Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson’s disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 ‘early-onset’ (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1–12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; χ² = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10–2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (χ² = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 – 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (χ² = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65–1.95; χ² = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1–12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD.

The high genetic diversity of HLA across populations significantly confines the effectiveness of a donor or umbilical cord blood search for allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to probe the HLA immunogenetic profile of the population of Crete, a Greek region with specific geographic and historical characteristics, and to investigate potential patterns in HLA distribution following comparison with the Deutsche Knochenmarkspenderdatei (DKMS) donor registry. It also aims to highlight the importance of regional public cord blood banks (PCBBs) in fulfilling HSCT needs, especially in countries with significant genetic diversity. A cohort of 1835 samples representative of the Cretan population was typed for HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, HLA-DQB1, HLA-DPB1) loci by high-resolution second field next-generation sequencing. Data were compared with the respective HLA profiles of 12 DKMS populations (n = 20 032). Advanced statistical and bioinformatics methods were employed to assess specific intra- and inter-population genetic indexes associated with the regional and geographic distribution of HLA alleles and haplotypes. A considerable HLA allelic and haplotypic diversity was identified among the Cretan samples and between the latter and the pooled DKMS cohort. Even though the HLA allele and haplotype frequency distribution was similar to regions of close geographic proximity to Crete, a clinal distribution pattern from the northern to southern regions was identified. Significant differences were also observed between Crete and the Greek population of DKMS. This study provides an in-depth characterization of the HLA immunogenetic profile in Crete and reveals the importance of demographic history in HLA heterogeneity and donor selection. The novel HLA allele and haplotype frequency comparative data between the Cretan and other European populations signify the importance of regional PCBBs in prioritizing HLA diversity to efficiently promote the HSCT program at the national level and beyond.

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system.

The review by Mazurek et al. summarizes the current strategies for generating megakaryocytes and functional platelets from iPSCs in vitro and outlines the developmental foundations of primitive and definitive hematopoiesis that underpin these efforts. Furthermore, they describe strategies aimed at improving maturation and yield, along with emerging approaches in HLA editing and immune tolerance, which are designed to overcome alloimmune barriers in transfusion medicine and regenerative therapies.The research paper by Alemany-Ribes et al. describes the generation of six iPSC lines as a model for investigating the molecular mechanisms underlying Multiple System Atrophy (MSA). Skin fibroblasts from patients with the two major MSA sub-types, MSA-P and MSA-C, with postmortem neuropathological confirmation in five cases, were reprogrammed into iPSC lines that fulfilled ISSCR quality standards and lacked acquired genetic abnormalities. Importantly, they differentiated into O4⁺ oligodendrocyte progenitor cells and MBP⁺ mature oligodendrocytes, providing a robust platform for studying MSA pathophysiology and therapeutic approaches.Within the context of modeling myeloid cell development, Tesakov et al. review the expanding applications of iPSC technology in hemato-oncology, highlighting its major advantages, current limitations and future therapeutic potential: the use of scalable iPSC-derived blood cell therapies for bone marrow failure syndromes and leukemia, and CRISPR-Cas9 genome editing to model defective hematopoiesis, elucidate disease mechanisms, and facilitate drug discovery and repurposing. To this end, they review the role of in silico screening platforms, e.g. L1000CDS2 and the Connectivity Map, in prioritizing candidate therapeutic markers and supporting preclinical validation.In their research article, Hutschalik et al. employed an iPSC-derived atrial tissue model to describe a novel inflammation-driven mechanism underlying atrial fibrillation (AF), the most common cardiac arrhythmia. Electrophysiological analyses demonstrated that M1 macrophage activation, combined with reduced expression of a series of AF associated markers, impaired electrical conduction and disrupted ion homeostasis. Computational tissue and whole-heart simulations confirmed that simultaneous reductions in sodium-potassium pump activity and tissue conductivity were sufficient to induce AF under tachycardic conditions even without ectopic activity, highlighting the value of combining iPSC models with in silico approaches to elucidate disease mechanisms and identify therapeutic targets.Challenges in iPSC applications: Despite significant advances, several challenges related to the risk of tumorigenicity due to genomic instability throughout reprogramming, long-term culture, lineage-specific differentiation and risk of residual undifferentiated cells are of concern for iPSC-based therapies.To this end, Requena et al. present the key features of the Altered Genome Induced Immune Response hypothesis of iPSCs, which postulates that reprogramming-associated genomic and epigenetic alterations may induce cell-type specific immunogenicity in iPSC-derived products. Chromosomal insertions and deletions together with epigenetic modifications could alter differentiation programs and generate immunogenic cell populations. This hypothesis may explain some previously reported immune responses with iPSC-derived cells, such as T cell infiltration in teratomas or unexpected immunogenicity of autologous iPSC-derived cardiomyocytes (iPSC-CMs).Within the same context, Kuebler et al. systematically evaluated the reprogramming efficiency of 150 iPSC lines by assessing the impact of donor characteristics, somatic cell source, culture conditions, reprogramming protocols, and passage numbers. Using diverse starting cell types, they minimized cell type-specific confounding effects. While technical parameters had only modest influence, donor-specific biological characteristics emerged as the primary determinants of reprogramming success, by affecting cell-cycle regulation, epigenetic remodeling, and responsiveness to reprogramming factors.The use of iPSCs lines from Human Leukocyte Antigen (HLA)-homozygous donors (i.e. haplo-lines) could be a mitigation strategy against the immunogenicity of iPSCs-derived transplants, especially during allogeneic regenerative cell therapies, since haplo-matching may profoundly expand the number of potential recipients.In the original research, Maeding et al. showed that HLA-homozygous iPSC-CMs exhibit a stable immune phenotype, comparable to that of HLA-heterozygous cells, based on single-cell spectral flow cytometric analysis of 54 immune and pluripotency markers. Although HLA-homozygous iPSC-CMs presented lower HLA-class I expression, compared to their heterozygous counterparts, they retained a robust response to inflammatory stimulation, with interferon-γ up-regulating HLA-Class I, HLA-E, HLA-F, PD-L1, PD-L2, and CD47. These findings support the development of HLA-homozygous iPSC-CMs as semi-universal donor cells and establish spectral flow cytometry as a valuable platform for immune monitoring in cardiac cell replacement therapy.