Karolinska Institutet Human Embryonic Stem Cell Bank

Main, Heather; Hedenskog, Mona; Acharya, Ganesh; Hovatta, Outi; Lanner, Fredrik

doi:10.1016/j.scr.2020.101810

Cited by 13 publications

(14 citation statements)

References 6 publications

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“…1A ). For the neural induction of undifferentiated HS360 hESCs (Main et al, 2020; Ström et al, 2010), we used LDN193189, SB431542 and XAV939 (LSX). This LSX cocktail antagonizes the BMP, TGFβ and WNT signalling pathways to drive cells to anterior neuroectoderm (Cakir et al, 2019; Major et al, 2016; Ohashi et al, 2018; Tchieu et al, 2017).…”

Section: Resultsmentioning

confidence: 99%

A multi-omics approach to visualize early neuronal differentiation in 4D

Samara

Spildrejorde

Sharma

et al. 2022

Preprint

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Neuronal differentiation of pluripotent stem cells is an established method to study physiology, disease and medication safety. However, the sequence of events in human neuronal differentiation and the ability of in vitro models to recapitulate early brain development are poorly understood. We developed a protocol optimized for the study of early human brain development and neuropharmacological applications. We comprehensively characterized gene expression and epigenetic profiles at four timepoints, as the cells differentiate from embryonic stem cells towards a heterogenous population of progenitors, immature and mature neurons bearing telencephalic signatures. A multi-omics roadmap of neuronal differentiation, combined with searchable interactive gene analysis tools, allows for extensive exploration of early neuronal development and the effect of medications.

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Section: Resultsmentioning

confidence: 99%

A multi-omics approach to visualize early neuronal differentiation in 4D

Samara

Spildrejorde

Sharma

et al. 2022

Preprint

Self Cite

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“…Laminin 521 is a xeno-free defined surface that is suitable for hESC culture and is also used for the directed differentiation of hESCs into several cell types, for example, retinal pigment epithelial cells, hepatic cells, and dopaminergic neurons [ 2 , 3 , 4 , 27 ]. We used it as a derivation and culture substrate based on its availability in cGMP quality before the recently published reports, where the derivation of clinical-grade hESC lines on laminin 521 was described [ 32 , 33 ]. Our first experiments with laminin 521 confirmed its suitability for the derivation as we were able to derive and culture four research-grade hESC lines on this surface (data not shown).…”

Section: Discussionmentioning

confidence: 99%

The Manufacture of Xeno- and Feeder-Free Clinical-Grade Human Embryonic Stem Cell Lines: First Step for Cell Therapy

Souralová

Řeháková

Ješeta

et al. 2022

IJMS

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Human embryonic stem cells (hESCs) are increasingly used in clinical trials as they can change the outcome of treatment for many human diseases. They are used as a starting material for further differentiation into specific cell types and to achieve the desirable result of the cell therapy; thus, the quality of hESCs has to be taken into account. Therefore, current good manufacturing practice (cGMP) has to be implemented in the transport of embryos, derivation of inner cell mass to xeno-free, feeder-free and defined hESC culture, and cell freezing. The in-depth characterization of hESC lines focused on safety, pluripotency, differentiation potential and genetic background has to complement this process. In this paper, we show the derivation of three clinical-grade hESC lines, MUCG01, MUCG02, and MUCG03, following these criteria. We developed and validated the system for the manufacture of xeno-free and feeder-free clinical-grade hESC lines that present high-quality starting material suitable for cell therapy according to cGMP.

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“…Human ESC lines (HS980 and HS401) 67 were provided by Drs. Outi Hovatta and Fredrik Lanner (Karolinska Institutet).…”

Section: Methodsmentioning

confidence: 99%

Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery

et al. 2022

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Stem cell therapies for Parkinson’s disease (PD) have entered first-in-human clinical trials using a set of technically related methods to produce mesencephalic dopamine (mDA) neurons from human pluripotent stem cells (hPSCs). Here, we outline an approach for high-yield derivation of mDA neurons that principally differs from alternative technologies by utilizing retinoic acid (RA) signaling, instead of WNT and FGF8 signaling, to specify mesencephalic fate. Unlike most morphogen signals, where precise concentration determines cell fate, it is the duration of RA exposure that is the key-parameter for mesencephalic specification. This concentration-insensitive patterning approach provides robustness and reduces the need for protocol-adjustments between hPSC-lines. RA-specified progenitors promptly differentiate into functional mDA neurons in vitro, and successfully engraft and relieve motor deficits after transplantation in a rat PD model. Our study provides a potential alternative route for cell therapy and disease modelling that due to its robustness could be particularly expedient when use of autologous- or immunologically matched cells is considered.

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Karolinska Institutet Human Embryonic Stem Cell Bank

Cited by 13 publications

References 6 publications

A multi-omics approach to visualize early neuronal differentiation in 4D

A multi-omics approach to visualize early neuronal differentiation in 4D

The Manufacture of Xeno- and Feeder-Free Clinical-Grade Human Embryonic Stem Cell Lines: First Step for Cell Therapy

Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery

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