Establishment of human iPSC-based models for the study and targeting of glioma initiating cells

Sancho‐Martinez, Ignacio; Nivet, Emmanuel; Xia, Yun; Hishida, Tomoaki; Aguirre, Aitor; Ocampo, Alejandro; Ma, Li; Morey, Robert; Krause, Manfred O.; Zembrzycki, Andreas; Ansorge, Olaf; Vazquez-Ferrer, Eric; Dubova, Ilir; Reddy, Pradeep; Lam, David; Hishida, Yuriko; Wu, Min-Zu; Esteban, Concepción Rodrı́guez; O’Leary, Dennis D.M.; Wahl, Geoffrey M.; Verma, Inder M.; Laurent, Louise C.; Belmonte, Juan Carlos Izpisúa

doi:10.1038/ncomms10743

Cited by 66 publications

(69 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[64] This study and future investigations to identify neural differentiation inducing-factors produced by stromal and stem cells in this co-culture system will enable developing novel protocols to generate neural cells as in this co-culture system but without using feeder cells and eliminate concerns regarding contamination of differentiated cells with stromal cells. Further, stem cell-derived neuronal and glial progenitors can serve as a unique model to study genetic modifications,[65] identify and target specific pathways,[66] and screen compounds for large scale drug discovery. [67]…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Stromal Cells-Induced Neural Differentiation of Mouse Embryonic Stem Cells

et al. 2016

View full text Add to dashboard Cite

Deriving specific neural cells from embryonic stem cells (ESCs) is a promising approach for cell replacement therapies of neurodegenerative diseases. When co-cultured with certain stromal cells, mouse ESCs (mESCs) differentiate efficiently to neural cells. In this study, a comprehensive gene and protein expression analysis of differentiating mESCs is performed over a two-week culture period to track temporal progression of cells from a pluripotent state to specific terminally-differentiated neural cells such as neurons, astrocytes, and oligodendrocytes. Expression levels of 26 genes consisting of marker genes for pluripotency, neural progenitors, and specific neuronal, astroglial, and oligodendrocytic cells are tracked using real time q-PCR. The time-course gene expression analysis of differentiating mESCs is combined with the hierarchal clustering and functional principal component analysis (FPCA) to elucidate the evolution of specific neural cells from mESCs at a molecular level. These statistical analyses identify three major gene clusters representing distinct phases of transition of stem cells from a pluripotent state to a terminally-differentiated neuronal or glial state. Temporal protein expression studies using immunohistochemistry demonstrate the generation of neural stem/progenitor cells and specific neural lineages and show a close agreement with the gene expression profiles of selected markers. Importantly, parallel gene and protein expression analysis elucidates long-term stability of certain proteins compared to those with a quick turnover. Describing the molecular regulation of neural cells commitment of mESCs due to stromal signaling will help identify major promoters of differentiation into specific cell types for use in cell replacement therapy applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of Stromal Cells-Induced Neural Differentiation of Mouse Embryonic Stem Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…There have been no reports of malignant transformation after transplantation in cases of mesenchymal stem cells or other somatic stem cells. In contrast, it has been reported that induced pluripotent stem cells (iPSCs) transformed into tumor stem cells when co-cultured with tumor cells [14]. Consequently, more considerations will be needed for pluripotent stem cell (ESCs/iPSCs)-derived cell products.…”

Section: Translational Medicinementioning

confidence: 89%

Regulatory Aspect of Pre-clinical Studies for Regenerative Medicine

Okura¹,

Matsuyama²

2016

Transl Med (sunnyvale)

View full text Add to dashboard Cite

Regenerative cell therapy is a discipline in youth, with only limited experience in clinical practice. Once manufacturing protocols of cells have been established in vitro studies, the manufactured cells were assigned as candidates for cell-based medicinal products. To judge whether the cell-based medicinal products manufactured according to the established protocols should be valuable for further development for clinical practice, pre-clinical studies shall be conducted. In construction of a pre-clinical study package for cell-based medicinal products, the preclinical study package used for chemical compounds will help a lot. The requirements and contents of the pre-clinical studies are classified into toxicity studies (general toxicity studies and special toxicity studies), pharmacological studies (primary pharmacodynamics studies and safety pharmacological studies), pharmacokinetic studies, formulation studies, and others. The pre-clinical studies for the cell-based medicinal products are conducted to evaluate and qualify the efficacy and safety of the candidates. No wonder there is an argument about the selection of assessment parameters in toxicity, pharmacological and pharmacokinetics studies for cell-based medicinal product, because it is well-known that the cell-based medicinal products are different in properties from chemical compounds. Besides parameters used in these studies, the assessment issues may be an assumable minimum consensus, and others should be added on a case-by-case basis, depending on the cell manufacturing processes. In anticipation of the approval as the cell-based medicinal products, the possible requirements should be discussed here in the development process of such products from the standpoint of regulatory science, especially focusing on those in pre-clinical studies.

show abstract

“…These cells can be transformed to glioma initiating cells by lentiviral transduction of oncogenes [128]. …”

Section: Preclinical Glioma Modelsmentioning

confidence: 99%

Glioma: experimental models and reality

et al. 2017

View full text Add to dashboard Cite

In theory, in vitro and in vivo models for human gliomas have great potential to not only enhance our understanding of glioma biology, but also to facilitate the development of novel treatment strategies for these tumors. For reliable prediction and validation of the effects of different therapeutic modalities, however, glioma models need to comply with specific and more strict demands than other models of cancer, and these demands are directly related to the combination of genetic aberrations and the specific brain micro-environment gliomas grow in. This review starts with a brief introduction on the pathological and molecular characteristics of gliomas, followed by an overview of the models that have been used in the last decades in glioma research. Next, we will discuss how these models may play a role in better understanding glioma development and especially in how they can aid in the design and optimization of novel therapies. The strengths and weaknesses of the different models will be discussed in light of genotypic, phenotypic and metabolic characteristics of human gliomas. The last part of this review provides some examples of how therapy experiments using glioma models can lead to deceptive results when such characteristics are not properly taken into account.

show abstract

Establishment of human iPSC-based models for the study and targeting of glioma initiating cells

Cited by 66 publications

References 55 publications

Molecular Analysis of Stromal Cells-Induced Neural Differentiation of Mouse Embryonic Stem Cells

Molecular Analysis of Stromal Cells-Induced Neural Differentiation of Mouse Embryonic Stem Cells

Regulatory Aspect of Pre-clinical Studies for Regenerative Medicine

Glioma: experimental models and reality

Contact Info

Product

Resources

About