Bone marrow (BM) contains hematopoietic stem cells (HSC) which differentiate into all mature blood cells and marrow stromal cells that provide the microenvironment for hematopoietic stem/progenitor cells along with the capability to differentiate into mature cells of multiple mesenchymal tissues including fat, bone and cartilage. Recent studies indicate that adult BM also contains cells which can differentiate into nonhematopoietic cells of ectodermal, mesodermal and endodermal tissues other than hematopoietic tissues, including liver, pancreas, kidney, lung, skin, GI tract, heart, skeletal muscles and neural tissues. Studies describing this multipotentiality of BM cells have become a focus of interest because clinical applications in the treatment of damaged or degenerative diseases would be at hand using easily obtainable cells. However, presently, definitive evidence explaining the mechanism of this multipotentiality of bone marrow stem cells is lacking. In this review, we summarize recent progresses and controversies in the multipotentiality of adult bone marrow-derived stem cells to non-hematopoietic tissues.

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Treatment of defects of articullar cartilage remains a problem in orthopedic surgery because cartilage has little self-healing capability. Recently a new approach for repair of articular cartilage has appeared using tissue engineering to create cartilage-like tissues in a three-dimensional scaffolding with autologous chondrocytes. However, the number of autologous chondrocytes for autograft is limited. To solve this problem, mesenchymal stem cells (MSCs) sourced from bone marrow have been investigated as candidates for producing chondrocytes. One of the possible sources may be the placenta thrown away as a medical waste after the collection of cord blood. In this report, we determined the potential of chondrogenic differentiation of mesenchymal progenitor cells derived from chorionic villi of fetal human placenta (PDMSCs). Our results show that PDMSCs include cells which have chondrogenic differentiation potential and may serve as an alternative source of cells for repair of articular cartilage.

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We established a novel in vitro system to induce eye at high frequency using Xenopus early gastrulae. The eye formed in vitro is morphologically similar to the normal eye. Immunostaining showed that the eye induced in vitro had mature optic tissues. The cell lineage tracing revealed that eyes formed in vitro were derived from the animal cap cells. For functional analysis, we tried transplantation of eye induced in vitro. When eye induced in vitro was transplanted into stage 33 eyeless tadpole, the grafted eye rooted to the host tadpole and optic nerve was regenerated. Dil stanining of the optic nerve showed that regenerated optic nerve reached the tectum of the host brain. The grafted eye was retained after metamorphosis. The resultant juvenile frogs could perceive brightness using the grafted eye and control their skin color, suggesting that the eye formed in vitro could function normally.

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Neutrophils, a member of leukocytes, phagocytose and kill phathogenic organisms, thereby playing a crucial role in host defense. During phagocytosis, an enzyme called the phagocyte NADPH oxidase becomes activated to produce reactive oxygen species (ROS) that act as microbicidal agents. Activation of the oxidase must be strictly regulated, since ROS have a high reactivity and thus their overproduction causes inflammatory responses. The oxidase activation involves assembly of the cytosolic regulatory proteins p47^phox, p67^phox, p40^phox, and small GTPase Rac with the membrane-integrated cytochrome b₅₅₈, the catalytic core of the enzyme. Because the assembly requires a variety of protein-protein interactions mediated via modular domains, the knowledge of regulation of these interactions is important for our understanding of the molecular mechanism for the NADPH oxidase activation. On the basis of our current findings, here we discuss the activation mechanism with special attention to the induction and maintenance of the interactions between the oxidase factors.

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Ciliary neurotrophic factor (CNTF) has been known to inhibit the differentiation of presumptive rod photoreceptor cells; however, the underlying mechanisms have remained to be elucidated. We demonstrated that STAT3 activation, but not SHP2 activation, is responsible for the CNTF/gp130 signaling that inhibits expression of Rhodopsin and its upstream activator, crx, in the retinal explants derived from P0 mice (P0 retinal explants), utilizing STAT3-deficient retina and electroporation of dominant-negative form of STAT3 (STAT3F). We also demonstrated that STAT3 activation in presumptive rod photoreceptor cells at E18.5 is rapidly downregulated at P0, when Rhodopsin expression starts during retinal development. Persistent STAT3 activation in the P0 retinal explants prevented Rhodopsin expression and rapid upregulation of crx expression. STAT3-deficient retinas did not exhibit precocious Rhodopsin expression, although they exhibited precocious upregulation of crx mRNA. Thus, we conclude that downregulation of STAT3 activation is required, but insufficient, for rod photoreceptor cell differentiation in the postnatal retina.

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Disodium cromoglycate (DSCG) is a widely used anti-asthmatic drug with few side effects. One of the mechanisms by which DSCG suppresses asthma is prevention of anaphylactic release of chemical mediators from mast cells. However, it has also been reported that DSCG attenuates late asthmatic response and airway hyperresponsiveness, the induction mechanisms of which can not be explained simply by release of chemical mediators from mast cells. Mechanisms of anti-inflammatory effects of DSCG other than its mast-cell stabilising effect have been unclear. In this study, we evaluated effects of DSCG on early and late asthmatic response in guinea pig. Guinea pigs were alternately sensitized and challenged by exposure to mists of ovalbumin+Al(OH)₃ and ovalbumin, respectively. DSCG administered intratracheally before the fifth challenge dose-dependently inhibited late asthmatic response, but early asthmatic response was not affected. Interestingly, DSCG at 2 mg/kg potently suppressed increases in cysteinyl leukotrienes and thromboxane A₂ in the lung during late asthmatic response. Eosinophilia was slightly reduced by DSCG. The inhibitory effect of DSCG on late asthmatic response is apparently due to inhibition of release of arachidonic acid metabolites.

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It is reported that chalcone derivatives have various biological activities such as anti-inflammatory, anti-tumor and anti-oxidant activity. We examined effects of 2'-hydroxychalcone derivatives on the production of prostaglandin (PG) E₂, nitric oxide (NO) and tumor necrosis factor (TNF)-α. Among fourteen 2'-hydroxychalcone derivatives, 2',4-dihydroxy-4'-methoxychalcone (compound 3), 2',4-dihydroxy-6'-methoxychalcone (compound 8) and 2'-hydroxy-4'-methoxychalcone (compound 9) showed potent inhibitory activity forward the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced PGE₂ production in rat peritoneal macrophages through the suppression of the induction of cyclooxygenase (COX)-2. Moreover, these three compounds inhibited both NO and TNF-α production through the inhibition of the expression of iNOS and TNF-α mRNA in the murine macrophage cell line RAW 264.7. These three compounds also suppressed the LPS-induced activation of NF-κB and AP-1 in RAW 264.7 cells, indicating that the inhibition of the production of PGE₂, NO and TNF-α is due to the inhibition of NF-κB and AP-1 activation. Our findings suggested that the anti-inflammatory activity of the 2'-hydroxychalcone derivatives is induced by the inhibition of the production of pro-inflammatory mediators such as PGE₂, NO and TNF-α. It was also suggest that the chalcone derivatives might be lead compounds for anti-inflammatory drugs.

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