Engineering Bone Tissue Substitutes from Human Induced Pluripotent Stem Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2013 May 9

PMID 23653480

Citations 104

Authors

Giuseppe Maria de Peppo

Ivan Marcos-Campos

David John Kahler

Dana Alsalman

Linshan Shang

Gordana Vunjak-Novakovic

Darja Marolt

Affiliations

Soon will be listed here.

Abstract

Congenital defects, trauma, and disease can compromise the integrity and functionality of the skeletal system to the extent requiring implantation of bone grafts. Engineering of viable bone substitutes that can be personalized to meet specific clinical needs represents a promising therapeutic alternative. The aim of our study was to evaluate the utility of human-induced pluripotent stem cells (hiPSCs) for bone tissue engineering. We first induced three hiPSC lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. We then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 wk. Molecular analysis confirmed that the maturation of bone substitutes in perfusion bioreactors results in global repression of cell proliferation and an increased expression of lineage-specific genes. These results pave the way for growing patient-specific bone substitutes for reconstructive treatments of the skeletal system and for constructing qualified experimental models of development and disease.

Citing Articles

Prolonged cultivation enhances the stimulatory activity of hiPSC mesenchymal progenitor-derived conditioned medium.

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: an open-source 3D printable perfusion bioreactor and numerical model-based design strategy for tissue engineering.

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Mesenchymal Stromal Cells: Heterogeneity and Therapeutical Applications.

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Engineering of extracellular matrix from human iPSC-mesenchymal progenitors to enhance osteogenic capacity of human bone marrow stromal cells independent of their age.

Hanetseder D, Levstek T, Teuschl-Woller A, Frank J, Schaedl B, Redl H Front Bioeng Biotechnol. 2023; 11:1214019.

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