Mesenchymal Stem Cells

A pretty “sweet” Stem Cells article has been hitting the news this week.

Mesenchymal stem cells found to be effective in treating models of atherosclerosis in vitro and in vivo

Researchers find that a small fraction of perivascular mesenchymal-like stem cells contribute to fibrosis in organs after injury, and that ablation of these cells can improve organ function

Exciting magnetic nanoparticle technology improves mesenchymal stem cell mediated bone repair

Researchers further our understanding of the indirect means by which the nervous system can modulate stem cell systems, underlining a role for dopamine in the mobilization of mesenchymal progenitor cells

Researchers discover that delayed hypoxia treatment can enhance bone healing in a mouse model

The generation of an miRNA-mRNA interaction map in cells that make up the bone marrow niche allows regulatory pathways for signalling factors to be understood.

Alterations in the Cellular Immune Compartment of Patients Treated with Third-Party Mesenchymal Stromal Cells Following Allogeneic Hematopoietic Stem Cell Transplantation

From Stem Cells

Allogeneic hematopoietic stem cell transplantation is often complicated by graft-versus-host disease (GVHD) mediated by the donors immune cells (Ferrara et al) and novel intervention strategies are highly sought after.   Mesenchymal stem cells (MSCs) are known to have immunoregulatory properties and have been applied in clinical trials (Le Blanc et al), although few reports have shed light on the effects of MSCs on the patient's immune system (Dander et al).   Now, in a study published in Stem Cells, researchers from the laboratory of Katarina Le Blanc at the Karolinska University Hospital, Stockholm, Sweden have investigated the alterations in the immune system caused by third-party (i.e. from an unrelated source) MSC treatment to aid in the design of future clinical studies and to establish novel monitoring procedures (Jitschin and Mougiakakos et al).

“Natriuretic Peptide Receptor A Signaling Regulates Stem Cell Recruitment and Angiogenesis: A Model to Study Linkage Between Inflammation and Tumorigenesis”

Natriuretic peptide receptor A (NPRA) is expressed on cells in inflamed or injured tissues and in tumours (Kong et al and Wang et al) and through cGMP-dependent protein kinase (PKG) signalling (Airhart et al and Chen et al), it upregulates genes affecting cell proliferation and inflammation, although a greater level of detail remains to be uncovered. Researchers from the group of Subhra Mohapatra at the University of South Florida, Tampa, Florida, USA have previously shown that NPRA is an early biomarker for human prostate cancer (Wang et al) as well as recently establishing NPRA as a biomarker for melanoma, colon, and pancreatic cancer, and have reasoned that NPRA signaling may promote tumourigenesis by influencing recruitment of immune and progenitor cells, thereby fostering angiogenesis. In their newest study, published in Stem Cells, the group use NPRA-knock out (NPRA-KO) mice as a model and find that that NPRA signaling is indeed linked to angiogenesis partially through progenitor cell recruitment (Mallela et al).

"Comparison of Drug and Cell-Based Delivery: Engineered Adult Mesenchymal Stem Cells Expressing Soluble Tumor Necrosis Factor Receptor II Prevent Arthritis in Mouse and Rat Animal Models"

Tumor necrosis factor-α (TNFα) is a cytokine that mediates normal homeostatic mammalian processes (Schaible et al and Wajant et al) but has been linked to the systemic autoimmune disease Rheumatoid Arthritis (RA), where a TNFα induced cytokine cascade causes inflammation and joint destruction. Blocking TNFα function would therefore seem a viable means to treat RA. Etanercept, a TNF receptor (TNFR) linked to the immunoglobin Fc fragment and two monoclonal antibodies, infliximab and adalimumab are three TNFα inhibitors approved in the United States (Mazza et al), while TNFα blockers certolizumab pegol and golimumab are also utilised (Wallis and Scallon et al). However, the necessity for systemic delivery leads to certain unwanted side-effects, and so site-specific drug action is being sought after. To this end, in a report in Stem Cells Translational Medicine, researchers led by Joseph D. Mosca at Osiris Therapeutics, Inc., Baltimore, Maryland, USA have published the results of their studies on the potential use of mesenchymal stem cell (MSC)-based TNFR delivery and the efficacy of this treatment compared to the use of etanercept (Liu et al).