Accelerated Chondrogenic Differentiation of Human Perivascular Stem Cells with NELL-1
Penn collection
Degree type
Discipline
Subject
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
Dentistry
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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.