Blastocyst-Inspired Hydrogels to Maintain Undifferentiation of Mouse Embryonic Stem Cells

Stem cell fate is determined by specific niches that provide multiple physical, chemical, and biological cues. However, the hierarchy or cascade of impact of these cues remains elusive due to their spatiotemporal complexity. Here, anisotropic silk protein nanofiber-based hydrogels with suitable cell adhesion capacity are developed to mimic the physical microenvironment inside the blastocele. The hydrogels enable mouse embryonic stem cells (mESCs) to maintain stemness in vitro in the absence of both leukemia inhibitory factor (LIF) and mouse embryonic fibroblasts (MEFs), two critical factors in the standard protocol for mESC maintenance. The mESCs on hydrogels can achieve superior pluripotency, genetic stability, developmental capacity, and germline transmission to those cultured with the standard protocol. Such biomaterials establish an improved dynamic niche through stimulating the secretion of autocrine factors and are sufficient to maintain the pluripotency and propagation of ESCs. The mESCs on hydrogels are distinct in their expression profiles and more resemble ESCs in vivo. The physical cues can thus initiate a self-sustaining stemness-maintaining program. In addition to providing a relatively simple and low-cost option for expansion and utility of ESCs in biological research and therapeutic applications, this biomimetic material helps gain more insights into the underpinnings of early mammalian embryogenesis.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

ACS nano - 15(2021), 9 vom: 28. Sept., Seite 14162-14173

Sprache:

Englisch

Beteiligte Personen:

Hang, Yingjie [VerfasserIn]
Ma, Xiaoliang [VerfasserIn]
Liu, Chunxiao [VerfasserIn]
Li, Siyuan [VerfasserIn]
Zhang, Sixuan [VerfasserIn]
Feng, Ruyan [VerfasserIn]
Shang, Qianwen [VerfasserIn]
Liu, Qi [VerfasserIn]
Ding, Zhaozhao [VerfasserIn]
Zhang, Xiaoyi [VerfasserIn]
Yu, Liyin [VerfasserIn]
Lu, Qiang [VerfasserIn]
Shao, Changshun [VerfasserIn]
Chen, Hong [VerfasserIn]
Shi, Yufang [VerfasserIn]
He, Jiuyang [VerfasserIn]
Kaplan, David L [VerfasserIn]

Links:

Volltext

Themen:

Embryonic stem cells
Hierarchy
Hydrogels
Journal Article
Physical cues
Pluripotency
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 08.10.2021

Date Revised 03.08.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acsnano.0c10468

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM330582410