Complex Tissue and Disease Modeling using hiPSCs

Abstract

Defined genetic models based on human pluripotent stem cells have opened new avenues for understanding disease mechanisms and drug screening. Many of these models assume cell-autonomous mechanisms of disease but it is possible that disease phenotypes or drug responses will only be evident if all cellular and extracellular components of a tissue are present and functionally mature. To derive optimal benefit from such models, complex multicellular structures with vascular components that mimic tissue niches will thus likely be necessary. Here we consider emerging research creating human tissue mimics and provide some recommendations for moving the field forward.

Dishing out mini-brains: Current progress and future prospects in brain organoid research

“…However, the field of developmental organoid research is currently booming (Fatehullah et al, 2016, Huch and Koo, 2015, Passier et al, 2016, Suzuki and Vanderhaeghen, 2015, Yin et al, 2016) and we can expect a surge of studies in the near future.…”

Evaluating cell reprogramming, differentiation and conversion technologies in neuroscience

“…The generation of 3D cerebral organoids from human pluripotent stem cells has been recently proposed as a means to overcome these limitations and to also recapitulate aspects of early human brain cortical development that still appear inaccessible through direct induced neuron conversion paradigms 36 . Although early results seem promising for the study of neural progenitor migration and cortical expansion, current hurdles include a broad variety of floating aggregates that contain notable degree of heterogeneity of cell types as well as a lack of nutritious support for cells located in the centre of these aggregates 188,189 . Reduction of variation through a higher degree of structural control, together with live imaging of specific migrating progenitors, will be essential to promote a better understanding of the potential applications for the organoid technology and will provide a unique opportunity to study human development that is otherwise inaccessible.…”

Stem Cells: A Renaissance in Human Biology Research

“…Despite recent exciting developments, it is only the beginning for complex tissue formation and disease modeling using hPSCs (Passier et al, 2016). There are still several challenges to be solved for hPSC-derived organoids: (1) the majority, if not all, of organoids differentiated from hPSC contain a mixture of other unwanted cell types that can potentially interfere with the interpretation of downstream assays; (2) hPSC differentiation mostly generates fetal cell types (Hrvatin et al, 2014;van den Berg et al, 2015), which also seems to be the case for hPSC-derived organoids (Dye et al, 2015;Finkbeiner et al, 2015;Takasato et al, 2015); and (3) the key to success of generation of organoids from hPSCs is the understanding of the successive signaling pathways controlling the whole differentiation process, the knowledge of which is primarily derived from animal studies and, in some cases, are not directly applicable for hPSC differentiation.…”