The purpose of this study was to determine the functionality of the transplanted induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) in a rat model of cerebral ischemia with use of 18 F-FDG small-animal PET imaging. Methods: Middle cerebral artery occlusion was used to establish cerebral ischemia. Twenty-four male rats were randomly assigned to 1 of 3 groups: iPSC treatment, ESC treatment, and the control phosphate-buffered saline (PBS) injection. After neurologic function tests and baseline 18 F-FDG small-animal PET had been performed, 1.0 · 10 6 suspended iPSCs or ESCs were injected stereotactically into the left lateral ventricle. The treatment response was evaluated weekly by 18 F-FDG PET scans and neurologic function tests. Histologic analyses and autoradiographic imaging were performed 4 wk after stem cell transplantation. Results: Compared with the PBS injection group, higher 18 F-FDG accumulation in the ipsilateral cerebral infarction was observed in both the iPSC and the ESC treatment groups during the 4-wk period (P , 0.05). 18 F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in the iPSC treatment group. At 1 and 2 wk after stem cell transplantation, significant recovery of glucose metabolism was found in the ESC treatment group (P , 0.05) and then decreased gradually. The neurologic score in both stem celltreated groups was significantly lower than that in the PBS group, indicating functional improvement. Immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated close to the ischemic region, and most of the stem cells expressed protein markers for cells of interest. Conclusion: 18 F-FDG small-animal PET demonstrated metabolic recovery after iPSC and ESC transplantation in the rat model of cerebral ischemia. iPSCs could be considered a potentially better therapeutic approach than ESCs and are worthy of further translational investigation.
The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is unknown. Histopathologic studies revealed that pulmonary vasculature lesions similar to idiopathic pulmonary arterial hypertension (PAH) existed in CTEPH patients as well. It’s well-known that genetic predisposition plays an important role in the mechanism of PAH. So we hypothesized that PAH-causing gene mutation might exist in some CTEPH patients and act as a background to facilitate the development of CTEPH. In this study, we analyzed 7 PAH-causing genes including BMPR2, ACVRL1, ENG, SMAD9, CAV1, KCNK3, and CBLN2 in 49 CTEPH patients and 17 patients recovered from pulmonary embolism (PE) but without pulmonary hypertension(PH). The results showed that the nonsynonymous mutation rate in CTEPH patients is significantly higher than that in PE without PH patients (25 out of 49 (51%) CTEPH patients vs. 3 out of 17 PE without PH patients (18%); p = 0.022). Four CTEPH patients had the same point mutation in ACVRL1 exon 10 (c.1450C>G), a mutation approved to be associated with PH in a previous study. In addition, we identified two CTEPH associated SNPs (rs3739817 and rs55805125). Our results suggest that PAH-causing gene mutation might play an important role in the development of CTEPH.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.