Scintigraphic tracking of mesenchymal stem cells after intravenous regional limb perfusion and subcutaneous administration in the standing horse.

OBJECTIVE: To assess distribution, uptake, and persistence of radiolabeled mesenchymal stem cells (MSC) using scintigraphy after intravenous regional limb perfusion (RLP) and subcutaneous injections in standing, sedated horses. STUDY DESIGN: Experimental study. ANIMALS: Horses (n = 12). METHODS: Six horses had RLP performed through the cephalic vein on 1 limb and subcutaneous injection in the metacarpal area in the opposite limb. The other 6 horses had RLP performed through the lateral palmar digital vein and subcutaneous injection in the coronary band. A pneumatic tourniquet was used for the RLP. MSC were labeled with technetium-HMPAO. Scintigraphic images were obtained at the time of injection, 1, 6, and 24 hours later. Results of RLP were compared with results from previous studies where similar injections were performed in anesthetized horses. RESULTS: Both RLP techniques led to greater variability, lower uptake, lower persistence, and poorer distribution when compared to results previously reported for horses under general anesthesia. The subcutaneous injections in the metacarpal area and coronary band resulted in MSC loss to the general circulation but no evidence of local migration. CONCLUSION: Due to partial or complete failure of the tourniquet, RLP performed in the standing horse as described is less efficient than performed under general anesthesia. Further work is needed to optimize the use of tourniquets to perform RLP for MSC administration in standing patients. The subcutaneous injections did not result in local migration in these normal horses.

Primary biliary cirrhosis is associated with altered hepatic microRNA expression.

MicroRNAs (miRNAs) are small RNA molecules that negatively regulate protein coding gene expression and are thought to play a critical role in many biological processes. Aberrant levels of miRNAs have been associated with numerous diseases and cancers, and as such, miRNAs have gain much interests as diagnostic biomarkers, and as therapeutic targets. However, their role in autoimmunity is largely unknown. The aims of this study are to: (1) identify differentially expressed miRNAs in human primary biliary cirrhosis (PBC); (2) validate these independently; and (3) identify potential targets of differentially expressed miRNAs. We compared the expression of 377 miRNAs in explanted livers form subjects with PBC versus controls with normal liver histology. A total of 35 independent miRNAs were found to be differentially expressed in PBC (p < 0.001). Quantitative PCR was employed to validate down-regulation of microRNA-122a (miR-122a) and miR-26a and the increased expression of miR-328 and miR-299-5p. The predicted targets of these miRNAs are known to affect cell proliferation, apoptosis, inflammation, oxidative stress, and metabolism. Our data are the first to demonstrate that PBC is characterized by altered expression of hepatic miRNA; however additional studies are required to demonstrate a causal link between those miRNA and the development of PBC.