mesoporous bioactive glass (MBG), characterized by its ordered nanoporous structure and superior bioactivity, offers a promising alternative. This review systematically analyzes the integration of MBG with 3D printing technologies, including direct ink writing, stereolithography, selective laser sintering, and fused deposition modeling. We critically evaluate physicochemical challenges such as rheological optimization and thermal devitrification while elucidating the “osteo-immune-vascular” axis orchestrated by these scaffolds. Specifically, we discuss how ionic dissolution products modulate macrophage polarization, stabilize hypoxia-inducible factor-1α (HIF-1α) to induce CD31ʰⁱEmcnʰⁱ vessel formation, and activate Wnt/β-catenin signaling. Despite promising preclinical data, clinical translation faces hurdles regarding regulatory approval and manufacturing standardization. Future developments in 4D printing, AI-driven inverse topology design, and organ-on-a-chip validation represent a paradigm shift from passive substitution to active regeneration, paving the way for the tissue-engineered reconstruction of complex CMF defects.
Ligament injuries can lead to lasting instability and early joint degeneration despite rehabilitation or surgery. Stem cell therapies may aid regeneration, but studies are highly variable. Bibliometric analysis can summarize trends, hotspots, and research gaps. We searched the Web of Science Core Collection for English-language original articles on stem cell therapy for ligament injuries from 2001 to 2025 on April 2, 2025, excluding non-original publications. Publication and citation trends were summarized, and co-authorship, co-citation, and keyword networks were mapped using Excel, VOSviewer, CiteSpace, and Bibliometric.com. A total of 599 articles were included, with steadily increasing annual publications. The United States and China were leading contributors, with strong collaboration networks involving major institutions such as the University of Pittsburgh and Zhejiang University. Keyword analyses identified seven main themes spanning mechanisms, clinical translation, tissue engineering, surgery/grafting, injury models, biomechanics, and biomaterials. Recent hotspots included "inflammation" and "artificial ligament". Stem cell research for ligament injuries is increasingly focused on mechanisms and biomaterials, but evidence is still mainly preclinical and inconsistent. Better comparative clinical studies and standardized, well-defined biomaterial-cell approaches are needed.
Amniotic epithelial cells (AECs) have immunomodulatory and anti-inflammatory properties that may improve outcomes in cell transplantation. However, their effect on islet engraftment after intraportal co-transplantation remains unclear. We evaluated the impact of co-transplanting syngeneic 600 islet equivalents (IEQs) with human AECs (hAECs) via the portal vein in a rat streptozotocin-induced diabetes model. The co-transplantation (Co-Tx) group showed normalization of blood glucose levels within 7 days after transplantation, sustained normoglycemia thereafter, and achieved a higher diabetes reversal rate than controls (100% vs. 71.4%, p < 0.01). Serum CXCL1 levels were significantly lower in the Co-Tx group indicating suppression of early inflammatory responses. Thrombin-antithrombin complex (TAT) levels also tended to be lower, raising the possibility of attenuation of the instant blood-mediated inflammatory reaction (IBMIR). In contrast, no significant differences were observed in VEGF levels or intrahepatic microvascular density. Co-transplantation with hAECs enhances islet engraftment likely through suppression of early inflammation, highlighting their potential as an adjunctive cellular therapy in islet transplantation.
Organ-on-a-chip (OoC) platforms are microengineered systems that combine microfluidic control with living cells to emulate the physiological functions of human tissues and organs in vitro. OoC has become a transformative tool in pharmaceutical research, offering unprecedented capabilities for predicting drug efficacy, pharmacokinetics, and toxicity with human-relevant precision. This study presents a comprehensive scientometric and patent landscape analysis of OoC studies in pharmaceutical sciences spanning 2008-2025. Using CiteSpace, we mapped 1,786 publications to identify influential authors, landmark works, and temporal shifts in thematic focus. Keyword burst and clustering analyses reveal emerging frontiers in multi-organ integration, disease modeling, and drug screening. Patent data indicate a rapid expansion since 2016, led by China and the United States, underscoring a translational trajectory from fundamental research to applied biotechnology. These findings delineate the evolving intellectual and technological framework of organ-on-a-chip research in drug development and highlight future priorities in multi-organ systems, biomaterials optimization, and clinical translation.
