Intervertebral Disc Stem/Progenitor Cells: A Promising “Seed” for Intervertebral Disc Regeneration

Abstract

Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain (LBP), which has become more prevalent from 21 century, causing an enormous economic burden for society. However, in spite of remarkable improvements in the basic research of IVD degeneration (IVDD), the effects of clinical treatments of IVDD are still leaving much to be desired. Accumulating evidence has proposed the existence of endogenous stem/progenitor cells in the IVD that possess the ability of proliferation and differentiation. However, few studies have reported the biological properties and potential application of IVD progenitor cells in detail. Even so, these stem/progenitor cells have been consumed as a promising cell source for the regeneration of damaged IVD. In this review, we will first introduce IVD, describe its physiology and stem/progenitor cell niche, and characterize IVDSPCs between homeostasis and IVD degeneration. We will then summarize recent studies on endogenous IVDSPC-based IVD regeneration and exogenous cell-based therapy for IVDD. Finally, we will discuss the potential applications and future developments of IVDSPC-based repair of IVD degeneration.

Spheroid-Based Tissue Engineering Strategies for Regeneration of the Intervertebral Disc

“…The slow expansion rate and the loss of native phenotypic features during the expansion in the monolayer are also potential drawbacks [ 45 ]. Multipotent tissue-specific NP progenitor cells (NPPC) were recently identified and investigated for their enhanced regenerative capacity [ 46 , 47 , 48 ]. NPPCs are characterized by a spheroid colony forming (in contrast to fibroblastic colony forming) and positivity for the cell surface marker angiopoietin-1 receptor (Tie2) [ 46 , 47 ].…”

“…Multipotent tissue-specific NP progenitor cells (NPPC) were recently identified and investigated for their enhanced regenerative capacity [ 46 , 47 , 48 ]. NPPCs are characterized by a spheroid colony forming (in contrast to fibroblastic colony forming) and positivity for the cell surface marker angiopoietin-1 receptor (Tie2) [ 46 , 47 ]. However, it has been a challenge to implement NPPC in clinics due to their extremely low yield and the fact that their numbers decrease with age and degeneration [ 46 , 47 ], but not as drastically as notochordal cells—a unique sub-population with stem cell properties originating from embryonic notochord [ 33 ].…”

“…NPPCs are characterized by a spheroid colony forming (in contrast to fibroblastic colony forming) and positivity for the cell surface marker angiopoietin-1 receptor (Tie2) [ 46 , 47 ]. However, it has been a challenge to implement NPPC in clinics due to their extremely low yield and the fact that their numbers decrease with age and degeneration [ 46 , 47 ], but not as drastically as notochordal cells—a unique sub-population with stem cell properties originating from embryonic notochord [ 33 ]. The transition of notochordal cells into chondrocyte-like cells before adulthood, and the subsequent decrease in proteoglycan content, is believed to cause NP degeneration [ 49 ].…”

Regulating the fate of stem cells for regenerating the intervertebral disc degeneration

“…Trials with disc stem cells revealed remarkable advantages in homing and retention in the IVD niche, differentiation capability, and functional competency. However, limitations in harvesting, separation, and proliferation of disc stem cells and low potency hinder researchers from using them for therapy[ 125 ]. Studies to overcome IVD injury using disc derived stem cells showed their ability to replace affected tissue by producing disc-specific collagen type II and proteoglycan, and restoring disc hydration to physiological state[ 126 , 127 ].…”

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods

“…Regenerative strategies that have garnered much interest in recent years are focused on elucidating the native developmental processes of the IVD to apply early developmental signals for in vivo tissue regeneration by combining tissue engineering using biomimetic scaffolds, targeted drug delivery for endogenous cell activation and differentiation, and exogenous cell implantation ( Pirvu et al, 2014 ; Pirvu et al, 2015 ; Richardson et al, 2016 ; Bowles and Setton, 2017 ; Baumgartner et al, 2021 ; Du et al, 2021 ). Improved understanding of intervertebral disc formation may enable reproduction of important developmental signals in the degenerated or injured discs as a regenerative strategy.…”