Biologic Treatment of Mild and Moderate Intervertebral Disc Degeneration

Abstract

Disc degeneration is the most common cause of back pain in adults and has enormous socioeconomic implications. Conservative management is ineffective in most cases, and results of surgical treatment have not yet reached desirable standards. Biologic treatment options are an alternative to the above conventional management and have become very attractive in recent years. The present review highlights the currently available biologic treatment options in mild and moderate disc degeneration, where a potential for regeneration still exists. Biologic treatment options include protein-based and cell-based therapies. Proteinbased therapies involve administration of biologic factors into the intervertebral disc to enhance matrix synthesis, delay degeneration or impede inflammation. These factors can be delivered by an intradiscal injection, alone or in combination with cells or tissue scaffolds and by gene therapy. Cell-based therapies comprise treatment strategies that aim to either replace necrotic or apoptotic cells, or minimize cell death. Cell-based therapies are more appropriate in moderate stages of degenerated disc disease, when cell population is diminished; therefore, the effect of administration of growth factors would be insufficient. Although clinical application of biologic treatments is far from being an everyday practice, the existing studies demonstrate promising results that will allow the future design of more sophisticated methods of biologic intervention to treat intervertebral disc degeneration.

Autophagy: A double-edged sword in intervertebral disk degeneration

“…However, these interventions are limited to symptom management rather than therapy of underlying causes. Recently, biological treatments capable of preventing disc degeneration by promoting ECM repair and regeneration have been introduced and developed, including gene therapy [10,11], tissue engineering based on stem cells [12,13], administration of biologic factors into the degenerative IVD [14], and microRNA (miRNA) therapy [15,16]. With continued efforts, these novel methods may provide an alternative to surgical interventions for early stage disc degeneration Autophagy, literally meaning "self-eating" in Greek and discovered more than half a century ago, is an evolutionarily conserved process from yeast, plants, worms and flies to mammals.…”

“…ACCEPTED MANUSCRIPT 14 evidence that in both in vitro and in vivo model systems, TGF-β1 protects the IVDs from degeneration by inhibiting inflammatory responses [132], promoting ECM synthesis [133,134], and counteracting apoptosis of IVD cells [135]. Meanwhile, the effects of TGF-β1 on the cross-talk between apoptosis and autophagy in various types of cells has also been investigated with contradictory results.…”

Intra-discal injection of autologous, hypoxic cultured bone marrow-derived mesenchymal stem cells in five patients with chronic lower back pain: a long-term safety and feasibility study

“…Currently, there is no clinical therapy targeting the reversal of disc degeneration or that addresses intervertebral disc cell homeostasis [11, 12]. The regenerative medicine field using cell-based therapies and biologics has advanced significantly over the past decade with numerous clinical trials aiming at providing treatments for neurodegenerative, orthopedic and cardiovascular disorders [11, 13–15]. Mesenchymal stem cells (MSCs) are stem cells that have extensive proliferative capacity and multi-lineage potential.…”

Biologic Treatments in Intervertebral Disc Degeneration: Protein-Based and Cell-Based Therapies

“…To accomplish this task, many strategies have been examined. Intradiscal injection of specific anti-catabolic proteins (TIMPs) and pro-anabolic proteins including bone morphogenic proteins (BMP-2, -7, -12) 35 , growth and differentiation factor 5 (GDF-5) 36 , transforming growth factor beta(TGF-β) 37 , epidermal growth factor (EGF) 38 , insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) 39 have been evaluated 40 . Several drugs aimed at combating inflammatory cytokines have been investigated as well, including TNF-α antagonists and IL-1 receptor antagonists 41,42 .…”