Peripheral nerve injury (PNI) often results in persistent functional deficits, and current treatments remain suboptimal. This study developed a tissue-engineered graft by integrating Cdc42-modified bone marrow-derived mesenchymal stem cell (BMSC)-derived exosomes (Exos-Cdc42) with an acellular nerve allograft (ANA) and evaluated its therapeutic potential for nerve regeneration and functional recovery. Exosomes were isolated from BMSCs, and Exos-Cdc42 were generated by transfecting these cells with Cdc42 overexpression vectors. In vitro, Exos-Cdc42 significantly enhanced Schwann cell proliferation, migration, and secretion of neurotrophic factor (BDNF, NGF, CNTF), while upregulating repair-associated markers and downregulating myelination-related markers. In vivo, the combination of Exos-Cdc42 and ANA improved functional recovery of the sciatic nerve, as evidenced by higher sciatic functional index scores and increased muscle weight. Histological analyses demonstrated enhanced axonal regeneration and myelination, characterized by thicker myelin sheaths and larger axon diameters. These findings suggest that Exos-Cdc42 enhance the therapeutic efficacy of ANA by promoting Schwann cell-mediated repair responses, representing a promising strategy for peripheral nerve regeneration.
Human pancreatic islets are essential for studies in β-cell biology, cell transplantation, and tissue engineering, yet access to viable human islets remains limited because conventional isolation protocols primarily rely on whole pancreases from deceased donors. Surgical pancreatectomy specimens may represent an accessible alternative source, but factors influencing successful isolation and functional preservation remain poorly defined. In this study, we evaluated a standardized method for isolating human islets from pancreatic tissue obtained from surgical pancreatectomy specimens and investigated patient-, specimen-, and surgery-related factors affecting islet yield and functionality. Between March and October 2024, 50 consecutive islet isolations were performed from pancreatic specimens obtained during surgical resections. Following enzymatic digestion, tissue fractions were cultured for 24 h before handpicking of morphologically intact islets. Islet yield was quantified as islet equivalents (IEQ), and functional integrity was assessed by glucose-stimulated insulin secretion assays on culture days 1, 3, and 5. A mean yield of 6690 IEQ/g pancreatic tissue was obtained (range 0–56,500 IEQ/g). Exploratory analyses suggested potential associations between islet yield and factors such as younger patient age, shorter surgical duration, and preserved pancreatic parenchyma. However, these findings should be interpreted cautiously given the variability of the specimens and the exploratory design of the study. These findings support the feasibility of using surgical pancreatectomy specimens as an accessible source of functional human islets for experimental and translational research.
This study aimed to define the incidence of Clostridioides difficile infection (CDI), identify its risk factors, and evaluate its association with early post-transplant complications and overall clinical outcomes. To characterize CDI in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) setting, we retrospectively analyzed a cohort of 539 recipients who experienced diarrhea in the peri-transplant period (from conditioning to discharge from laminar flow). Among these diarrheic recipients, 64 patients developed CDI, the cumulative incidence of CDI was 12.1%, with a median onset of day -1 (range, -7 to +26) relative to HSCT. In a multivariate analysis, older age was independently associated with a lower risk of CDI (HR, 0.97; P = 0.008) among diarrheic recipients. The incidence of CDI stratified by the median onset time revealed that pre-transplant CDI was an independent risk factor for grade 1-4 lower gastrointestinal acute graft-versus-host disease (lower-GI aGVHD) (HR, 2.43; P=0.024). Furthermore, pre-transplant CDI was associated with a markedly increased risk of severe fungal infection (HR,6.97; P=0.026) and 100-day non-relapse mortality (NRM) (HR, 3.13; P=0.046). In conclusion, this study highlights a critical, timing-dependent distinction in CDI-associated severe complications and mortality in allo-HSCT recipients with diarrhea.
