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.
Background To 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. Methods In 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. Results No 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. Conclusions Although 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.
