Endometrial injury is the main cause of intrauterine adhesion (IUA), with dysregulated inflammatory signaling promoting fibrosis and dysfunction. Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) show potential for endometrial repair, but their molecular mechanisms remain unclear. This study isolated and characterized hUCMSCs and hUCMSC-Exos. We found that hUCMSC-Exos transplantation effectively reversed rat endometrial injury by restoring endometrial thickness, increasing gland number, attenuating inflammation and fibrosis, and upregulating proliferation marker expression. Moreover, hUCMSC-Exos enhanced proliferation, reduced pro-inflammatory cytokine levels, and increased anti-inflammatory/anti-fibrotic factor expression in Endometrial stromal cells (ESCs). Mechanistic studies confirmed that hUCMSC-Exos significantly downregulated mRNA expression of HMGB1, TLR4, and NF-κB while upregulating IκBα mRNA. Meanwhile, hUCMSC-Exos inhibited the protein expression and phosphorylation of HMGB1, TLR4, p-IκBα, and p-p65, upregulated IκBα protein. Additionally, Ethyl pyruvate(EP) and Ammonium pyrrolidinedithiocarbamate (PDTC) potentiated hUCMSC-Exos-mediated inhibition of the above pathway molecules' expression and phosphorylation, whereas recombinant high-mobility group box 1 (rHMGB1) significantly reversed this inhibitory effect. The results indicate that hUCMSC-Exos may modulate inflammation via the HMGB1/TLR4/NF-κB signaling pathway, which suggests a potential role of this pathway for endometrial injury repair.

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke worldwide and is characterized by complex pathophysiological mechanisms. Although its etiology and diagnostic criteria are well-established, an optimal therapeutic strategy remains under active debate. Stem cell therapy has been extensively investigated for the treatment of neurological diseases over the past decade, and mesenchymal stem cell (MSC)-based therapies have emerged as a promising strategy for ICH treatment. However, accumulating evidence suggests that the therapeutic effects of MSC-based therapies are primarily mediated by the paracrine activity of MSCs. Moreover, although MSC-based therapy for ICH offers several advantages, the transplantation method and post-transplantation cell survival remain critical determinants of therapeutic efficacy. Recent advances in optimizing MSC transplantation protocols and improving post-transplantation cell survival have shown promising results. This review focuses on the research progress of MSCs in ICH therapy and the challenges involved in translating these findings from experimental to clinical applications.

Full-thickness skin equivalents (FTS) reproduce epidermal stratification, yet rarely generate hair follicles or glands. Defining the cellular features associated with this limitation could inform the engineering of appendage-bearing skin. Here we profiled mouse induced pluripotent stem cell-derived early epithelial progenitors (EEPs) and EEP-derived FTS by single-cell RNA sequencing, using developing mouse skin as a reference. FTS established a stratified epidermis with basal cell enrichment, but was accompanied by a marked reduction in appendage-primed cells (1.17% versus 8.69% in EEPs). Developmental mapping showed that FTS cells mapping to the hair follicle trajectory concentrated at early positions, whereas EEPs spanned a later and broader correspondence. Compared with matched developing skin states, FTS epithelium exhibited stronger injury-response and reactive transcriptional programmes. This epithelial reactivity coincided with an inferred dermal-epithelial signalling network with weaker BMP and noncanonical WNT inputs, no epithelial Hedgehog communication, and biased FGF and extracellular matrix interactions. Together, these findings link limited appendage formation in FTS to reduced appendage priming, a reactive interfollicular epidermal state, and a remodelled dermal signalling environment that diverges from native developmental niches.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only treatment with curative potential for myelodysplastic syndromes (MDS). This review synthesizes MDS-specific evidence on transplant indication and timing, conditioning, donor choice, molecular predictors, and post-transplant surveillance. Prospective biologic-assignment studies support a survival benefit in fit older adults with higher-risk MDS. The Molecular International Prognostic Scoring System (IPSS-M), transplant-specific cytogenetic and mutational factors, comorbidity, and transfusion burden refine selection beyond the Revised International Prognostic Scoring System (IPSS-R). Alternative donors expand access, including haploidentical transplantation with post-transplant cyclophosphamide. Conditioning intensity should reflect both disease risk and patient fitness, with regimen-level scoring emerging for cord blood transplantation. Although non-relapse mortality has decreased over time, relapse remains the major unresolved cause of failure. MDS-specific measurable residual disease, graft-versus-host disease, cytomegalovirus assessment, and risk-adapted post-transplant interventions provide a practical framework for individualized care.

