In Vivo Stem Cell Imaging Principles and Applications

Stem cells are the foundational cells for every organ and tissue in our body. Cell-based therapeutics using stem cells in regenerative medicine have received attracting attention as a possible treatment for various diseases caused by congenital defects. Stem cells such as induced pluripotent stem cells (iPSCs) as well as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), and neuroprogenitors stem cells (NSCs) have recently been studied in various ways as a cell-based therapeutic agent. When various stem cells are transplanted into a living body, they can differentiate and perform complex functions. For stem cell transplantation, it is essential to determine the suitability of the stem cell-based treatment by evaluating the origin of stem, the route of administration, In vivo bio-distribution, transplanted cell survival, function, and mobility. Currently, these various stem cells are being imaged In vivo through various molecular imaging methods. Various imaging modalities such as optical imaging, magnetic resonance imaging (MRI), ultrasound (US), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) have been introduced for the application of various stem cell imaging. In this review, we discuss the principles and recent advances of In vivo molecular imaging for application of stem cell research.

Phytochemical Constituents of the Root Bark from Morus alba and Their Il-6 Inhibitory Activity

Morus alba L., known as white mulberry, is a medicinal plant belongs to family Moraceae. It has long been used commonly in Ayurvedic for the treatment of lung-heat, cough, asthma, hematemesis, dropsy and hypertension. In the present study, seven prenylated flavonoids, along with four benzofuran compounds were isolated by means of repeated column chromatography. The structures of the known compounds were identified as kuwanon G (1), kuwanon E (2), kuwanon T (3), morusin (4), sanggenon A (5), sanggenon M (6), sanggenol A (7), moracin R (8), mulberofuran G (9), mulberofuran A (10) and mulberofuran B (11), by comparing their spectroscopic data with those reported in the literature. For these isolates, containing trace compounds, the inhibitory activity against IL-6 production in TNF-α stimulated MG-63 cells was examined. All isolated compounds (1

Sodium butyrate has context-dependent actions on dipeptidyl peptidase-4 and other metabolic parameters

Sodium butyrate (SB) has various metabolic actions. However, its effect on dipeptidyl peptidase 4 (DPP-4) needs to be studied further. We aimed to evaluate the metabolic actions of SB, considering its physiologically relevant concentration. We evaluated the effect of SB on regulation of DPP-4 and its other metabolic actions, both in vitro (HepG2 cells and mouse mesangial cells) and in vivo (high fat diet [HFD]-induced obese mice). Ten-week HFD-induced obese C57BL/6J mice were subjected to SB treatment by adding SB to HFD which was maintained for an additional 16 weeks. In HepG2 cells, SB suppressed DPP-4 activity and expression at sub-molar concentrations, whereas it increased DPP-4 activity at a concentration of 1,000 µM. In HFD-induced obese mice, SB decreased blood glucose, serum levels of insulin and IL-1β, and DPP-4 activity, and suppressed the increase in body weight. On the contrary, various tissues including liver, kidney, and peripheral blood cells showed variable responses of DPP-4 to SB. Especially in the kidney, although DPP-4 activity was decreased by SB in HFD-induced obese mice, it caused an increase in mRNA expression of TNF-α, IL-6, and IL-1β. The pro-inflammatory actions of SB in the kidney of HFD-induced obese mice were recapitulated by cultured mesangial cell experiments, in which SB stimulated the secretion of several cytokines from cells. Our results showed that SB has differential actions according to its treatment dose and the type of cells and tissues. Thus, further studies are required to evaluate its therapeutic relevance in metabolic diseases including diabetes and obesity.

Anti-inflammatory Effect of Dactyloquinone B and Cyclospongiaquinone-1 Mixture in RAW264.7 Macrophage and ICR Mice

Sesquiterpene-quinone is a class of secondary metabolites frequently encountered from marine sponge. The present study was designed to examine the anti-inflammatory action of sponge-derived dactyloquinone B (DQB) and cyclospongiaquinone-1 (CSQ1) mixture using lipopolysaccharide (LPS)-induced inflammatory responses. We measured the production of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) and expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. TNF-alpha, IL-1beta, and IL-6 production, which increased by treatment with LPS, were significantly inhibited by DQB and CSQ1 mixture. It also decreased the production of NO production, and iNOS and COX-2 expression. Furthermore, it reduced 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema of ICR mice. These results demonstrate that sesquiterpene-quinone, DQB and CSQ1 mixture, might serve as a chemical pipeline for the development of anti-inflammatory agent.

