Stem cell–mediated regeneration of the intervertebral disc: cellular and molecular challenges

Abstract

<jats:p>✓ Regenerative medicine and stem cells hold great promise for intervertebral disc (IVD) disease. The therapeutic implications of utilizing stem cells to repair degenerated discs and treat back pain are highly anticipated by both the clinical and scientific communities. Although the avascular environment of the IVD poses a challenge for stem cell–mediated regeneration, neuroprogenitor cells have been discovered within degenerated discs, allowing scientists to revisit the hostile environment of the IVD as a target for stem cell therapy. Issues now under investigation include the timing of cell delivery and manipulation of stem cells to make them more efficient and adaptive in the IVD niche. This review covers the mechanisms underlying disc degeneration as well as the molecular and cellular challenges involved in directing stem cells to the desired cell type for intradiscal transplantation.</jats:p>

Human Adipose-Derived Mesenchymal Stem Cells: Direction to a Phenotype Sharing Similarities with the Disc, Gene Expression Profiling, and Coculture with Human Annulus Cells

“…Although maintenance and regulation of proteoglycan synthesis is also critical within the nucleus pulposus, we have chosen annulus cells here because of our specific interest in development of clinically appropriate future biologic therapies for disc degeneration, especially those that might employ autologous disc and MSC or AD-MSC therapies. [27][28][29][30][31][32][33][34] We concur with An et al and others that for clinical applications, research on the annulus is a logical first step since no therapeutic methods for the nucleus would be likely to be successful in the environment of a compromised annulus tissue. 35,36 Ultimately, it is the ECM of the annulus that fails in disc degeneration; dehydration and matrix fraying culminate in the formation of tears within the …”

A Global Pictorial Assessment of the Intervertebral Disc Cell in Several Species Reveals a Remarkable Biodiversity in this Cell Type which should be taken into Account in Experimental Studies on Intervertebral Disc Repair

“…Oocytes are also surrounded by an extensive HA coat which is depolymerised post-fertilization this is a relatively poorly researched area of ECM remodeling however with scant details available on how this actually occurs. The human genome contains 6 hyaluronidase-like genes Hyal1, Hyal2, Hyal3, Hyal4, HyalP1 and PH20 [51]. HyalP1 is an inactive pseudogene and PH20 is a testicular enzyme.…”

Nucleus pulposus tissue engineering: a brief review

“…Chondrocytes and cells from the central regions of the disc normally produce these matrix proteins, making them candidates for cell-based disc repair. Moreover, development of stem cell research in the past decade provides an attractive prospect of adult MSCs for NP tissue engineering [23,25,27,44,49,50,54,56,61,64].The study of MSCs was initiated by Friedenstein and colleagues [15] more than 40 years ago. So far it has been well recognized that MSCs have the ability to differentiate along various lineages of mesenchymal origin, including chondrocyte, osteoblast, and adipocyte lineages, depending upon the biological environment, and can be obtained from multiple adult tissues such as bone marrow, trabecular bone, articular cartilage, muscle, and adipose [6].…”

“…Treatment of disc degeneration remains still a great challenge to both clinical physicians and basic researchers. As a biological treatment strategy, tissue engineering approach has received considerable attention during the last decade, and the achievements and challenges in this field have been well documented in several reviews [25,27,44,46].…”