Defined Culture Conditions Accelerate Small-molecule-assisted Neural Induction for the Production of Neural Progenitors from Human-induced Pluripotent Stem Cells

Patrick Walsh, Vincent Truong, Caitlin Hill, Nicolas D. Stoflet, Jessica Baden, Walter C. Low, Susan A. Keirstead, James R. Dutton, Ann M. Parr

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The use of defined conditions for derivation, maintenance, and differentiation of human-induced pluripotent stem cells (hiPSCs) provides a superior experimental platform to discover culture responses to differentiation cues and elucidate the basic requirements for cell differentiation and fate restriction. Adoption of defined systems for reprogramming, undifferentiated growth, and differentiation of hiPSCs was found to significantly influence early stage differentiation signaling requirements and temporal kinetics for the production of primitive neuroectoderm. The bone morphogenic protein receptor agonist LDN-193189 was found to be necessary and sufficient for neural induction in a monolayer system with landmark antigens paired box 6 and sex-determining region Y-box 1 appearing within 72 h. Preliminary evidence suggests this neuroepithelium was further differentiated to generate ventral spinal neural progenitors that produced electrophysiologically active neurons in vitro, maintaining viability posttransplantation in an immunocompromised host. Our findings support current developments in the field, demonstrating that adoption of defined reagents for the culture and manipulation of pluripotent stem cells is advantages in terms of simplification and acceleration of differentiation protocols, which will be critical for future clinical translation.

Original languageEnglish (US)
Pages (from-to)1890-1902
Number of pages13
JournalCell transplantation
Volume26
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Induced Pluripotent Stem Cells
Stem cells
Neural Plate
Pluripotent Stem Cells
Molecules
Immunocompromised Host
Cues
Cell Differentiation
Maintenance
Antigens
Neurons
Cell culture
Bone and Bones
Monolayers
Bone
Growth
Proteins
Kinetics
LDN 193189
In Vitro Techniques

Keywords

  • human-induced pluripotent stem cells
  • neural differentiation
  • ventral spinal neurons

Cite this

Defined Culture Conditions Accelerate Small-molecule-assisted Neural Induction for the Production of Neural Progenitors from Human-induced Pluripotent Stem Cells. / Walsh, Patrick; Truong, Vincent; Hill, Caitlin; Stoflet, Nicolas D.; Baden, Jessica; Low, Walter C.; Keirstead, Susan A.; Dutton, James R.; Parr, Ann M.

In: Cell transplantation, Vol. 26, No. 12, 01.12.2017, p. 1890-1902.

Research output: Contribution to journalArticle

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