Modeling human skeletal development using human pluripotent stem cells-Reference-Cited by-同舟云学术

Modeling human skeletal development using human pluripotent stem cells

Published:2023-05 Issue:19 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Lamandé Shireen R.¹²³^ORCID,Ng Elizabeth S.¹²³,Cameron Trevor L.¹^ORCID,Kung Louise H. W.¹^ORCID,Sampurno Lisa¹,Rowley Lynn¹^ORCID,Lilianty Jinia¹²^ORCID,Patria Yudha Nur¹²⁴^ORCID,Stenta Tayla¹^ORCID,Hanssen Eric⁵^ORCID,Bell Katrina M.¹,Saxena Ritika¹²^ORCID,Stok Kathryn S.⁶,Stanley Edouard G.¹²³^ORCID,Elefanty Andrew G.¹²³^ORCID,Bateman John F.¹²^ORCID

Affiliation:

1. Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia

2. Department of Paediatrics, University of Melbourne, Parkville, VIC 3052, Australia

3. The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Murdoch Children’s Research Institute, Parkville, VIC 3052, Australia

4. Department of Child Health, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia

5. Ian Holmes Imaging Center and Department of Biochemistry and Pharmacology, Bio21 Institute, University of Melbourne, Parkville, VIC 3010, Australia

6. Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia

Abstract

Chondrocytes and osteoblasts differentiated from induced pluripotent stem cells (iPSCs) will provide insights into skeletal development and genetic skeletal disorders and will generate cells for regenerative medicine applications. Here, we describe a method that directs iPSC-derived sclerotome to chondroprogenitors in 3D pellet culture then to articular chondrocytes or, alternatively, along the growth plate cartilage pathway to become hypertrophic chondrocytes that can transition to osteoblasts. Osteogenic organoids deposit and mineralize a collagen I extracellular matrix (ECM), mirroring in vivo endochondral bone formation. We have identified gene expression signatures at key developmental stages including chondrocyte maturation, hypertrophy, and transition to osteoblasts and show that this system can be used to model genetic cartilage and bone disorders.

Funder

DHAC | National Health and Medical Research Council

Stem Cells Australia

Stafford Fox Medical Research Foundation

Novo Nordisk Fonden

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2211510120

Reference98 articles.