Experimental and clinical studies are progressing simultaneously to investigate the mechanisms and efficacy of progenitor cell treatment after an acute myocardial infarction and in chronic congestive heart failure. Multipotent progenitor cells appear to be capable of improving cardiac perfusion and/or function; however, the mechanisms still are unclear, and the issue of whether or not trans-differentiation occurs remains unsettled. Both experimentally and clinically, cells originating from different tissues have been shown capable of restoring cardiac function, but more recently multiple groups have identified resident cardiac progenitor cells that seem to participate in regenerating the heart after injury. Clinically, cells originating from blood or bone marrow have been proven to be safe whereas injection of skeletal myoblasts has been associated with the occurrence of ventricular arrhythmias. Myoblasts can transform into rapidly beating myotubes; however, thus far convincing evidence for electro-mechanical coupling between myoblasts and cardiomyocytes is lacking. Moving forward, mechanistic studies will benefit from the use of genetic markers and Cre/lox reporter systems that are less prone to misinterpretation than fluorescent antibodies, and a more convincing answer regarding therapeutic efficacy will come from adequately powered randomized placebo controlled trials. Gene Therapy (2006) 13, 659-671.

Background Transplantation of mesenchymal stem cells has created enormous opportunities as a potential treatment for various diseases including neurodegenerative diseases. Given current techniques, such as Hoechst labeling, have safety and leakage issues, our study focused, as a proof-of-concept, on a new dendrimer-based technique for labeling these stem cells to ensure their efficacy and safety following transplantation into the brain of a healthy mice. Methods and results The bone marrow-derived mesenchymal stem cells (BM-MSCs) were labeled using polyaminoamine (PAMAM) dendrimers following which their stemness based on their proliferation and differentiation ability were analyzed by gold standard methods. These labeled BM-MSCs were transplanted into the striatum of C57BL/6J mice and were tracked using in vivo imaging system (IVIS) and analyzed using tissue imaging, 2 weeks after transplantation. Our results showed that the dendrimer-labeled BM-MSCs were able to successfully maintain their stemness and were tracked in vivo following transplantation. Unlike Hoechst, we did not find the dendrimers to be leaking out of the cells and were very specific to the cells that up took the dendrimers. Moreover, no adverse events were found in the transplanted animals proving that this is a safer method. Conclusions Labeling BM-MSCs using fluorescently tagged PAMAM dendrimers can be used as a potentially safe and efficient method for labeling cells, particularly stem cells, in vitro and in vivo following transplantation in rodents.

Parkinson’s disease (PD) is a neurodegenerative disease with loss of dopaminergic neurons. PD has genetic and epigenetic influences that determine specific changes in the brain. Epigenetic changes result in defective methylation of genes leading to differential gene-expression causing PD. This review provides an overview of stem cell transplantations as potential therapies for PD, with a focus on the epigenetic changes, prior or following transplantation. To date, no reports have addressed epigenetic alterations following stem cell transplantation into the PD brain. Given the potential for affecting the efficacy of stem cell therapy, increased attention needs to be given to the epigenetic processes that occur during stem cell culture and transplantation to maximize the therapeutic potential of stem cells to PD.

A major drawback of current stroke treatment strategies (such as the use of tPA) includes time sensitivity to achieve maximum therapeutic efficacy. Alternative treatments include less time-sensitive approaches and utilize in vivo reprogramming of resident reactive astrocytes to repopulate the lost neurons in sufficient numbers. In this study, we tested whether a transcription factor, hSOX2, when expressed under a glial cell-specific GFAP promoter, could sufficiently reprogram astrocytes in and around the infarct to enhance their differentiation into neurons. To achieve delivery of the hSOX2 gene, we utilize PAMAM dendrimers, which are nanomolecules with a well-established capacity of delivering drugs/ large biomolecules to the brain across the BBB and confer intrinsic anti-inflammatory properties. Dendrimers are comprised of an interior dendritic structure with modifiable sizes, and an exterior surface with functional surface groups. The G4 PAMAM dendrimers used in this study has 10% of the surface covered with amine groups and 90% of the surface covered with hydroxyl groups (G4-90/10). These dendrimers are less toxic and readily form complexes with plasmids up to 14 kb in size (dendriplex) and successfully deliver cargo in vitro and in vivo . Four days following stroke inductions in Sprague Dawley rats via MCAo, the hSOX2 dendriplex was injected into the ipsilateral corpus callosum. A battery of behavior tests, such as cylinder and ladder tasks, were used to assess motor abilities of the treated and untreated stroked and sham-operated control rats. Moreover, the animals underwent In vivo Imaging System to confirm the presence of dendriplex in the brain. Five weeks following the injections, the brains were collected and processed, using immunohistochemistry, to detect the complex and measure the amount of hSOX2 gene expression. The size of the brain infarct was measured using the conventional H&E staining. Our results indicated that the dendrimers were able to deliver the hSOX2 gene to the stroke brain and this significantly reduced motor deficits, relative to untreated stroked rats. These results indicated that PAMAM dendrimers effectively deliver genes into the brain and that the hSOX2 gene can successfully reduce motor deficits following stroke.