BackgroundTo evaluate the safety and efficacy of intranasal transplantation of ANGE-S003 human neural stem cells (hNSCs) in early-onset Parkinson's disease (EOPD) patients with motor complications.MethodsIn this randomized, double-blind, placebo-controlled trial, 24 EOPD patients were randomized (2:1) to receive weekly intranasal administrations of 1.5 × 10[7] hNSCs or placebo for 4 weeks, followed by 12 months of follow-up. The primary endpoint was change in MDS-UPDRS Part IV score at month 6.ResultsNo significant difference was observed in the primary endpoint (least-squares mean difference, 0.42; 95% CI, -4.29 to 5.13; P = 0.853). Controls showed greater worsening of off-state MDS-UPDRS Part III motor scores in non-onset limbs at 12 months (P = 0.029). Exploratory 11C-CFT PET analyses demonstrated greater reductions in dopaminergic activity in the non-onset caudate (P = 0.022) and anterior putamen (P = 0.045) in controls versus the treatment group. A total of 137 adverse events and 6 serious adverse events were reported.ConclusionsAlthough the primary endpoint was not met, motor and neuroimaging findings provide preliminary signals of a potential treatment effect. Larger studies are needed to confirm efficacy and safety.

Deer antlers are the only mammalian appendage capable of complete regeneration, with antler stem cells (AnSCs) playing a central role in this process. Extracellular vesicles (EVs) secreted by AnSCs function as the key paracrine mediators that mediate the multifaceted biological functions of these stem cells. Herein, we systematically review the research progress in the discovery, characterization, therapeutic applications, and scalable expansion technologies of AnSCs and their EVs. AnSCs exhibit the properties of both embryonic stem cells and mesenchymal stem cells, and their EVs have low immunogenicity and high bioactivity, demonstrating the remarkable application potential in regenerative medicine. Although current studies have elucidated some of their key functions and mechanisms, critical challenges remain for the development of therapeutic agencies, including the standardized procedure of production, establishment of quality control systems, and identification of molecular targets. This review summarizes current advances in AnSCs and their EVs, aiming to provide a new avenue for subsequent clinical translation and industrial application.

Cell transplantation therapies for Parkinson disease (PD) require confirmation that grafted tissue withstands the degenerative environment of the diseased brain. Autologous peripheral nerve tissue (PNT) grafts transplanted into the substantia nigra (SN) have been investigated in an ongoing clinical program, but characterization of graft survival after extended periods in the human CNS has been limited. We present histological and immunohistochemical analysis of PNT grafts in postmortem tissue from two participants who lived 7 years 11 months and 9 years 2 months following transplantation. Grafts persisted as structurally organized tissue with preserved fascicular architecture, compartmentalized boundaries defined by convergent GFAP-negative and COL1A1-positive demarcation, and cellular density comparable to naïve sural nerve. Immune cell presence within grafts was limited (4-7%) and concentrated at graft-host interfaces. Vascular networks including CD31-positive capillaries and SMA-positive arterioles were identified within grafts. Transplanted tissue maintained PNS identity with Schwann cell markers p75NTR, S100B, and MPZ detected within grafts, contrasting MBP expression in surrounding parenchyma. TH-positive processes within grafts, spatially associated with MPZ immunoreactivity, supported interactions between grafted Schwann cells and catecholaminergic processes consistent with dopaminergic origin. These findings provide histological evidence that autologous PNT grafts persist as organized, cellularly viable, transplanted tissue with maintained PNS identity after extended survival in the parkinsonian SN.

Patients with relapsed or refractory primary breast lymphoma (r/r PBL) face a poor prognosis, and data regarding chimeric antigen receptor (CAR) T-cell therapy for this specific population remain scarce. This retrospective study aimed to evaluate the clinical efficacy and toxicity of CAR T-cell therapy (CD19 or sequential CD19/CD22), administered either alone or combined with autologous stem cell transplantation (ASCT), in 11 adult patients with r/r PBL. The cohort included nine patients with diffuse large B-cell lymphoma and two with Burkitt lymphoma. The treatment demonstrated high efficacy: at three months post-treatment, the overall response rate was 81.8%, and the complete remission rate was 72.7% (eight patients). Over a median follow-up of 38 months, seven patients remained alive, yielding estimated 1-year overall and progression-free survival rates of 63.6% and 61.4%, respectively. Notably, the safety profile was highly favorable; no patients experienced grade 3-4 cytokine release syndrome or any grade of immune effector cell-associated neurotoxicity syndrome. In conclusion, CAR T-cell therapy, with or without ASCT, represents a highly effective and safe therapeutic strategy for adult patients with r/r PBL, offering durable remissions with manageable toxicities.

