Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells

Nizzardo, Monica; Simone, Carla; Falcone, Marika; Locatelli, Federica; Riboldi, Giulietta; Comi, Giacomo P.; Corti, Stefania

doi:10.1007/s00018-010-0463-y

Cited by 68 publications

(38 citation statements)

References 84 publications

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“…So far, several studies have addressed therapeutic potential of stem cells in regeneration of motor neuron-related disorders [27,28]. Among different types of stem cells, mesenchymal stem cells (MSCs) with their self renewal property and immunomodulatory capacity are the focus of interest among scientists.…”

Section: Discussionmentioning

confidence: 99%

Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two- and Three-Dimensional Culture Systems

Faghihi

Mirzaei

et al. 2015

Mol Neurobiol

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Many people worldwide suffer from motor neuron-related disorders such as amyotrophic lateral sclerosis and spinal cord injuries. Recently, several attempts have been made to recruit stem cells to modulate disease progression in ALS and also regenerate spinal cord injuries. Chorion-derived mesenchymal stem cells (C-MSCs), used to be discarded as postpartum medically waste product, currently represent a class of cells with self renewal property and immunomodulatory capacity. These cells are able to differentiate into mesodermal and nonmesodermal lineages such as neural cells. On the other hand, gelatin, as a simply denatured collagen, is a suitable substrate for cell adhesion and differentiation. It has been shown that electrospinning of scaffolds into fibrous structure better resembles the physiological microenvironment in comparison with two-dimensional (2D) culture system. Since there is no report on potential of human chorion-derived MSCs to differentiate into motor neuron cells in two- and three-dimensional (3D) culture systems, we set out to determine the effect of retinoic acid (RA) and sonic hedgehog (Shh) on differentiation of human C-MSCs into motor neuron-like cells cultured on tissue culture plates (2D) and electrospun nanofibrous gelatin scaffold (3D).

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Section: Discussionmentioning

confidence: 99%

Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two- and Three-Dimensional Culture Systems

Faghihi

Mirzaei

et al. 2015

Mol Neurobiol

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“…2a), choline acetyltransferease (ChAT) that catalyses synthesis of acetylcholine, a neuron transmitter and is found exclusively in the MNs in the ventral spinal cord 23 ( Fig. 2f), and SMI-32, a nonphosphorylated neurofilament marker that stains MNs in the spinal cord 24,25 ( Supplementary Fig. 2b).…”

Section: Resultsmentioning

confidence: 99%

High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1

et al. 2014

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Efficient derivation of large-scale motor neurons (MNs) from human pluripotent stem cells is central to the understanding of MN development, modelling of MN disorders in vitro and development of cell-replacement therapies. Here we develop a method for rapid (20 days) and highly efficient (B70%) differentiation of mature and functional MNs from human pluripotent stem cells by tightly modulating neural patterning temporally at a previously undefined primitive neural progenitor stage. This method also allows high-yield (4250%) MN production in chemically defined adherent cultures. Furthermore, we show that Islet-1 is essential for formation of mature and functional human MNs, but, unlike its mouse counterpart, does not regulate cell survival or suppress the V2a interneuron fate. Together, our discoveries improve the strategy for MN derivation, advance our understanding of human neural specification and MN development, and provide invaluable tools for human developmental studies, drug discovery and regenerative medicine.

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“…Even though iPSCs have been differentiated into a number of cell types including cardiomyocytes [129][130][131][132][133], neurons [134,135], blood [133,136,137] and pancreatic cells [137,138], purities over 95% have not been reported and isolating these cells from a heterogeneous cell population is difficult. Furthermore, ESC-/iPSC-derived cells are mostly immature and whether their stage will affect their clinical performance remains to be investigated in a celland disease-specific manner [108].…”

Section: Clinical Potential Of Pluripotent Stem Cellsmentioning

confidence: 99%

Pluripotent Stem Cells and Their Dynamic Niche

Reinwald¹,

Bratt²,

Haj³

2016

Pluripotent Stem Cells - From the Bench to the Clinic

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Cell-seeded implants are a regenerative medicine strategy that aims to replace injured tissue and restore tissue function. Pluripotent stem cells are promising cell candidates for the development of regenerative medicine therapies as they have the ability to selfrenew and commit towards numerous cell types. In vivo, stem cells reside in a dynamic niche, a stem cell-specific microenvironment that possesses chemical, biological and mechanical cues, which drive the stem cell fate and renewal. The connection between stem cells and their niche is a two-way relationship consisting of both cell-cell interaction and cell-extracellular matrix (ECM) interactions. An alternative regenerative medicine approach is the manipulation of the stem cell microenvironment. Hence, novel strategies have been developed including 3D biomaterials and bioreactor technologies providing topographical, chemical and mechanical cues to recreate the stem cell niche. Understanding the mechanisms controlling stem cell fate and the dynamic nature of the stem cell niche will enable researchers to replicate this stem cell-specific microenvironment, and therefore, harness and control the valuable attributes which stem cells possess. This chapter elucidates the importance of pluripotent stem cells and their dynamic niche in regenerative medicine. It further presents novel strategies to replicate chemical, topographical and mechanical stimuli which are essential for the regulation of stem cell fate and hence tissue regeneration.

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Human motor neuron generation from embryonic stem cells and induced pluripotent stem cells

Cited by 68 publications

References 84 publications

Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two- and Three-Dimensional Culture Systems

Differentiation Potential of Human Chorion-Derived Mesenchymal Stem Cells into Motor Neuron-Like Cells in Two- and Three-Dimensional Culture Systems

High-efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1

Pluripotent Stem Cells and Their Dynamic Niche

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