Articles in 2010

Mesenchymal stem cells (MSCs) can form different cell types in culture, but their potential to build new tissue in various disorders where tissue is damaged has not been realized. A study now shows how mature cells from blood vessels are a new source of MSCs that may be used to regenerate cartilage and bone (pages 1400–1406).

To truly know whether a stem cell has the developmental flexibility to give rise to new, therapeutic tissue types, the cells must undergo a definitive test in which they are injected into mice and observed. Yet many say this measure is too slow, too expensive and too unreliable. Elie Dolgin goes in search of a replacement.

Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. A serum antibody preexisting in middle-aged adults cross-reacts with, but does not protect against, 2009 H1N1 influenza virus. The existence of this antibody may account for the unusual age distribution of severe flu cases during pandemics.

Expression of miR-124, a microglial microRNA, reduces disease in a mouse model of multiple sclerosis by inhibiting the transcription factor C/EBP-α and its downstream target PU.1.

Dysfunction of the dopamine neurotransmitter system has long been implicated in depression. Now, Fang Liu and colleagues show that the interaction between two dopamine receptor subtypes is increased in the brain of subjects with major depression. Blocking this interaction in rodent models of depression can result in antidepressant-like effects.

One complication arising from gastrointestinal surgery is ileus, in which local manipulation of the intestine leads to dysmotility and paralysis of the entire intestine. Christian Kurts and his colleagues find that after surgery T helper type 1 memory cells are activated by intestinal dendritic cells via interleukin-12, and migration of memory T cells through the portal vein induces paralysis of unmanipulated sites. Inhibition of interleukin-12 or prevention of lymphocyte egress with FTY720 prevents ileus and suggests new targets for therapeutic intervention.

Brain injury after stroke requires glutamate receptor activation of neuronal nitric oxide synthase (nNOS), but inhibiting either of these proteins can cause side effects. Now, Dong-Ya Zhu and colleagues show that a drug that blocks the interaction between nNOS and a glutamate receptor docking protein can reduce stroke damage in vivo, with no observed side effects.

Deficiencies with current in vitro methods to assess cancer invasion prompted Todd Ridky and his colleagues to design a three-dimensional human organotypic epithelial cancer model using primary epithelial cells from multiple stratified epithelial tissues. The model recapitulates many of the features of tumor progression, including epithelial invasion through the intact basement membrane and supporting stroma. Studying epithelial tumor cell invasion in a more physiologic manner may help identify potential therapeutic targets for a range of epithelial tumors.

By acting on the P2X₇ receptor, ATP released upon cell damage functions as a danger signal to promote acute graft-versus-host disease after bone marrow transplantation in mice.

Physiological Stat3 signaling is temporally restricted. In cancer, Stat3 activity is often persistently elevated and fosters progression through its effects on tumor cells and their microenvironment. This report identifies the reciprocal positive regulation of S1PR1 and Stat3 in tumors as a mechanism by which tumor cells and their environment crosstalk to maintain Stat3 activity. This persistent loop is required for tumor progression and metastasis and could be a potential therapeutic target to block oncogenic Stat3 signaling.

Under certain conditions, endothelial cells can transform into mesenchymal cell types, a process known as endothelial-to-mesenchymal transition. Damian Medici et al. now provide evidence that this type of transition contributes to the generation of the ossified lesions of individuals with fibrodysplasia ossificans progressiva. Experiments in mice and in cultured endothelial cells indicate that activation of the ALK2 receptor in endothelial cells endows them with the ability to differentiate into a number of cell types.

The authors characterize a previously undescribed function of Snf5 that involves interaction with the transcription factor Gli1 and downregulation of its activity via chromatin remodeling. Snf5 is shown to restrict Hedgehog (Hh) signaling in normal development and cancer. Hh inhibition emerges as a potential therapeutic strategy for malignant rhabdoid tumors in which Snf5 is commonly lost.

Dry mucosal surfaces, such as the eyes and mouth, are a major clinical problem, particularly in the elderly or in individuals taking certain medications. Now, Carlos Belmonte and his colleagues show that cooling of the eye, caused by surface evaporation during eye opening, can induce tearing by stimulating TRPM8-expressing cold-sensing nerve endings.

Grazyna Palczewska and her colleagues use the noninvasive imaging modality of two-photon microscropy to study the retinoid cycle in the mammalian eye at the subcellular level. They perform spectral analyses of endogenous fluorophores, including fluorescent retinyl esters in subcellular structures called retinosomes, as well as their potentially harmful condensation products. This may prove useful in assessing retinal changes in the human eye at the earliest stage and long before retinal diseases become apparent and result in loss of vision.

The transition from androgen-dependent to castration-resistant prostate cancer is a lethal event. N-cadherin seems to be a major cause underlying this transition, and targeting this adhesion molecule may have positive clinical benefit.