Three-dimensional hyaluronic acid hydrogel-based models for in vitro human iPSC-derived NPC culture and differentiation

Shaohua Wu, Ranjie Xu, Bin Duan, Peng Jiang

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Human induced pluripotent stem cell-derived neural progenitor cells (hiPSC-NPCs) are considered as a promising cell source for transplantation and have been used for organoid fabrication to recapitulate central nervous system (CNS) diseases in vitro. The establishment of a three-dimensional (3D) in vitro model with hiPSC-NPCs and control of their differentiation are significantly critical for understanding biological processes and CNS disease and regeneration. Here we implemented 3D methacrylated hyaluronic acid (Me-HA) hydrogels with encapsulation of hiPSC-NPCs as in vitro culture models and further investigated the role of the hydrogel rigidity in the cell behavior of hiPSC-NPCs. We first encapsulated single dispersive hiPSC-NPCs within both soft and stiff Me-HA hydrogels and found that hiPSC-NPCs gradually self-assembled and aggregated to form 3D spheroids. Then, the hiPSC-NPCs were laden into Me-HA hydrogels in the form of spheroids to evaluate their spontaneous differentiation in response to hydrogel rigidity. The soft Me-HA hydrogel-encapsulated hiPSC-NPCs displayed robust neurite outgrowth and showed high levels of spontaneous neural differentiation. We further encapsulated Down Syndrome (DS) patient-specific hiPSC-derived NPC (DS-NPC) spheroids within our hydrogels. DS-NPCs retained excellent cell viability in both soft and stiff Me-HA hydrogels. Similarly, soft hydrogels promoted neural differentiation of DS-NPCs by significantly upregulating neural maturation markers. This study demonstrates that the soft matrix promotes neural differentiation of hiPSC-NPCs and HA-based hydrogels with hiPSC-NPCs or DS-NPCs are effective 3D models for a CNS disease study.

Original languageEnglish (US)
Pages (from-to)3870-3878
Number of pages9
JournalJournal of Materials Chemistry B
Volume5
Issue number21
DOIs
StatePublished - Jan 1 2017

Fingerprint

Hyaluronic acid
Induced Pluripotent Stem Cells
Hydrogel
Hyaluronic Acid
Stem cells
Cell culture
Hydrogels
Stem Cells
Down Syndrome
Neurology
Central Nervous System Diseases
Rigidity
In Vitro Techniques
Organoids
Biological Phenomena
Cell Transplantation
Encapsulation
Regeneration
Cell Survival
Cells

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

Cite this

Three-dimensional hyaluronic acid hydrogel-based models for in vitro human iPSC-derived NPC culture and differentiation. / Wu, Shaohua; Xu, Ranjie; Duan, Bin; Jiang, Peng.

In: Journal of Materials Chemistry B, Vol. 5, No. 21, 01.01.2017, p. 3870-3878.

Research output: Contribution to journalArticle

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