A report of the 17th congress of the Japanese Society for Regenerative Medicine.

The 17th Congress of the Japanese Society for Regenerative Medicine was held on March 21-23, 2018 at PACIFICO Yokohama (Kanagawa Prefecture) with 3860 participants. The theme of the congress was 'The Integration of Wisdom from All Sectors.' With this theme, this congress aimed to provide people from all sectors (including individuals from various industries, regulatory authorities, academia, and citizens) with opportunities for exchanging views on regenerative medicine under one roof.

An inducible knockout of Dicer in adult mice does not affect endurance exercise-induced muscle adaptation.

The contractile and metabolic properties of adult skeletal muscle change in response to endurance exercise. The mechanisms of transcriptional regulation in exercise-induced skeletal muscle adaptation, including fiber-type switching and mitochondrial biogenesis, have been investigated intensively, whereas the role of microRNA (miRNA)-mediated posttranscriptional gene regulation is less well understood. We used tamoxifen-inducible Dicer1 knockout (iDicer KO) mice to reduce the global expression of miRNAs in adult skeletal muscle and subjected these mice to 2 wk of voluntary wheel running.

AIM-deficient mouse fed a high-trans fat, high-cholesterol diet: a new animal model for nonalcoholic fatty liver disease.

Owing to changes in lifestyle, nonalcoholic fatty liver disease (NAFLD) is becoming a common form of chronic liver injury. NAFLD comprises a wide variety of disease stages, from simple steatosis to nonalcoholic steatohepatitis, which is a risk factor for the development of hepatocellular carcinoma (HCC). Because animal models for NAFLD are needed to investigate the precise pathogenesis, we aimed to establish a new mouse model employing mice deficient for apoptosis inhibitor of macrophage (AIM), which exhibit accelerated lipid storage in the liver and high susceptibility to developing HCC in response to a high-fat diet (HFD).

Strong stimulation triggers full fusion exocytosis and very slow endocytosis of the small dense core granules in carotid glomus cells.

Chemosensory glomus cells of the carotid bodies release transmitters, including ATP and dopamine mainly via the exocytosis of small dense core granules (SDCGs, vesicular diameter of ∼100 nm). Using carbon-fiber amperometry, we showed previously that with a modest uniform elevation in cytosolic Ca concentration ([Ca] of ∼0.5 µM), SDCGs of rat glomus cells predominantly underwent a "kiss-and-run" mode of exocytosis.

Somatic role of SYCE2: an insulator that dissociates HP1α from H3K9me3 and potentiates DNA repair.

The synaptonemal complex is a proteinaceous structure essential for meiotic recombination, and its components have been assumed to play a role exclusively in the germ line. However, SYCE2, a component constituting the synaptonemal complex, is expressed at varying levels in somatic cells. Considering its potent protein-binding activities, it may be possible that SYCE2 plays a somatic role by affecting nuclear functions.

Volume Dynamics of Dendritic Spines in the Neocortex of Wild-Type and KO Mice.

Excitatory synapses are often formed at small protrusions of dendrite, called dendritic spines, in most projection neurons, and the spine-head volumes show strong correlations with synaptic connectivity. We examined the dynamics of spine volume in the adult mouse visual cortex using time-lapse two-photon imaging with a resonant Galvano scanner. Contrary to expectations, we found that the spines in the adult neocortex showed fluctuations to a similar degree as that observed in young hippocampal preparations, but there were systematic differences in how the dynamics were dependent on spine volumes, thus allowing for fewer fluctuations in small spines, which could account for the relatively low turnover rates of neocortical spines .

The IgM pentamer is an asymmetric pentagon with an open groove that binds the AIM protein.

Soluble immunoglobulin M (IgM) forms a pentamer containing a joining (J) chain polypeptide. While IgM pentamer has various immune functions, it also behaves as a carrier of circulating apoptosis inhibitor of macrophage (AIM; also called CD5L) protein that facilitates repair during different diseases. AIM binds to the IgM pentamer solely in the presence of the J chain.

Generation of orthotopically functional salivary gland from embryonic stem cells.

Organoids generated from pluripotent stem cells are used in the development of organ replacement regenerative therapy by recapitulating the process of organogenesis. These processes are strictly regulated by morphogen signalling and transcriptional networks. However, the precise transcription factors involved in the organogenesis of exocrine glands, including salivary glands, remain unknown.

The role of PNPLA1 in ω-O-acylceramide synthesis and skin barrier function.

The human genome encodes nine enzymes belonging to the patatin-like phospholipase domain-containing lipase (PNPLA)/Ca-independent phospholipase A (iPLA) family. Although most PNPLA/iPLA enzymes are widely distributed and act on phospholipids or neutral lipids as (phospho)lipases to play homeostatic roles in lipid metabolism, the function of PNPLA1 remained a mystery until a few years ago. However, the recent finding that mutations in the human PNPLA1 gene are linked to autosomal recessive congenital ichthyosis (ARCI), as well as evidence obtained from biochemical and gene knockout studies, has shed light on the function of this enzyme in skin-specific sphingolipid metabolism rather than glycerophospholipid metabolism.

Bone regeneration by calcium phosphate-loaded carboxymethyl cellulose nonwoven sheets in canine femoral condyle defects.

