EDITOR'S PICK: How to grow muscle cells in a dish
Smooth muscle cells (SMCs) are a crucial cellular component of many parts of the body, including blood vessels, the intestines, and the lungs. SMCs in the blood vessels are involved in several causes of heart disease and understanding how SMCs are generated is important for designing therapies for such diseases. It is also knowledge that could be used to engineer tissues in the laboratory, for example new blood vessels for use in bypass surgery.
In a study that appears online on November 9, in advance of publication in the December print issue of the Journal of Clinical Investigation, Catherine Verfaille and colleagues at the University of Minnesota Medical School, Minneapolis, show that SMCs can be generated from multipotent adult progenitor cells (MAPCs) isolated from the bone marrow of rats, mice, pigs, and humans. These cells only generated SMCs if exposed to the soluble factor TGF-beta or TGF-beta and another soluble factor PDGFB. SMC development from MAPCs occurred along the normal pathway of SMC development and the cells that were generated had all the functions of normal SMCs. This study therefore identifies a model system for studying the effects of potential therapeutics on SMC development and SMCs. It also describes a potential source of SMCs for engineering tissues.
TITLE: Cytokine-induced differentiation of multipotent adult progenitor cells into functional smooth muscle cells
AUTHOR CONTACT:
Catherine M. Verfaillie
Katholieke Universiteit Leuven, Leuven, Belgium.
Phone: +32-16-33-02-95; Fax: +32-16-33-02-94; E-mail: catherine.verfaillie@med.kuleuven.be.
View the PDF of this article at: https://www.the-jci.org/article.php?id=28184
AUTOIMMUNITY: Multiple regulatory cell types can't keep self-destructive immune cells under control
Multiple sclerosis (MS) is an autoimmune disease that occurs when cells of the immune system attack nerves in the brain. Although it is not clear exactly why this self destruction is able to occur, it has been shown that other immune cells that normally keep the destructive ones in check (known as regulatory T cells) are impaired in individuals with MS. Previous studies have focused on a regulatory T cell subset known as the CD4+CD25high regulatory T cell subset, but in a study appearing online on November 9, in advance of publication in the December print issue of the Journal of Clinical Investigation, researchers from Harvard University, now show that IL-10 producing regulatory T cells (Tr1 cells) are also impaired in individuals with MS.
David Hafler and colleagues showed that T cells from patients with MS produced substantially less IL-10 when stimulated ex vivo with antibodies specific for CD3 and CD46 than T cells from healthy individuals. This inability to induce a Tr1 cell phenotype was associated with altered expression of CD46 cytoplasmic isoforms upon activation. This study shows that a second regulatory T cell population (the Tr1 cells) is impaired in individuals with MS and the authors speculate that, as for the CD4+CD25high regulatory T cell subset, this defect is likely to be observed in patients with other autoimmune diseases, such as rheumatoid arthritis.
TITLE: Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis
AUTHOR CONTACT:
David A. Hafler
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617)-525-5330; Fax: (617)-525-5333; E-mail: dhafler@rics.bwh.harvard.edu.
Anne L. Astier
Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Phone: (617)-525-5330; Fax: (617)-525-5333; E-mail: aastier@rics.bwh.hgarvard.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=29251
CARDIOLOGY: TRPC6 is big hearted
The causes of heart failure are extremely diverse and include high blood pressure, a heart attack, and inherited genetic abnormalities. Two of the reasons these events all trigger heart failure is that they result in the muscle cells of the heart getting bigger (a process known as cardiac hypertrophy) and they cause the muscle cells to change the types of protein they express (and so change their functions). Understanding the molecular mechanisms behind these changes is therefore of interest for developing new therapeutics for the treatment of individuals with heart disease.
Now, in a study appearing online on November 9, in advance of publication in the December print issue of the Journal of Clinical Investigation, Eric Olsen and colleagues from the University of Texas Southwestern Medical Center have shown that in mice, increased expression of a protein known as TRPC6 is important for the muscle cells of the heart to grow and change their function under conditions that trigger heart failure. Upregulation of TRPC6 was mediated by a calcium responsive signaling molecule (calcineurin) and overexpression of TRPC6 in the heart caused mice to be more susceptible to lethal heart failure. As TRPC6 was also shown to be expressed at high levels in failing human hearts, the authors suggest that TRPC6 might be a viable therapeutic target for the treatment of heart failure.
TITLE: TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling
AUTHOR CONTACT:
Eric N. Olsen
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Phone: (214) 648-1187; Fax: (214) 648-1196; E-mail: Eric.Olson@utsouthwestern.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=27702
BONE BIOLOGY: Chondrocytes: new contractors to help vitamin D build bones
A lack of vitamin D in the diet causes several bone diseases, including rickets and osteoporosis. This is because, through binding the vitamin D receptor (VDR), vitamin D controls the amount of calcium and phosphates (which are both essential for maintaining healthy bones) in our bodies. It is thought that these effects of vitamin D are mediated by the VDR in the intestines and kidney. However, the VDR is also expressed by cells in the bone known as chondrocytes, but its effects on this cell type have not previously been described.
Now, in a study appearing online on November 9 in advance of publication in the December print issue of the Journal of Clinical Investigation, Geert Carmeliet and colleagues from Katholieke Universiteit Leuven, Belgium, have shown that VDR expression by chondrocytes is required for normal bone development in young mice. Further analysis showed that in the absence of VDR in chondrocytes, one of the cells required for normal bone development (osteoclasts) was not present in sufficient numbers. In addition, phosphate levels in the blood were abnormally high. This study, therefore defines a role for chondrocytes in bone development.
TITLE: Vitamin D receptor in chondrocytes promotes osteoclastogenesis and regulates FGF23 production in osteoblasts
AUTHOR CONTACT:
Geert Cameliet
Katholieke Universiteit Leuven, Leuven, Belgium.
Phone: +32-16-34-5974; Fax: +32-16-34-5934; E-mail: geert.carmeliet@med.kuleuven.be.
View the PDF of this article at: https://www.the-jci.org/article.php?id=29463
Journal
Journal of Clinical Investigation