Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington's Disease

Fink, Kyle D.; Crane, Andrew T.; Lévèque, Xavier; Dues, Dylan J.; Huffman, Lucas D.; Moore, Allison C.; Story, Darren; Dejonge, R; Antcliff, Aaron; Starski, Phillip; Lu, Ming; Lescaudron, Laurent; Rossignol, Julien; Dunbar, Gary

doi:10.5966/sctm.2013-0151

Cited by 30 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, establishing this patient-derived model requires only minimal technical and financial resources, and is ideally suited for smaller laboratories. In addition, should the need arise in follow-up experiments, patient fibroblasts can be transformed into IPSCs that can be differentiated into neuronal lineages (86). …”

Section: Discussionmentioning

confidence: 99%

Coordinated Messenger RNA/MicroRNA Changes in Fibroblasts of Patients with Major Depression

Garbett

Vereczkei

Kálmán

et al. 2015

Biological Psychiatry

View full text Add to dashboard Cite

Background Peripheral biomarkers for major psychiatric disorders have been an elusive target for the last half a century. Dermal fibroblasts are a simple, relevant, and much underutilized model for studying molecular processes of patients with affective disorders as they share considerable similarity of signal transduction with neuronal tissue. Methods Cultured dermal fibroblast samples from patients with Major Depressive Disorder (MDD) and matched controls (CNTR) (n=16 pairs, 32 samples) were assayed for genome wide mRNA expression using microarrays. In addition, a simultaneous qPCR-based assessment of >1,000 miRNA species was performed. Finally, to test the relationship between the mRNA-miRNA expression changes, the two datasets were correlated with each other. Results Our data revealed that MDD fibroblasts, when compared to matched controls, showed a strong mRNA gene expression pattern change in multiple molecular pathways, including cell-to-cell communication, innate/adaptive immunity and cell proliferation. Furthermore, the same patient fibroblasts showed altered expression of a distinct panel of 38 miRNAs, which putatively targeted many of the differentially expressed mRNAs. The miRNA-mRNA expression changes appeared to be functionally connected, as the majority of the miRNA and mRNA changes were in the opposite direction. Conclusions Our data suggest that a combined miRNA-mRNA assessments are informative about the disease process, and that analyses of dermal fibroblasts might lead to the discovery of promising peripheral biomarkers of MDD, which could be potentially used to aid the diagnosis and allow mechanistic testing of disturbed molecular pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

Coordinated Messenger RNA/MicroRNA Changes in Fibroblasts of Patients with Major Depression

Garbett

Vereczkei

Kálmán

et al. 2015

Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…15 Currently, iPSC research is focused on numerous diseases, especially genetic diseases such as familiar Alzheimer's disease, Huntington's disease, and Parkinson's disease. [16][17][18] In this study, we developed a simple, noninvasive, and acceptable method to generate iPSCs from renal tubular cells, thus providing an ideal cell source for iPSC generation. In contrast to other tissues sources such as skin and blood, which require a traumatic harvesting procedure, urine was easily accessible and was with minimum effort.…”

Section: Discussionmentioning

confidence: 99%

Generation of induced pluripotent stem cells from renal tubular cells of a patient with Alport syndrome

Chen¹,

Huang²,

Yu³

et al. 2015

IJNRD

View full text Add to dashboard Cite

Alport syndrome (AS) is a hereditary disease that leads to kidney failure and is caused by mutations in the COL4A3, COL4A4, and COL4A5 genes that lead to the absence of collagen α3α4α5 (IV) networks in the mature kidney glomerular basement membrane. Approximately 80% of AS is X-linked because of mutations in COL4A5, the gene encoding the alpha 5 chain of type IV collagen. To investigate the pathogenesis of AS at the genetic level, we generated induced pluripotent stem cells (iPSCs) from renal tubular cells of a patient with AS. The successful iPSC generation laid the foundation to master the repair of the COL4A5 gene and to evaluate the differentiation of iPSC into Sertoli cells and the accompanying epigenetic changes at each stage. The generation of iPSCs from AS patients not only confirms that iPSCs could be generated from renal tubular cells, but also provides a novel type of genetic therapy for AS patients. In this study, we generated iPSCs from renal tubular cells via ectopic expression of four transcription factors (Oct4, Sox2, c-myc, and Klf4). According to the human embryonic stem cell (hESC) charter, iPSC formation was confirmed by comparatively analyzing hESC markers via colony morphology, immunohistochemistry, qRT-PCR, flow cytometry, gene expression profiling of the three germ layers, and karyotyping. Our results demonstrated that iPSCs were similar to hESCs with regard to morphology, proliferation, hESC-specific surface marker expression, and differentiation into the cell types of the three germ layers. The efficient generation of iPSCs from the renal tubular cells of an AS patient would provide a novel model to investigate the mechanisms underlying AS and to develop new treatments for AS.

show abstract

“…Neurogenic differentiating iPSCs follow similar developmental principles as hESC‐derived neurons, although the neural differentiation efficiency can differ between different iPSC lines . Targeted differentiation of iPSCs toward neuronal subtypes has been achieved by various research groups, using different approaches to generate a variety of neuronal cells including medium spiny neurons, dopaminergic neurons, motor neurons, nociceptors, and pyramidal cortical neurons . Furthermore, it was shown that these neuronally differentiated cells are capable of repeated action potential firing, suggesting advanced maturation .…”

Section: Induced Pluripotent Stem Cells As a Therapy In Strokementioning

confidence: 99%

Stem Cell‐Based Therapies for Ischemic Stroke: Preclinical Results and the Potential of Imaging‐Assisted Evaluation of Donor Cell Fate and Mechanisms of Brain Regeneration

Gervois

Wolfs

Ratajczak

et al. 2016

Medicinal Research Reviews

View full text Add to dashboard Cite

Stroke is the second most common cause of death and is a major cause of permanent disability. Given the current demographic trend of an ageing population and associated increased risk, the prevalence of and socioeconomic burden caused by stroke will continue to rise. Current therapies are unable to sufficiently ameliorate the disease outcome and are not applicable to all patients. Therefore, strategies such as cell-based therapies with mesenchymal stem cell (MSC) or induced pluripotent stem cell (iPSC) pave the way for new treatment options for stroke. These cells showed great preclinical promise despite the fact that the precise mechanism of action and the optimal administration route are unknown. To gain dynamic insights into the underlying repair processes after stem cell engraftment, noninvasive imaging modalities were developed to provide detailed spatial and functional information on the donor cell fate and host microenvironment. This review will focus on MSCs and iPSCs as types of widely used stem cell sources in current (bio)medical research and compare their efficacy and potential to ameliorate the disease outcome in animal stroke models. In addition, novel noninvasive imaging strategies allowing temporospatial in vivo tracking of transplanted cells and coinciding evaluation of neuronal repair following stroke will be discussed.

show abstract

Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington's Disease

Cited by 30 publications

References 45 publications

Coordinated Messenger RNA/MicroRNA Changes in Fibroblasts of Patients with Major Depression

Coordinated Messenger RNA/MicroRNA Changes in Fibroblasts of Patients with Major Depression

Generation of induced pluripotent stem cells from renal tubular cells of a patient with Alport syndrome

Stem Cell‐Based Therapies for Ischemic Stroke: Preclinical Results and the Potential of Imaging‐Assisted Evaluation of Donor Cell Fate and Mechanisms of Brain Regeneration

Contact Info

Product

Resources

About