Hutchinson-Gilford Progeria Syndrome with G608G LMNA Mutation

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition originally described by Hutchinson in 1886. Death result from cardiac complications in the majority of cases and usually occurs at average age of thirteen years. A 4-yr old boy had typical clinical findings such as short stature, craniofacial disproportion, alopecia, prominent scalp veins and sclerodermatous skin. This abnormal appearance began at age of 1 yr. On serological and hormonal evaluation, all values are within normal range. He was neurologically intact with motor and mental development. An echocardiogram showed calcification of aortic and mitral valves. Hypertrophy of internal layer at internal carotid artery suggesting atherosclerosis was found by carotid doppler sonography. He is on low dose aspirin to prevent thromboembolic episodes and on regular follow up. Gene study showed typical G608G (GGC- > GGT) point mutation at exon 11 in LMNA gene. This is a rare case of Hutchinson-Gilford progeria syndrome confirmed by genetic analysis in Korea.

Azasugar Nucleotide-containing Phosphorothioate Oligonucleotides as an AIDS Therapeutic Drug

A series of modified oligonucleotides containing P=S backbone and a six-membered azasugar (6-AZS) were synthesized and tested for their ability to inhibit human immunodeficiency virus (HIV) in vitro without the aid of any transfecting agents. While P=S oligonucleotides with natural nucleotides had little anti-HIV-1 activity, six-membered azasugar nucleotide (6-AZN)-containing P=S oligonucleotides (AZPSON) potently inhibited the HIV-1/SHIV production and syncytium formation in vitro (EC50 = 0.02~0.2 micro M) without cytotoxicity up to 100 micro M. AZPSONs are enzymatically stable over 6 days in culture supernatant. Phosphodiester (P=O) backbone only or mixed backbone (P=O and P=S) oligonucleotides that contain 6-AZN did not exhibit anti-HIV-1 activity. The anti-HIV-1 capacity of AZPSON seems to depend on the number and/or distribution patterns of 6-AZN in the oligonucleotides. The oligomer 2198, most effective for anti-HIV-1 activity among the AZPSONs, was much more effective than ddI or ddC in anti-HIV activity. Particularly noteworthy is that the anti-HIV-1 activity of AZPSON-2198 was better than AZT in the long-lasting efficacy after a single treatment.

Construction and Immuno - biochemical Studies of Chimeric Polioviruses Expressing Multivalent V3 / PND - concatamers of Human Immunodeficiency Virus Type 1

Poliovirus Sabin 1 strain has its own special features that make it a particularly attractive live recombinant mucosal vaccine vehicle. Sabin 1 cDNA was manipulated to have multiple cloning site and viral specific 3C-protease cutting site at the N-terminal end of the polyprotein, named RPS-vax system HIV-1 V3- and principal neutralizing domain (PND)-concatamers were successfully cloned into the multiple cloning site of the vector system and produced expected chimeric viruses by transfection of their RNA transcripts into HeLa cells. These chimeric viruses have shown to express introduced HIV-1 subgenome concatamers efficiently during their replication in the infected HeLa cells. Expressed proteins were confirmed to retain the wild type structures at least in parts. Replication capacity of the chimeric viruses was slightly lower than that of wild type Sabin 1 likely to be due to delay in processing steps during their replication. Differing from the virulent Mahoney vectors, the rec-Sabin 1 chimeric viruses maintained the foreign gene stably during the serial passages. These chimeric viruses have also shown to be able to induce specific humoral immunity to the introduced vaccine proteins when inoculated into the poliovirus receptor-expressing transgenic (Tg-PVR) mice. Antiserum obtained from the immunized transgenic mice showed to have neutralizing capacity to HIV-1 in vitro. These results strongly suggest that the chimeric viruses expressing HIV-1 vaccine epitopes can be used as a good live mucosal vaccine candidate against AIDS.