Endothelial Progenitor Cells (EPCs) as Gene Carrier System for Rat Model of Human Glioma

Due to their unique property to migrate to pathological lesions, stem cells are used as a delivery vehicle for therapeutic genes to tumors, especially for glioma. It is critically important to track the movement, localization, engraftment efficiency and functional capability or expression of transgenes of selected cell populations following transplantation. The purposes of this study were to investigate whether 1) intravenously administered, genetically transformed cord blood derived EPCs can carry human sodium iodide symporter (hNIS) to the sites of tumors in rat orthotopic model of human glioma and express transgene products, and 2) whether accumulation of these administered EPCs can be tracked by different in vivo imaging modalities.Collected EPCs were cultured and transduced to carry hNIS. Cellular viability, differential capacity and Tc-99m uptake were determined. Five to ten million EPCs were intravenously administered and Tc-99-SPECT images were acquired on day 8, to determine the accumulation of EPCs and expression of transgenes (increase activity of Tc-99m) in the tumors. Immunohistochemistry was performed to determine endothelial cell markers and hNIS positive cells in the tumors. Transduced EPCs were also magnetically labeled and accumulation of cells was confirmed by MRI and histochemistry. SPECT analysis showed increased activity of Tc-99m in the tumors that received transduced EPCs, indicative of the expression of transgene (hNIS). Activity of Tc-99m in the tumors was also dependent on the number of administered transduced EPCs. MRI showed the accumulation of magnetically labeled EPCs. Immunohistochemical analysis showed iron and hNIS positive and, human CD31 and vWF positive cells in the tumors.EPC was able to carry and express hNIS in glioma following IV administration. SPECT detected migration of EPCs and expression of the hNIS gene. EPCs can be used as gene carrier/delivery system for glioma therapy as well as imaging probes

A 5-year course of predominantly obsessive vs. mixed subtypes of obsessive-compulsive disorder

BACKGROUND: Obsessive-compulsive disorder (OCD) is considered a heterogeneous disorder. One of the traditional approaches to subtype OCD is based on the predominance of obsessions, compulsions or both. Some studies suggest that the “predominantly obsessive” subtype of OCD may have poor outcome, whereas few other studies suggest that “mixed” OCD is associated with poor outcome. Therefore, it is not clear if the long-term course of “predominantly obsessive” subjects is different from those with “mixed” OCD. In the establishment of diagnostic validity of psychiatric conditions, differential course is an important validating factor. AIM: This study compares the 5-6 year course of the “predominantly obsessive” subtype with that of the “mixed” subtype of OCD with the objective of determining if the course of OCD differs according to subtypes and whether course could be a validating factor for subtyping OCD based on predominance of obsessions, compulsions or both. SETTING AND DESIGN: Tertiary hospital, institutional setting. The study has a retrospective cohort design. MATERIALS AND METHODS: Fifty-four subjects with “predominantly obsessions” and an equal number of the “mixed” subtype of OCD were recruited from the database of a specialty OCD clinic of a major psychiatric hospital. They were followed up after 5-6 years. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) checklist and severity rating scale was used for assessing OCD. The course of OCD was determined according to predefined criteria. STATISTICS: The Chi-square/Fisher's exact test and the independent samples “t” test were used to compare categorical and continuous variables, respectively. Correlations were tested using the Pearson's correlation analysis. RESULTS: Thirty-eight “predominantly obsessive” (70%) and 39 “mixed” (72%) OCD subjects could be traced and evaluated. The course of illness was similar in the two subtypes. A majority of the sample (72%) did not have clinical OCD at follow-up. CONCLUSIONS: “Predominantly obsessive” subjects have a course similar to those with “mixed” OCD. Clinically, it is reassuring to know that obsessive subjects do not have an unfavorable course as was suggested by some previous studies. In this sample, course did not validate the subtyping method employed, but it would be premature to conclude that the subtyping method employed is incorrect based on the course alone. Prospective study of the course in larger samples and neurobiological and family-genetic data may help further validation