Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

2-1-2016

Publication Source

Tissue Engineering - Part A.

Volume

22

Issue

3-4

Start Page

272

Last Page

285

DOI

10.1089/ten.tea.2015.0250

Abstract

Osteoarthritis is the leading cause of disability in the US. Consequently, there is a pressing need for restoring the structural and functional properties of diseased articular cartilage. Yet the search for the right combination of proper target cells and growth factors for cartilage regeneration remains challenging. In this study, we first tested the intrinsic chondrogenic differentiation ability of human perivascular stem cells (hPSCs), a novel source of mesenchymal stem cells (MSCs) isolated by fluorescence-activated cell sorting (FACS) from human adipose tissue. A putative prochondrogenic growth factor, NEL-like molecule-1 (NELL-1), was added to the hPSC pellets to upregulate gene expression of chondrogenic markers, including AGGRECAN, COLLAGEN II, and COMP. Furthermore, the addition of NELL-1 to a transforming growth factor beta 3 (TGF-β3) + bone morphogenetic protein-6 (BMP-6) "cocktail" resulted in the best combinatorial stimulation in accelerating the chondrogenic differentiation of hPSCs, as evidenced by increased gene and protein expression of chondrogenic markers in a shortened induction time without elevating expression of hypertrophic, fibrotic, and osteogenic markers. Mechanistically, this acceleration rendered by NELL-1 may be partially attributed to NELL-1's upregulation of BMP receptors and TGF-β receptor type I in hPSCs for increased responsiveness to BMPs + TGF-βs. In conclusion, lipoaspirate-derived hPSCs present a novel and abundant cell source of MSCs for cartilage regeneration, and the combinatorial application of NELL-1, TGF-β3, and BMP-6 with hPSCs may remarkably enhance and accelerate cartilage repair. © Copyright 2016, Mary Ann Liebert, Inc. 2016.

Comments

At the time of publication, author Chenshuang Li was affiliated with the Peking University, School and Hospital of Stomatology and the School of Dentistry, University of California. Currently, (s)he is a faculty member at the School of Medical Dentistry at the University of Pennsylvania.

Keywords

Antigens, Differentiation, Cell Culture Techniques, Cell Differentiation, Cells, Cultured, Chondrogenesis, Humans, Nerve Tissue Proteins, Stem Cells, Cartilage, Cells, Cytology, Flow cytometry, Flowcharting, Gene expression, Genes, Proteins, Stem cells, aggrecan, bone morphogenetic protein 2, bone morphogenetic protein 4, bone morphogenetic protein 6, bone morphogenetic protein receptor 1A, bone morphogenetic protein receptor 1B, bone morphogenetic protein receptor 2, cartilage oligomeric matrix protein, caspase 3, collagen type 10, collagen type 2, collagenase 3, cycline, glycosaminoglycan, growth factor, Ki 67 antigen, NEL like molecule 1, osteocalcin, osteopontin, transforming growth factor beta1, transforming growth factor beta3, unclassified drug, vasculotropin A, differentiation antigen, NELL1 protein, human, nerve protein, Bone morphogenetic proteins, Cartilage regeneration, Chondrogenic differentiation, Chondrogenic markers, Fluorescence activated cell sorting, Functional properties, Mesenchymal stem cell, Transforming growth factor beta, adipose tissue, Article, articular cartilage, cartilage cell, cell differentiation, cell isolation, chondrogenesis, fluorescence activated cell sorting, gene expression, human, human cell, human tissue, mesenchymal stem cell, perivascular stem cell, priority journal, protein expression, upregulation, biosynthesis, cell culture, cell culture technique, cell differentiation, chondrogenesis, cytology, drug effects, metabolism, procedures, stem cell, Cell culture

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Date Posted: 10 February 2023

This document has been peer reviewed.