Regeneration of dental pulp has surfaced as an exciting area of exploration in regenerative endodontics, as a result of progress in stem cell biology and their applications, along with biomaterials. Of the different cell populations studied, dental pulp stem cells (DPSCs) are recognized as possessing significant regenerative potential considering their multipotency, immunomodulatory properties and capacity to differentiate into odontoblast-like cells. Interest has also increased in alternative approaches, such as the DPSC-derived secretome, which serves as a bioactive consulting of molecules like cytokines, growth factors and extracellular vesicles, to initiate regenerative processes through paracrine signalling without the limitations of cell-based treatments. This review highlights the relative therapeutic potential of DPSCs secretome when integrated with three-dimensional scaffolds for the regeneration of the pulp-dentin complex. We discuss the biological mechanisms by which DPSCs secretome helps in regeneration assess the compatibility of scaffolds, and review advantages and limitations regarding their use based on efficacy, immunogenicity, storage and clinical use. Although DPSC scaffolds provide direct tissue reconstruction, secretome-enhanced scaffolds are clinically applicable as a cell-free, scalable and potentially safer method. A better understanding of the advantages and disadvantages of DPSC secretome-modified scaffolds will assist in the development of future and emerging translational opportunities for personalized, minimally invasive regenerative endodontic therapies.

Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative therapy for hematologic malignancies and bone marrow failure syndromes, yet outcomes remain highly heterogeneous and existing prognostic tools rely predominantly on pre-transplant clinical characteristics. We retrospectively analyzed 500 consecutive patients who underwent allogeneic HSCT at a single academic center between 2019 and 2025. Clinical characteristics, transplant variables, comorbidities, medication exposures, and longitudinal laboratory parameters were evaluated for associations with overall survival. Machine learning models incorporating dynamic post-transplant laboratory parameters demonstrated high performance in predicting overall survival compared to existing risk stratification techniques. Among evaluated predictors, early hematologic recovery emerged as one of the strongest determinants of long-term outcome. Specifically, achievement of a platelet count ≥90,000/μL by day +30 was independently associated with superior overall survival. These findings demonstrate that dynamic post-transplant laboratory data provide clinically meaningful prognostic information beyond traditional pre-transplant risk factors. Integration of early hematologic recovery metrics into machine learning-based prediction models may enable more accurate identification of high-risk patients and support individualized surveillance and management strategies following allogeneic HSCT.

Pluripotent adipose-derived stem cells (PASCs) are a non-tumorigenic, stress-enduring SSEA-3[+] cell population sharing key biological markers with Muse cells while representing a phenotypically distinct population. This Phase IIa randomized, double-blind, placebo-controlled pilot trial evaluated the safety, feasibility, and exploratory clinical effects of intravenous PASCs in Parkinson's disease (PD). Forty participants with Hoehn and Yahr stages I-III PD were randomized 1:1 to receive three intravenous infusions of PASCs (25 million cells) or placebo at baseline, month 3, and month 6, with 12-month follow-up. All participants underwent a structured neurological rehabilitation program. The primary endpoint was safety (CTCAE v5.0). No treatment-related adverse events of any grade were observed across 60 infusions. One thromboembolic event in the PASC group was independently adjudicated as of uncertain relationship to the study intervention, and one death in the placebo group was adjudicated as unrelated. For each of the seven exploratory functional and quality-of-life endpoints, the global treatment-by-time interaction was tested and adjusted for multiplicity using the Benjamini-Hochberg procedure; no endpoint reached significance after control of the false discovery rate (all q > 0.05). Repeated intravenous PASC administration is safe and feasible in PD. Efficacy was not demonstrated in this pilot trial, and the exploratory findings are hypothesis-generating, supporting further investigation in adequately powered Phase IIb/III trials.

Donor-specific antibodies (DSA) are preformed recipient antibodies directed against donor HLA antigens, most frequently observed in haploidentical or mismatched allogeneic hematopoietic cell transplantation (HCT). DSA assessed by multiplexed bead-based immunoassays at mean fluorescence intensity (MFI) values >1 000 are associated with increased risk of graft failure, graft-versus-host disease (GvHD), and mortality, supporting combined pharmacological and plasma-based depletion in absence of matching donors. We retrospectively analyzed all adult HCTs performed between 2009 and 2025 at the University Hospital Tübingen, Germany, with clinically relevant DSA (MFI >1 000). Assessments included depletion strategies, engraftment, GvHD, overall survival, and immune reconstitution. A 2:1 matched control cohort without DSA was selected based on disease, age, sex, and donor features. Fourteen cases were identified (1.2% of all transplants; 9.1% of haploidentical procedures). Depletion regimens included rituximab (n=12), bortezomib (n=10), daratumumab (n=2), intravenous immunoglobulins (n=6), plasma exchange (n=8), and immunoadsorption (n=9). MFI reduction <1 000 before HCT was achieved in 5 of 11 evaluable patients. All but two recipients engrafted timely; both graft failures occurred after single-modality depletion. Clinical outcomes did not differ significantly between DSA patients and controls. These real-world data underscore the importance of systematic DSA screening and multimodal depletion to optimize transplantation outcomes.

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.