Impact of the COVID-19 outbreak on the field of hematopoietic cell transplantation in the Asia-Pacific region: APBMT Activity Survey 2020/2021.

COVID-19 became a global pandemic in 2020 and significantly affected the activity of hematopoietic cell transplants (HCT) worldwide. Despite these challenges, a total of 28,793 transplants, including 18,518 allogeneic and 10,275 autologous transplants, were performed in 719 facilities in 2020 in the Asia-Pacific (AP) region. This represented a 5.

Betibeglogene autotemcel gene therapy in patients with transfusion-dependent, severe genotype β-thalassaemia (HGB-212): a non-randomised, multicentre, single-arm, open-label, single-dose, phase 3 trial.

Background: Transfusion-dependent β-thalassaemia (TDT) is a severe disease, resulting in lifelong blood transfusions, iron overload, and associated complications. Betibeglogene autotemcel (beti-cel) gene therapy uses autologous haematopoietic stem and progenitor cells (HSPCs) transduced with BB305 lentiviral vector to enable transfusion independence.

Methods: HGB-212 was a non-randomised, multicentre, single-arm, open-label, phase 3 study of beti-cel in patients with TDT conducted at eight centres in France, Germany, Greece, Italy, the UK, and the USA.

GDNF and cAMP significantly enhance blood-brain barrier integrity in a humanized tricellular transwell model.

Blood-brain barrier (BBB) is a crucial membrane safeguarding neural tissue by controlling the molecular exchange between blood and the brain. However, assessing BBB permeability presents challenges for central nervous system (CNS) drug development. studies of BBB-permeable agents before animal testing are essential to mitigate failures.

Disturbance of Immune Microenvironment in Androgenetic Alopecia through Spatial Transcriptomics.

Androgenetic alopecia (AGA) is characterized by microinflammation and abnormal immune responses, particularly in the upper segment of hair follicles (HFs). However, the precise patterns of immune dysregulation remain unclear, partly due to limitations in current analysis techniques to preserve tissue architecture. The infundibulum, a major part of the upper segment of HFs, is associated with significant clusters of immune cells.

Generation of integration-free human induced pluripotent stem cell line MURAi003-A derived from the peripheral blood mononuclear cells of a donor with homozygous Class I and Class II HLAs (A*11:01, B*46:01; C*01:02; DRB1*09:01; DQB1*03:03).

The human leukocyte antigen (HLA) system comprises cell-surface proteins responsible for the presentation of peptide antigens. HLAs play an essential role in the regulation of the human immune system, and their studies have been crucial to its understanding. To create a sustainable model for the investigation of HLAs, we successfully generated the human iPSC line MURAi003-A derived from the peripheral blood mononuclear cells of a donor with homozygous Class I and Class II HLAs (A*11:01, B*46:01; C*01:02; DRB1*09:01; DQB1*03:03) using non-integrative reprogramming episomes.

Establishment of human induced pluripotent stem cell line MURAi001-A from skin fibroblasts of a patient carrying a c.4404A > G mutation in the TET1 gene.

Ten-Eleven Translocation methylcytosine dioxygenase 1 (TET1) is known to play a broad tumor suppressor role through demethylating and activating tumor suppressor genes. TET1 missense mutations are previously reported in many types of leukemia. Here, the human induced pluripotent stem cell line MURAi001-A was generated from skin fibroblasts derived from a 56-year-old female patient carrying the TET1 gene mutation c.

Investigating the impact of botulinum toxin type a on the migration of normal human dermal fibroblasts: An in vitro wound healing assay.

Background: Botulinum toxin A (BoNT-A) is widely utilized in the management of hypertrophic and keloid scars. One proposed mechanism for scar prevention involves the inhibition of fibroblast migration in scars by BoNT-A. However, the data regarding the effect of BoNT-A on the migration of normal human dermal fibroblasts (NHDF) is limited.

Development of red blood cell-derived extracellular particles as a biocompatible nanocarrier of microRNA-204 (REP-204) to harness anti-neuroblastoma effect.

Neuroblastoma (NB) is the most common extracranial solid tumor in the pediatric population with a high degree of heterogeneity in clinical outcomes. Upregulation of the tumor suppressor miR-204 in neuroblastoma is associated with good prognosis. Although miR-204 has been recognized as a potential therapeutic candidate, its delivery is unavailable.

Targeting pediatric solid tumors in the new era of RNA therapeutics.

Despite substantial progress in pediatric cancer treatment, poor prognosis remained for patients with recurrent or metastatic disease, given the limitations of approved targeted treatments and immunotherapies. RNA therapeutics offer significant potential for addressing a broad spectrum of diseases, including cancer. Advances in manufacturing and delivery systems are paving the way for the rapid development of therapeutic RNAs for clinical applications.

