Acceptance of Murine Islet Allografts Without Immunosuppression in Inguinal Subcutaneous White Adipose Tissue Pretreated With bFGF.

Prevention of immune rejection without immunosuppression is the ultimate goal of transplant immunobiology. One way to achieve this in cellular transplantation, such as with islet transplantation, is to create a favorable local environment at the transplant site. In the current study, we found that C57BL/6 mice with streptozotocin-induced diabetes remained normoglycemic for >1 year after transplantation of BALB/c islets without immunosuppression when the inguinal subcutaneous white adipose tissue (ISWAT) was the site of transplantation and when the site was pretreated with basic fibroblast growth factor.

Dual-phase Au-Pt alloys free from magnetic susceptibility artifacts in magnetic resonance imaging.

Purpose: Magnetic resonance imaging (MRI) devices are frequently used in image-based diagnosis. In the case of large artifacts, which are generated in magnetic resonance (MR) images when magnetic materials, such as metals, are present in the body, these devices are less useful. This study aimed to develop a dual-phase Au-Pt alloy that does not generate artifacts in MR images and has high workability to prepare medical devices.

A Novel Human Placental Barrier Model Based on Trophoblast Stem Cells Derived from Human Induced Pluripotent Stem Cells.

The placenta acts as an interface between the fetus and the expecting mother. Various drugs and environmental pollutants can pass through the human placental barrier and may harm the developing fetus. Currently available placental barrier models are often inadequate, because they are lacking the functional trophoblast cells.

Three-Dimensional Cell Sheet Construction Method with a Polyester Micromesh Sheet.

Cell sheet engineering has become important in a variety of fields, including regenerative medicine and transplantation. Our research group previously developed micromesh cultures that enable cells to form a cell sheet on a microstructured mesh sheet. Here, we present a more usable micromesh culture and devices that make it possible, aiming for widespread use.

A comparative study of key physiological stem cell parameters between three human trophoblast cell lines.

Human trophoblast stem cells (TSCs) play a key role in the placenta. These cells are proliferative, undifferentiated, and can differentiate into mature trophoblast cell types. However, primary human TSCs are difficult to obtain.

Induction of Ectopic Hematopoiesis by a Three-Dimensional Structured Extracellular Matrix Derived from Decellularized Cancellous Bone.

An blood production system could be an alternative to blood donation. We constructed a hematopoietic microenvironment using decellularized cancellous bones (DCBs) as scaffolds to sustain hematopoietic stem cells and supporting cells. The subcutaneous implantation of DCBs into mice with or without human mesenchymal stem cells (hMSCs) revealed that regardless of the presence of hMSCs DCBs were recellularized by some host cells and induced hematopoiesis.

Compact fluidic system for functional assessment of pancreatic islets.

Transplantation of pancreatic islets is becoming a promising therapy for people with type I diabetes. In this study, we present a compact fluidic system that enables assessment of islet functionality ex vivo for efficient islet transplantation. The fluidic system includes a micromesh sheet-embedded chip.

Tuning intercellular adhesion with membrane-anchored oligonucleotides.

Adhesive interactions between cells play an integral role in development, differentiation and regeneration. Existing methods for controlling cell-cell cohesion and adhesion by manipulating protein expression are constrained by biological interdependencies, e.g.

Establishment of human trophoblast stem cells from human induced pluripotent stem cell-derived cystic cells under micromesh culture.

Background: Trophoblasts as a specific cell lineage are crucial for the correct function of the placenta. Human trophoblast stem cells (hTSCs) are a proliferative population that can differentiate into syncytiotrophoblasts and extravillous cytotrophoblasts. Many studies have reported that chemical supplements induce the differentiation of trophoblasts from human induced pluripotent stem cells (hiPSCs).

Chemically defined conditions for long-term maintenance of pancreatic progenitors derived from human induced pluripotent stem cells.

Large numbers of hormone-releasing cells, approximately 10 endocrine cells, are required to treat type I diabetes patients by cell transplantation. The SOX9-positive pancreatic epithelium proliferates extensively during the early stages of pancreatic development. SOX9-positive pancreatic epithelium is thought to be an expandable cell source of β cells for transplantation therapy.

