Induction of Intervertebral Disc–Like Cells From Adult Mesenchymal Stem Cells

Abstract

The potential of adult mesenchymal stem cells (MSCs) to differentiate towards cartilage, bone, adipose tissue, or muscle is well established. However, the capacity of MSCs to differentiate towards intervertebral disc (IVD)-like cells is unknown. The aim of this study was to compare the molecular phenotype of human IVD cells and articular chondrocytes and to analyze whether mesenchymal stem cells can differentiate towards both cell types after transforming growth factor β (TGFβ)-mediated induction in vitro.Bone marrow-derived MSCs were differentiated in spheroid culture towards the chondrogenic lineage in the presence of TGFβ 3 , dexamethasone, and ascorbate. A customized cDNA-array comprising 45 cartilage-, bone-, and stem cell-relevant genes was used to quantify gene expression profiles.After TGFβ-mediated differentiation, MSC spheroids turned positive for collagen type II protein and expressed a large panel of genes characteristic for chondrocytes, including aggrecan, decorin, fibromodulin, and cartilage oligomeric matrix protein, although at levels closer to IVD tissue than to hyaline articular cartilage. Like IVD tissue, the spheroids were strongly positive for collagen type I and osteopontin. MSC spheroids expressed more differentiation markers at higher levels than culture-expanded IVD cells and chondrocytes, which both dedifferentiated in monolayer culture.In conclusion, mesenchymal stem cells adopted a gene expression profile that resembled native IVD tissue more closely than native joint cartilage. Thus, these cells may represent an attractive source from which to obtain IVD-like cells, whereas modification of culture conditions is required to approach the molecular phenotype of chondrocytes in hyaline cartilage. 2005;23:403-411 Stem Cells

Regeneration of intervertebral disc by mesenchymal stem cells: potentials, limitations, and future direction

“…Thus the potential of allogenic stem cells is worthy of further investigations using longer time points and larger animal models. [75]. Microarray analyses of the gene expression profiles were more consistent with annulus fibrosus cells of the IVD than a chondrocyte profile [75].…”

“…[75]. Microarray analyses of the gene expression profiles were more consistent with annulus fibrosus cells of the IVD than a chondrocyte profile [75].…”

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

“…These cells require cell-to-cell contact on three-dimensional spheres and growth factors such as TGF-b1 for development into NP-like cells [73,88]. After differentiation, these cells can be placed on a gel scaffold or directly injected into the disc [73,88].…”

“…These cells require cell-to-cell contact on three-dimensional spheres and growth factors such as TGF-b1 for development into NP-like cells [73,88]. After differentiation, these cells can be placed on a gel scaffold or directly injected into the disc [73,88]. Use of bone marrowderived mesenchymal stem cells has demonstrated the ability to slow degeneration by preserving disc health as evaluated by MRI, histology, immunohistochemistry, and gene expression [44,[78][79][80].…”

Is a collagen scaffold for a tissue engineered nucleus replacement capable of restoring disc height and stability in an animal model?

“…He showed that the cells proliferate but more proteoglycan was released into the culture medium and did not stay in the implant. Even stem cells could be a source of cells for tissue engineering, as they may differentiate into cells with an IVD-like phenotype as proven with a DNA copy of the mRNA (cDNA) [22].…”