Model-Informed Precision Dosing of Intravenous Busulfan in Thai Pediatrics Undergoing Hematopoietic Stem Cell Transplantation.

Background: Conditioning bifunctional agent, busulfan, is commonly used on children before hematopoietic stem cell transplantation. Currently, at the Ramathibodi hospital, Bangkok, Thailand, initial dosing is calculated according to age and body surface area, and 7 samples per day are used for therapeutic drug monitoring (TDM). This study aimed to identify the best strategies for individual dosages a priori from patient characteristics and a posteriori based on TDM.

CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for cellular resistant to R5 and X4 tropic HIV-1.

Hematopoietic stem-cell (HSC) transplantation using a donor with a homozygous mutation in the HIV co-receptor CCR5 (CCR5Δ32/Δ32) holds great promise as a cure for HIV-1. Previously, there were three patients that had been reported to be completely cured from HIV infection by this approach. However, finding a naturally suitable Human Leukocyte Antigen (HLA)-matched homozygous CCR5Δ32 donor is very difficult.

Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection.

More than 58 million individuals worldwide are inflicted with chronic HCV. The disease carries a high risk of end stage liver disease, i.e.

Extracellular Vesicles for Childhood Cancer Liquid Biopsy.

Liquid biopsy involves the utilization of minimally invasive or noninvasive techniques to detect biomarkers in biofluids for disease diagnosis, monitoring, or guiding treatments. This approach is promising for the early diagnosis of childhood cancer, especially for brain tumors, where tissue biopsies are more challenging and cause late detection. Extracellular vesicles offer several characteristics that make them ideal resources for childhood cancer liquid biopsy.

The translational gap for gene therapies in low- and middle-income countries.

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical scope of gene therapies expands, consideration must be given to those who will benefit and what proactive steps must be taken to widen development and access potential, particularly in regions carrying a high disease burden.

An increase in ER stress and unfolded protein response in iPSCs-derived neuronal cells from neuronopathic Gaucher disease patients.

Gaucher disease (GD) is a lysosomal storage disorder caused by a mutation in the GBA1 gene, responsible for encoding the enzyme Glucocerebrosidase (GCase). Although neuronal death and neuroinflammation have been observed in the brains of individuals with neuronopathic Gaucher disease (nGD), the exact mechanism underlying neurodegeneration in nGD remains unclear. In this study, we used two induced pluripotent stem cells (iPSCs)-derived neuronal cell lines acquired from two type-3 GD patients (GD3-1 and GD3-2) to investigate the mechanisms underlying nGD by biochemical analyses.

Droplet digital polymerase chain reaction-based quantitation of therapeutic lentiviral vector copies in transduced hematopoietic stem cells.

Background Aims: Gene therapy using lentiviral vectors (LVs) that harbor a functional β-globin gene provides a curative treatment for hemoglobinopathies including beta-thalassemia and sickle cell disease. Accurate quantification of the vector copy number (VCN) and/or the proportion of transduced cells is critical to evaluate the efficacy of transduction and stability of the transgene during treatment. Moreover, commonly used techniques for LV quantification, including real-time quantitative polymerase chain reaction (PCR) or fluorescence-activated cell sorting, require either a standard curve or expression of a reporter protein for the detection of transduced cells.

HIV-1 proviral DNA in purified peripheral blood CD34 stem and progenitor cells in individuals with long-term HAART; paving the way to HIV gene therapy.

Human immunodeficiency virus (HIV)-1 infection is an important public health problem worldwide. After primary HIV-1 infection, transcribed HIV-1 DNA is integrated into the host genome, serving as a reservoir of the virus and hindering a definite cure. Although highly active antiretroviral therapy suppresses active viral replication, resulting in undetectable levels of HIV RNA in the blood, a viral rebound can be detected after a few weeks of treatment interruption.

Unveiling the Antiviral Properties of Panduratin A through SARS-CoV-2 Infection Modeling in Cardiomyocytes.

Establishing a drug-screening platform is critical for the discovery of potential antiviral agents against SARS-CoV-2. In this study, we developed a platform based on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to investigate SARS-CoV-2 infectivity, with the aim of evaluating potential antiviral agents for anti-SARS-CoV-2 activity and cardiotoxicity. Cultured myocytes of iPSC-CMs and immortalized human cardiomyocyte cell line (AC-16) were primarily characterized for the expression of cardiac markers and host receptors of SARS-CoV-2.