Development of trophoblast cystic structures from human induced pluripotent stem cells in limited-area cell culture.

We developed a novel engineering technique to induce differentiation of human induced pluripotent stem cells (hiPSCs) into organoids mimicking the trophectoderm (TE). Here, hiPSCs were cultured on a limited area of 2-4 mm in diameter. After 15-20 days, spherical cysts appeared on the surface of the limited area.

Preparation of Immunotolerant Space Under the Skin and Transplantation of Islets in the Space.

Although transplantation of islets of Langerhans has been accepted as a fundamental treatment for insulin-dependent diabetes mellitus (IDDM), several problems are still remaining in order that it becomes the standard medical treatment of IDDM patients. In this study, using diabetic rat models, a subcutaneous space surrounded with highly vascularized granulomatous tissue was formed by agarose-bFGF rod implantation. Allogeneic islets transplanted into the space could survive and release insulin for a long period under no immunosuppressive medication.

Bioabsorbable device to prepare subcutaneous pockets for islet transplantation.

Small invasive transplantation of islets and long maintenance of the islet graft without immunosuppression has been studied for the treatment of type 1 diabetes. Clinically, subcutaneous pockets surrounding vascular-rich tissue are prepared for islet transplantation using a device made of the materials. Here, gelatin sheets were implanted into two dorsal subcutaneous sites in diabetic ACI rats, and a mixture of bFGF and sodium hyaluronate solution was injected around the gelatin sheets.

Design of Bioartificial Pancreases From the Standpoint of Oxygen Supply.

A bioartificial pancreas (BAP), in which islets of Langerhans (islets) are enclosed in a semipermeable membrane, has been developed to realize islet transplantation without the use of immunosuppressive drugs. Although recent progress in induced pluripotent stem (iPS) and embryonic stem (ES) cells has attracted attention owing to the potential applications of these cells as insulin-releasing cells, concerns about the safety of implantation of these cells remain. The use of the BAP has the advantage of easy removal if insulin-releasing cells derived from iPS/ES cells undesirably proliferate and form tumors in the BAP.

Long-term Functioning of Allogeneic Islets in Subcutaneous Tissue Pretreated With a Novel Cyclic Peptide Without Immunosuppressive Medication.

Background: There exists a need for a minimally invasive method of islet transplantation without immunosuppressive drugs for the treatment of type 1 diabetes.

Methods: In diabetic August Copenhagen Irish rats, an agarose rod containing the cyclic oligopeptide SEK-1005 (agarose-SEK rod) was implanted at 2 dorsal subcutaneous sites. Then these rods were removed, and 1500 islets of Langerhans isolated from Fischer 344 rats were transplanted into each of the pockets.

Evaluation of the Perceptual Characteristics of a Force Induced by Asymmetric Vibrations.

This paper describes the perceptual characteristics of a sense of a force induced by asymmetric vibration using a vibration speaker-type non-grounded haptic interface. We confirm that the vibration speaker generates a perceived force that pulls or pushes a user's hand in a particular direction when an asymmetric amplitude signal that is generated by inverting a part of a sine wave is input. In this paper, to verify the system with respect to various factors of force perception caused by asymmetric vibration, we conducted six experiments and the following results were obtained.

Encountered-Type Haptic Interface for Representation of Shape and Rigidity of 3D Virtual Objects.

This paper describes the development of an encountered-type haptic interface that can generate the physical characteristics, such as shape and rigidity, of three-dimensional (3D) virtual objects using an array of newly developed non-expandable balloons. To alter the rigidity of each non-expandable balloon, the volume of air in it is controlled through a linear actuator and a pressure sensor based on Hooke's law. Furthermore, to change the volume of each balloon, its exposed surface area is controlled by using another linear actuator with a trumpet-shaped tube.

Preparation of an Au-Pt alloy free from artifacts in magnetic resonance imaging.