The bone regeneration capacities of calcium phosphate (CaP)-loaded carboxymethyl cellulose (CMC) nonwoven sheet (CMC/CaP) were evaluated using a dog lateral femoral condyle defect model. In addition, the effect of bFGF on bone regeneration when added to CMC/CaP sheet was investigated. The CMC and CMC/CaP sheets have high operability.

Human Rad52 Promotes XPG-Mediated R-loop Processing to Initiate Transcription-Associated Homologous Recombination Repair.

Given that genomic DNA exerts its function by being transcribed, it is critical for the maintenance of homeostasis that DNA damage, such as double-strand breaks (DSBs), within transcriptionally active regions undergoes accurate repair. However, it remains unclear how this is achieved. Here, we describe a mechanism for transcription-associated homologous recombination repair (TA-HRR) in human cells.

Prevention of Peritoneal Adhesions by Ferric Ion-Cross-Linked Hydrogels of Hyaluronic Acid Modified with Iminodiacetic Acids.

We fabricated ferric ion-cross-linked hydrogels of a chelating hyaluronic acid (HA) derivative. HA was conjugated with iminodiacetic acid (IDA) at 22% of a modification degree to its disaccharide unit of HA. This conjugate (HA-IDA) showed degradability by hyaluronidase even after the IDA modification, and its degradation rate was almost the same as that of HA.

mGlu1 Receptors Monopolize the Synaptic Control of Cerebellar Purkinje Cells by Epigenetically Down-Regulating mGlu5 Receptors.

In cerebellar Purkinje cells (PCs) type-1 metabotropic glutamate (mGlu1) receptors play a key role in motor learning and drive the refinement of synaptic innervation during postnatal development. The cognate mGlu5 receptor is absent in mature PCs and shows low expression levels in the adult cerebellar cortex. Here we found that mGlu5 receptors were heavily expressed by PCs in the early postnatal life, when mGlu1α receptors were barely detectable.

Independent modes of disease repair by AIM protein distinguished in AIM-felinized mice.

Tissue macrophage-derived apoptosis inhibitor of macrophage (AIM, encoded by cd5l gene) is a circulating protein that has suppressive functions in a broad range of diseases including obesity, liver steatosis, hepatocellular carcinoma (HCC), and acute kidney injury (AKI). In healthy states, high levels of AIM circulate in the inactivated state by associating with the immunoglobulin M (IgM) pentamer in the blood, whereas during AKI, AIM dissociates from IgM and gains disease repair activity. Here, we assessed whether AIM activation via its release from IgM is required to ameliorate other diseases.

Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents.

We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification.

Higher visual responses in the temporal cortex of mice.

The visual cortex of mice is a useful model for investigating the mammalian visual system. In primates, higher visual areas are classified into two parts, the dorsal stream ("where" pathway) and ventral stream ("what" pathway). The ventral stream is known to include a part of the temporal cortex.

Treatment of Bone Defects by Transplantation of Genetically Modified Mesenchymal Stem Cell Spheroids.

Cell transplantation is promising for regenerative medicine. A combination of a three-dimensional spheroid culture system with gene transfection was developed to enhance the therapeutic effects of mesenchymal stem cell (MSC) transplantation. The spheroid cell culture system is based on micropatterned substrates composed of a regular array of 100-μm-diameter cell-adhesion areas coated with a temperature-responsive polymer, poly (N-isopropylacrylamide-co-methacrylic acid), which allows for spheroid detachment by simply cooling the plates.

Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis.

DDHD2/KIAA0725p is a mammalian intracellular phospholipase A that exhibits phospholipase and lipase activities. Mutation of the DDHD2 gene causes hereditary spastic paraplegia (SPG54), an inherited neurological disorder characterized by lower limb spasticity and weakness. Although previous studies demonstrated lipid droplet accumulation in the brains of SPG54 patients and DDHD2 knockout mice, the cause of SPG54 remains elusive.

Five-week yin yoga-based interventions decreased plasma adrenomedullin and increased psychological health in stressed adults: A randomized controlled trial.

Background: Non-communicable diseases (NCDs, e.g. cardiovascular disease) are responsible for high rates of morbidity and the majority of premature deaths worldwide.

Prognostic factors of Erdheim-Chester disease: a nationwide survey in Japan.

Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11).

The adhesion molecule cadherin 11 is essential for acquisition of normal hearing ability through middle ear development in the mouse.

Cadherin 11 (Cdh11), a member of the cadherin adhesion molecule family, is expressed in various regions of the brain as well as the head and ear. To gain further insights into the roles of Cdh11 in the development of the ear, we performed behavioral tests using Cdh11 knockout (KO) mice. KO mice showed reduced acoustic startle responses and increased thresholds for auditory brainstem responses, indicating moderate hearing loss.

Prolonged engraftment of transplanted hepatocytes in the liver by transient pro-survival factor supplementation using ex vivo mRNA transfection.

Cell transplantation therapy needs engraftment efficiency improvement of transplanted cells to the host tissues. Ex vivo transfection of a pro-survival gene to transplanted cells is a possible solution; however prolonged expression and/or genomic integration of the gene can be cancer promoting. To supply pro-survival protein only when it is needed, we used mRNA transfection, which exhibits transient protein expression profiles without the risk of genomic integration.