Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers.

Liver progenitor cells have the potential to repair and regenerate a diseased liver. The success of any translational efforts, however, hinges on thorough understanding of the fate of these cells after transplant, especially in terms of long-term safety and efficacy. Here, we report transplantation of a liver progenitor population isolated from human fetal livers into immune-permissive mice with follow-up up to 36 weeks after transplant. We found that human progenitor cells engraft and differentiate into functional human hepatocytes in the mouse, producing albumin, alpha-1-antitrypsin, and glycogen. They create tight junctions with mouse hepatocytes, with no evidence of cell fusion. Interestingly, they also differentiate into functional endothelial cell and bile duct cells. Transplantation of progenitor cells abrogated carbon tetrachloride-induced fibrosis in recipient mice, with downregulation of procollagen and anti-smooth muscle actin. Paradoxically, the degree of engraftment of human hepatocytes correlated negatively with the anti-fibrotic effect. Progenitor cell expansion was most prominent in cirrhotic animals, and correlated with transcript levels of pro-fibrotic genes. Animals that had resolution of fibrosis had quiescent native progenitor cells in their livers. No evidence of neoplasia was observed, even up to 9 months after transplantation. Human fetal liver progenitor cells successfully attenuate liver fibrosis in mice. They are activated in the setting of liver injury, but become quiescent when injury resolves, mimicking the behavior of de novo progenitor cells. Our data suggest that liver progenitor cells transplanted into injured livers maintain a functional role in the repair and regeneration of the liver. Stem Cells 2018;36:103-113.

A complication of double lumen hemocatheter guide wire entrapment in a hemodialysis patient.

Double lumen hemocatheter is commonly used for temporary hemodialysis patient and various complications have been documented but few reports of guide wire-related complications. We report a complication of double lumen hemocatheter guide wire entrapment in a 43-year-old female of type 1 diabetes mellitus and hemodialysis patient. She was admitted for left arteriovenous shunt dysfunction and right internal jugular vein hemocatheter chamber clotting was found while on hemodialysis, so a new hemocatheter was changed over guide wire. Guide wire was introduced without any resistance and the clotting hemocatheter was removed. During the procedure, the J-tipped guide wire could not be withdrawn and portable chest radiography revealed the J-tip of the guide wire was in the right ventricle near the region of tricuspid valve. Fluoroscopy was arranged and it also confirmed the J-tip was lying in the ventricle near the tricuspid valve where it was stuck. Snare catheter kit was inserted through the 10 Fr sheath and the cardiologist untied the knot by endovascular snare and removed the guide wire smoothly. This report emphasizes the importance of awareness on guide wire entrapment while inserting double lumen hemocatheter. When a guide wire became hard to withdraw, extracting an entrapped guide wire with fluoroscopy guide and snare catheter is a preferable and minimal invasive approach.

Low-fat, low-glycemic load diet and gene expression in human prostate epithelium: a feasibility study of using cDNA microarrays to assess the response to dietary intervention in target tissues.

PURPOSE: We examined the feasibility of using gene expression changes in human prostate epithelium as a measure of response to a dietary intervention. MATERIALS AND METHODS: Eight men with newly diagnosed prostate cancer were randomized to a low-fat/low-glycemic load intervention arm (<20% energy from fat and total daily glycemic load <100) or a "standard American" control arm (approximately 35% energy from fat and total daily glycemic load >200). Prostate tissue was collected before randomization and approximately 6 weeks later, at the time of radical prostatectomy. Epithelium was acquired by laser capture microdissection, and transcript abundance levels were measured by cDNA microarray hybridization and confirmed by quantitative reverse transcription-PCR. RESULTS: Men in the intervention arm consumed 39% less total energy (P = 0.004) and the difference in weight change between intervention and control arms was -6.1 kg (P = 0.02). In the intervention arm, 23 (0.46%) of 5,711 cDNAs with measurable expression were significantly altered (P < 0.05; false discovery rate,

Influence of surgical manipulation on prostate gene expression: implications for molecular correlates of treatment effects and disease prognosis.

PURPOSE: Measurements of tissue gene expression are increasingly used for disease stratification, clinical trial eligibility, and assessment of neoadjuvant therapy response. However, the method of tissue acquisition alone could significantly influence the expression of specific transcripts or proteins. This study examines whether there are transcript alterations associated with surgical resection of the prostate gland by radical retropubic prostatectomy. MATERIALS AND METHODS: Twelve patients with clinically localized prostate cancer underwent immediate in situ prostate biopsy after induction of anesthesia for radical prostatectomy. Ex vivo prostate biopsies were performed immediately after surgical removal. Prostate epithelium was acquired by laser-capture microdissection, and transcript abundance levels were quantitated by cDNA microarray hybridization and confirmed by quantitative polymerase chain reaction. Data were analyzed by paired, two-sample t test using Statistical Analysis of Microarray algorithms, and linear models were fit as a function of clinical characteristics. RESULTS: Of 5,753 cDNAs with measurable expression in prostate epithelium, 88 (1.5%) were altered as a result of surgery (false-discovery rate < or = 10%), representing 62 unique genes. These included transcripts encoding acute phase response proteins, IER2 and JUNB, and regulators of cell proliferation, p21Cip1 and KLF6. Of the clinical characteristics examined, including patient age, prostate volume, serum prostate-specific antigen, blood loss, and operative time, only gland volume was significantly and negatively associated with the magnitude of gene expression difference between pre- and postsurgical specimens. CONCLUSION: Surgical manipulation results in significant gene expression changes. Molecular analyses of surgical samples should recognize that transcript alterations occur rapidly, and these results are important when designing and analyzing molecular correlates of clinical studies.