Purpose: When magnetic resonance imaging (MRI) is performed on patients carrying metallic implants, artifacts can disturb the images around the implants, often making it difficult to interpret them appropriately. However, metallic materials are and will be indispensable as raw materials for medical devices because of their electric conductivity, visibility under X-ray fluoroscopy, and other favorable features. What is now desired is to develop a metallic material which causes no artifacts during MRI.

Closed-channel culture system for efficient and reproducible differentiation of human pluripotent stem cells into islet cells.

Human pluripotent stem cells (hPSCs) are thought to be a promising cell-source solution for regenerative medicine due to their indefinite proliferative potential and ability to differentiate to functional somatic cells. However, issues remain with regard to achieving reproducible differentiation of cells with the required functionality for realizing human transplantation therapies and with regard to reducing the potential for bacterial or fungal contamination. To meet these needs, we have developed a closed-channel culture device and corresponding control system.

Interaction of poly(ethylene glycol)-conjugated phospholipids with supported lipid membranes and their influence on protein adsorption.

We studied real-time interaction between poly(ethylene glycol)-conjugated phospholipids (PEG-lipids) and a supported lipid membrane by surface plasmon resonance (SPR) spectroscopy to understand dynamic behaviors of PEG-lipids on living cell membranes. Supported lipid membranes formed on a hydrophobic surface were employed as a model of living cell membrane. We prepared three kinds of PEG-lipids that carried alkyl chains of different lengths for SPR measurements and also performed fluorescence recovery after photobleaching (FRAP) to study the influence of acyl chain length on dynamics on the supported membrane.

Reproducible preparation of spheroids of pancreatic hormone positive cells from human iPS cells: An in vitro study.

Background: Transplantation of islets of Langerhans is regarded as a promising therapy for type 1 diabetes. A large number of β-cells are required for the treatment of human type 1 diabetes. Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, have been considered as new sources for cell replacement therapy.

Long-term maintenance of human induced pluripotent stem cells by automated cell culture system.

Pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem (iPS) cells, are regarded as new sources for cell replacement therapy. These cells can unlimitedly expand under undifferentiated conditions and be differentiated into multiple cell types. Automated culture systems enable the large-scale production of cells.

Interaction between cells and poly(ethylene glycol)-lipid conjugates.

Eight types of poly(ethylene glycol)-lipid(PEG-lipids) carrying different lipid tails were synthesized. These PEG-lipids were labeled with fluorescein isothiocyanate (FITC-PEG-lipids) to examine their interaction with cells and to quantitatively determine amounts of PEG-lipids bound on the cell surface. FITC-PEG-lipids spontaneously anchored to the cell membrane within 15 min without loss of cell viability.

Preferential adsorption of cell adhesive proteins from complex media on self-assembled monolayers and its effect on subsequent cell adhesion.

Unlabelled: We examined the effect of surface chemistry on adsorption of fibronectin (Fn) and vitronectin (Vn) and subsequent cell adhesion, employing self-assembled monolayers (SAMs) of alkanethiols carrying terminal methyl (CH3), hydroxyl groups (OH), carboxylic acid (COOH), and amine (NH2). More Fn and Vn adsorbed to COOH- and NH2-SAMs than to CH3- and OH-SAMs from a mixture with bovine serum albumin (BSA) and from 2% fetal bovine serum. Adhesion of human umbilical vein endothelial cells (HUVECs) on CH3- and OH-SAMs preadsorbed with Fn and BSA decreased with decreasing adsorbed Fn; however, HUVECs adhered to COOH- and NH2-SAMs even in the presence of BSA at 1000-fold more than Fn in a mixture because of the preferential adsorption of Fn and/or displacement of preadsorbed BSA with Fn and Vn in a serum-containing medium.

Maturation of human iPS cell-derived dopamine neuron precursors in alginate-Ca(2+) hydrogel.

Background: Pluripotent stem cells (embryonic stem/induced pluripotent stem cells) have been widely studied as a potential cell source for cell transplantation therapy of Parkinson's disease. However, some difficulties remain to be overcome. These include the need to prepare a large number of dopamine (DA) neurons for clinical use and to culture the cells for a long period to allow their functional maturation and the removal of undifferentiated cells.