Regeneration of Soft Tissues Is Promoted by MMP1 Treatment after Digit Amputation in Mice

The ratio of matrix metalloproteinases (MMPs) to the tissue inhibitors of metalloproteinases (TIMPs) in wounded tissues strictly control the protease activity of MMPs, and therefore regulate the progress of wound closure, tissue regeneration and scar formation. Some amphibians (i.e. axolotl/newt) demonstrate complete regeneration of missing or wounded digits and even limbs; MMPs play a critical role during amphibian regeneration. Conversely, mammalian wound healing re-establishes tissue integrity, but at the expense of scar tissue formation. The differences between amphibian regeneration and mammalian wound healing can be attributed to the greater ratio of MMPs to TIMPs in amphibian tissue. Previous studies have demonstrated the ability of MMP1 to effectively promote skeletal muscle regeneration by favoring extracellular matrix (ECM) remodeling to enhance cell proliferation and migration. In this study, MMP1 was administered to the digits amputated at the mid-second phalanx of adult mice to observe its effect on digit regeneration. Results indicated that the regeneration of soft tissue and the rate of wound closure were significantly improved by MMP1 administration, but the elongation of the skeletal tissue was insignificantly affected. During digit regeneration, more mutipotent progenitor cells, capillary vasculature and neuromuscular-related tissues were observed in MMP1 treated tissues; moreover, there was less fibrotic tissue formed in treated digits. In summary, MMP1 was found to be effective in promoting wound healing in amputated digits of adult mice. © 2013 Mu et al

MicroRNA expression in bone marrow-derived human multipotent Stromal cells

Abstract Background Multipotent stromal cells (MSCs) are being studied in the field of regenerative medicine for their multi-lineage differentiation and immunoregulatory capacity. MicroRNAs (miRNAs) are short non-coding RNAs that are responsible for regulating gene expression by targeting transcripts, which can impact MSC functions such as cellular proliferation, differentiation, migration and cell death. miRNAs are expressed in MSCs; however, the impact of miRNAs on cellular functions and donor variability is not well understood. Eight MSC lines were expanded to passages 3, 5 and 7, and their miRNA expression was evaluated using microarray technology. Results Statistical analyses of our data revealed that 71 miRNAs out of 939 examined were expressed by this set of MSC lines at all passages and the expression of 11 miRNAs were significantly different between passages 3 and 7, while the expression of 7 miRNAs was significantly different between passages 3 and 5. The expression of these identified miRNAs was evaluated using RT-qPCR for both the first set of MSC lines (n = 6) and a second set of MSC lines (n = 7) expanded from passages 4 to 8. By RT-qPCR only 2 miRNAs, miR-638 and miR-572 were upregulated at passage 7 compared to passage 3 in the first set of MSC lines by 1.71 and 1.54 fold, respectively; and upregulated at passage 8 compared to passage 4 in the second set of MSC lines, 1.35 and 1.59 fold, respectively. Conclusions The expression of miR-638 and miR-572 can distinguish MSCs from two different passages of cell culture. These results may be useful in establishing critical quality attributes of MSCs and determining whether changes in these two miRNAs impact cellular functions

Skeletal muscle-derived stem cells differentiate into hepatocyte-like cells and aid in liver regeneration

The liver is unique for its ability to regenerate after injury, however, critical injuries or disease cause it to lose this quality. Stem cells have been explored as a possibility to restore the function of seriously damaged livers, based on their self-renewability and multiple differentiation capacity. These experiments examine the ability of muscle derived stem cells (MDSCs) to differentiate into hepatocyte-like cells in vitro and acquire functional liver attributes for repairing damaged livers. In vitro experiments were performed using MDSCs from postnatal mice and mouse hepatocyte cell lines. Our data revealed that MDSCs differentiated into hepatocyte-like cells and expressed liver cell markers, albumin, hepatocyte nuclear factor 4α, and alpha feto-protein, both at the RNA and protein level. Additionally, in vivo studies showed successful engraftment of MDSCs into hepatectomized mouse livers of mice. These results provide evidence suggesting that MDSCs have the capacity to differentiate into liver cell-like cells and may serve as potential candidates to aid in liver regeneration

IL-13Rα2 gene expression is a biomarker of adverse outcome in patients with adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC