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

Abstract

Over the past few years, substantial progress has been made in the field of stem cell regeneration of the intervertebral disc. Autogenic mesenchymal stem cells in animal models can arrest intervertebral disc degeneration or even partially regenerate it and the effect is suggested to be dependent on the severity of degeneration. Mesenchymal stem cells (MSCs) are able to escape alloantigen recognition which is an advantage for allogenic transplantation. A number of injectable scaffolds have been described and various methods to pre-modulate MSCs' activity have been tested. In future, work will need to address the use of mesenchymal stem cells in large animal models and the fate of the implanted mesenchymal stem cells, particularly in the long term, in animals. This review examines the state-of-the-art in the field of stem cell regeneration of the intervertebral disc, and critically discusses, with scientific support, the issues involved, before stem cells could be used in human subjects. [79,81]. In the development of organism, the single totipotent cell after fertilization divides and specializes into pluripotent cells, such as embryonic stem cells that are necessary for fetal development. The pluripotent cells then further specialize into multipotent cells that commit into lineages with tissue-specific functions. Cells have been successfully identified in or isolated from embryonic [70], fetal [34, 73], or adult tissues [45] and demonstrated to have stem cell-like properties in vitro and in vivo. The maintenance, survival and activity of these stem cells is suggested to be dependent on the special micro-environmental niche [45], such that uncommitted pluripotent stem cells can be induced to differentiate to form a particular cell type by the nature of the environment. Additionally, the pluripotency of stem cells depends on the source, the method of isolation, and conditions of ex-vivo cell processing.

Dysregulated miR-98 Contributes to Extracellular Matrix Degradation by Targeting IL-6/STAT3 Signaling Pathway in Human Intervertebral Disc Degeneration

“…(27) Most intervertebral disc regeneration studies have mainly focused on repair of the NP. (28) Therefore, the experiments revolve around NP cells in our study.…”

Human mesenchymal stem cells implantation into the degenerated coccygeal disc of the rat

“…Therefore, research on MSCs has recently intensified (Jiang et al 2002). However, few studies on MSC-based treatments for IVD degeneration have been undertaken (Leung et al 2006;Preston et al 2003;Prockop 1997). In the present study, we explored the effects of human MSC implantation on the restoration of degenerative intervertebral discs (IVDs) in the rat.…”

“…The changes that occur in degenerative IVDs include decreases in chondrocytes, extracellular matrix components, proteoglycan, and Type II collagen, and increases in inflammatory substances and enzymes, such as, the metalloproteinases. Therefore, IVD degeneration is presumed to commence with a decline in the extracellular matrix of the nucleus pulposus, and to culminate in reduced matrix and water content in this tissue, which results in cracks or microfractures in the annulus fibrosus (Leung et al 2006). Consequently, dynamic imbalance reduces shock-absorbing capacity, which is required to attenuate the effects of external impacts or loads.…”

“…It has been reported that collagen and proteoglycan levels improve after gene therapy with transfected adenovirus strains expressing SOX9, TGF-b1, TIMP1, and BMP2 (Wallach et al 2003;Paul et al 2003;Nishida et al 1999), and that proteoglycan levels increase after injecting OP-1 (BMP-7), GDF-5, and LMP-1 directly into an IVD Kawakami et al 2005;Li et al 2002;Takegami et al 2005;Yoon et al 2004). However, this approach is unreliable because it does not directly increase the numbers of IVDs cells, and thus, is problematic as a potential therapy for degenerative IVD conditions (Leung et al 2006).…”

“…However, because the supply of autologous IVD cells is problematic (Okano 2002), the notion of using stem cells in this context has increased in importance, and trials are currently in progress (Crevensten et al 2004;Leung et al 2006;Sakai et al 2006Sakai et al , 2005Sakai et al , 2003.…”