Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

Ok Hee Jeon, Leelamma M. Panicker, Qiaozhi Lu, Jeremy J. Chae, Ricardo A. Feldman, Jennifer Hartt Elisseeff

Research output: Contribution to journalArticle

Abstract

Bone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA-PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5% w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.

Original languageEnglish (US)
Article number26761
JournalScientific Reports
Volume6
DOIs
StatePublished - May 26 2016

Fingerprint

Bone Regeneration
Biocompatible Materials
Osteoclasts
Osteoblasts
Induced Pluripotent Stem Cells
Bone and Bones
Macrophages
Bone Substitutes
Immunomodulation
Durapatite
Mesenchymal Stromal Cells
Osteogenesis
Rodentia
polylactic acid-polyglycolic acid copolymer

ASJC Scopus subject areas

  • General

Cite this

Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. / Jeon, Ok Hee; Panicker, Leelamma M.; Lu, Qiaozhi; Chae, Jeremy J.; Feldman, Ricardo A.; Elisseeff, Jennifer Hartt.

In: Scientific Reports, Vol. 6, 26761, 26.05.2016.

Research output: Contribution to journalArticle

Jeon, Ok Hee ; Panicker, Leelamma M. ; Lu, Qiaozhi ; Chae, Jeremy J. ; Feldman, Ricardo A. ; Elisseeff, Jennifer Hartt. / Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials. In: Scientific Reports. 2016 ; Vol. 6.
@article{6e100fe59cbe4e42a8cd65f8282cf6ae,
title = "Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials",
abstract = "Bone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA-PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5{\%} w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.",
author = "Jeon, {Ok Hee} and Panicker, {Leelamma M.} and Qiaozhi Lu and Chae, {Jeremy J.} and Feldman, {Ricardo A.} and Elisseeff, {Jennifer Hartt}",
year = "2016",
month = "5",
day = "26",
doi = "10.1038/srep26761",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Human iPSC-derived osteoblasts and osteoclasts together promote bone regeneration in 3D biomaterials

AU - Jeon, Ok Hee

AU - Panicker, Leelamma M.

AU - Lu, Qiaozhi

AU - Chae, Jeremy J.

AU - Feldman, Ricardo A.

AU - Elisseeff, Jennifer Hartt

PY - 2016/5/26

Y1 - 2016/5/26

N2 - Bone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA-PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5% w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.

AB - Bone substitutes can be designed to replicate physiological structure and function by creating a microenvironment that supports crosstalk between bone and immune cells found in the native tissue, specifically osteoblasts and osteoclasts. Human induced pluripotent stem cells (hiPSC) represent a powerful tool for bone regeneration because they are a source of patient-specific cells that can differentiate into all specialized cell types residing in bone. We show that osteoblasts and osteoclasts can be differentiated from hiPSC-mesenchymal stem cells and macrophages when co-cultured on hydroxyapatite-coated poly(lactic-co-glycolic acid)/poly(L-lactic acid) (HA-PLGA/PLLA) scaffolds. Both cell types seeded on the PLGA/PLLA especially with 5% w/v HA recapitulated the tissue remodeling process of human bone via coupling signals coordinating osteoblast and osteoclast activity and finely tuned expression of inflammatory molecules, resulting in accelerated in vitro bone formation. Following subcutaneous implantation in rodents, co-cultured hiPSC-MSC/-macrophage on such scaffolds showed mature bone-like tissue formation. These findings suggest the importance of coupling matrix remodeling through osteoblastic matrix deposition and osteoclastic tissue resorption and immunomodulation for tissue development.

UR - http://www.scopus.com/inward/record.url?scp=84971324360&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84971324360&partnerID=8YFLogxK

U2 - 10.1038/srep26761

DO - 10.1038/srep26761

M3 - Article

C2 - 27225733

AN - SCOPUS:84971324360

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 26761

ER -