Transplantation of Human Embryonic Stem Cell-Derived Pericyte-Like Cells Transduced with Basic Fibroblast Growth Factor Promotes Angiogenic Recovery in Mice with Severe Chronic Hindlimb Ischemia.

Critical limb ischemia (CLI) is a state of severe peripheral artery disease, with no effective treatment. Cell therapy has been investigated as a therapeutic tool for CLI, and pericytes are promising therapeutic candidates based on their angiogenic properties. We firstly generated highly proliferative and immunosuppressive pericyte-like cells from embryonic stem (ES) cells.

Remote audit practice for inspection of structural and equipment standards for cell processing facilities under the act on the safety of regenerative medicine in Japan.

Introduction: The Act on the Safety of Regenerative Medicine enforced in Japan in 2014, regulates the manufacture of cellular processed products. However, with regards to the manufacturing facilities at medical institutions, only the submission of necessary documents is required for a license, and the need for third-party inspection has been highlighted. Remote activities are becoming more prominent with the spread of the Severe Acute Respiratory Syndrome Coronavirus 2 infection; therefore, the current assessment of compliance with structural facility standards was conducted remotely.

Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports.

Introduction: With the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies.

Study Design: The inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.

Add-On Effect of Hemagglutinating Virus of Japan Envelope Combined with Chemotherapy or Immune Checkpoint Inhibitor against Malignant Pleural Mesothelioma: An In Vivo Study.

Malignant pleural mesothelioma (MPM) is a refractory tumor because most of the lesions are already disseminated at diagnosis. Previously, the main treatment for MPM was combination chemotherapy. However, recently, immune checkpoint inhibitors (ICIs) are also used.

Case report: Transplantation of human induced pluripotent stem cell-derived cardiomyocyte patches for ischemic cardiomyopathy.

Despite major therapeutic advances, heart failure, as a non-communicable disease, remains a life-threatening disorder, with 26 million patients worldwide, causing more deaths than cancer. Therefore, novel strategies for the treatment of heart failure continue to be an important clinical need. Based on preclinical studies, allogenic human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) patches have been proposed as a potential therapeutic candidate for heart failure.

Engineered three-dimensional cardiac tissues maturing in a rotating wall vessel bioreactor remodel diseased hearts in rats with myocardial infarction.

A rotating wall vessel (RWV) bioreactor was constructed for growing massive functional cardiac constructs to recover the function of a distressed rat heart. Three-dimensional cardiac tissues were engineered by seeding human-induced pluripotent stem cell-derived cardiomyocytes on poly(lactic-co-glycolic acid) fiber sheets (3D-hiPSC-CTs) and cultured in the RWV bioreactor (RWV group) or under static conditions (control group). The tissues were transplanted into a myocardial infarction nude rat model, and cardiac performance was evaluated.

Non-Woven Sheet Containing Gemcitabine: Controlled Release Complex for Pancreatic Cancer Treatment.

The 5-year survival rate for pancreatic cancer remains low, and the development of new methods for its treatment is actively underway. After the surgical treatment of pancreatic cancer, recurrence and peritoneal dissemination can be prevented by long-term local exposure to appropriate drug concentrations. We propose a novel treatment method using non-woven sheets to achieve this goal.

Rapid and sensitive mycoplasma detection system using image-based deep learning.

A major concern in the clinical application of cell therapy is the manufacturing cost of cell products, which mainly depends on quality control. The mycoplasma test, an important biological test in cell therapy, takes several weeks to detect a microorganism and is extremely expensive. Furthermore, the manual detection of mycoplasma from images requires high-level expertise.

A Novel Formulation of Cisplatin with γ-Polyglutamic Acid and Chitosan Reduces Its Adverse Renal Effects: An In Vitro and In Vivo Animal Study.

Cisplatin (-diamminedichloroplatinum (II); CDDP) is a key chemotherapeutic agent but causes renal damage and other off-target effects. Here, we describe the pharmacological and biochemical characteristics of a novel formulation of CDDP complexed with γ-polyglutamic acid (γ-PGA) and chitosan (CS), γ-PGA/CDDP-CS, developed by complexing CDDP with γ-PGA, then adding CS (15 kDa; 10 mol%/γ-PGA). We analyzed tumor cytotoxicity in vitro, as well as blood kinetics, acute toxicity, and antitumor efficacy in vivo in BALB/cAJcl mice.

A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates.

Critical limb ischemia (CLI) is a severe state of peripheral artery disease with high unmet clinical needs. Further, there are no effective treatment options for patients with CLI. Based on preclinical study results, predicting the clinical efficacy of CLI treatments is typically difficult because conventional hindlimb ischemia (HLI) rodent models display spontaneous recovery from ischemia, which is not observed in patients with CLI.

Novel Hyaluronan Formulation Enhances the Efficacy of Boron Neutron Capture Therapy for Murine Mesothelioma.

Background: Malignant pleural mesothelioma (MPM) is a refractory cancer of the pleura caused by asbestos exposure. MPM is difficult to treat because it easily disseminates. Boron neutron capture therapy (BNCT) is a radiotherapy in which cancer cells that selectively take up (10)Boron-containing compounds are destroyed, and normal cells are uninjured.

Nano-decoration of the Hemagglutinating Virus of Japan envelope (HVJ-E) using a layer-by-layer assembly technique.

In this study, we created a nanoscale layer of hyaluronic acid (HA) on the inactivated Hemagglutinating Virus of Japan envelope (HVJ-E) via a layer-by-layer (LbL) assembly technique for CD-44 targeted delivery. HVJ-E was selected as the template virus because it has shown a tumor-suppressing ability by eliciting inflammatory cytokine production in dendritic cells. Although it has been required to increase the tumor-targeting ability and reduce nonspecific binding because HVJ-E fuses with virtually all cells and induces hemagglutination in the bloodstream, complete modifications of single-envelope-type viruses with HA have been difficult.

Biosurfactant mannosyl-erythritol lipid inhibits secretion of inflammatory mediators from RBL-2H3 cells.

Background: Biosurfactant mannosyl-erythritol lipids (MELs) are glycolipids produced by microbes that have various biological activities. It has been reported that MELs exhibit excellent surface-activity and also various bioactivities, such as induction of cell differentiation and apoptosis. However, little is known about their action related to drug discovery or drug seeds.

Cationized gelatin-HVJ envelope with sodium borocaptate improved the BNCT efficacy for liver tumors in vivo.

Background: Boron neutron capture therapy (BNCT) is a cell-selective radiation therapy that uses the alpha particles and lithium nuclei produced by the boron neutron capture reaction. BNCT is a relatively safe tool for treating multiple or diffuse malignant tumors with little injury to normal tissue. The success or failure of BNCT depends upon the 10B compound accumulation within tumor cells and the proximity of the tumor cells to the body surface.

Artificial exocytotic system that secretes intravesicular contents upon Ca2+ influx.

Exocytosis is a crucial process of secreting various signaling molecules such as neurotransmitters, hormones, and other chemical mediators into the extracellular space. Exocytotic release is caused by membrane fusion of intracellular vesicles with the plasma membrane triggered by an increase in intracellular Ca(2+). In the present study, we developed an artificial system of exocytosis that secretes intravesicular contents upon Ca(2+) influx.