Abstract
Organoids are becoming particularly popular in modeling diseases that are difficult to reproduce in animals, due to anatomical differences in the structure of a given organ. Thus, they are a bridge between the in vitro and in vivo models. Human midbrain is one of the structures that is currently being intensively reproduced in organoids for modeling Parkinson’s disease (PD). Thanks to three-dimensional (3D) architecture and the use of induced pluripotent stem cells (iPSCs) differentiation into organoids, it has been possible to recapitulate a complicated network of dopaminergic neurons. In this work, we present the first organoid model for an idiopathic form of PD. iPSCs were generated from peripheral blood mononuclear cells of healthy volunteers and patients with the idiopathic form of PD by transduction with Sendai viral vector. iPSCs were differentiated into a large multicellular organoid-like structure. The mature organoids displayed expression of neuronal early and late markers. Interestingly, we observed statistical differences in the expression levels of LIM homeobox transcription factor alpha (early) and tyrosine hydroxylase (late) markers between organoids from PD patient and healthy volunteer. The obtained results show immense potential for the application of 3D human organoids in studying the neurodegenerative disease and modeling cellular interactions within the human brain.
Highlights
The generation of the induced pluripotent stem cells by Yamanaka’s group was a milestone for regenerative medicine
Yamanaka discovered that factors that are responsible for the parental state of embryonic stem cells (ES) might confer pluripotency in somatic cells. 24 genes that are responsible for pluripotency in early embryos and ES cells were selected as candidates
We present, for the first time, a model of midbrain organoids that is based on induced pluripotent stem cells (iPSCs) obtained from Parkinson’s disease (PD) patient with an idiopathic form of the disease
Summary
The generation of the induced pluripotent stem cells (iPSCs) by Yamanaka’s group was a milestone for regenerative medicine. Yamanaka discovered that factors that are responsible for the parental state of embryonic stem cells (ES) might confer pluripotency in somatic cells. Four factors were discovered to be necessary and sufficient for the transformation of somatic cells into iPSCs in a process, called reprogramming. Those factors are Sox, Oct3/4, Klf, and c-Myc [1,2]. IPSCs can be generated from somatic cells, which allows for studies using patients derived cells. IPSCs opened up the possibility of studying diseases with unknown pathogenesis. Another advantage of iPSCs is the elimination of ethical concerns regarding embryonic stem cells (ESCs) utilization
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