Controversies in regenerative medicine: Should intervertebral disc degeneration be treated with mesenchymal stem cells?

Abstract

Low back pain (LBP) can significantly reduce the quality of life of patients, and has a considerable economic and social impact worldwide. It is commonly associated with disc degeneration, even though many people with degenerate discs are asymptomatic. Degenerate disc disease (DDD), is thus a common term for intervertebral disc (IVD) degeneration associated with LBP. Degeneration is thought to lead to LBP because of nerve ingrowth into the degenerate disc, inflammation, or because degradation of extracellular matrix (ECM) alters spinal biomechanics inappropriately. Thus, while the objectives of some interventions for LBP are to control pain intensity, other interventions aim to deal with the consequences of disc degeneration through stabilizing the disc surgically, by inserting artificial discs or by repairing the disc biologically and preventing progressive IVD degeneration. Despite tremendous research efforts, treatment of LBP through the use of regenerative interventions aiming to repair the IVD is still controversial. The use of mesenchymal stem cells for IVD regeneration in a patient‐based case will be discussed by an ensemble of clinicians and researchers.

Wnt3a and wnt5a as Potential Chondrogenic Stimulators for Nucleus Pulposus Cell Induction: A Comprehensive Review

“…Moreover, it remains undetermined whether the primary effect of transplanted cells is their immunomodulatory effects, endemic cell reactivation, active contribution to matrix production, or a combination thereof. [91][92][93] Nonetheless, MSCs are being explored in clinical setting, and their primary data suggest MSC transplantation to be safe and able to provoke clinical improvements. 7 In order to enhance the potency of MSCs to succeed in the IVD, multiple studies have explored the potential of preconditioning cells prior to IVD transplantation.…”

Therapeutic Potential of Extracellular Vesicles in Degenerative Diseases of the Intervertebral Disc

“…While current treatment options for DDD, including oral analgesics and surgery, solely aim to reduce the symptoms, researchers have made extensive efforts over the past decade to develop novel therapeutic approaches that target the underlying pathophysiological mechanisms, i.e., degeneration, inflammation, and enhanced apoptosis (Fernandez-Moure et al, 2018;Tendulkar et al, 2019). A wide range of approaches has been tested which are described in detail elsewhere (Krupkova et al, 2018;Smith et al, 2018;Clouet et al, 2019;Hodgkinson et al, 2019;Loibl et al, 2019), ranging from autologous disc cell therapy, growth factors, biologics, gene transfection, and biomaterials to CRISPR/Cas9 genome engineering, as well as the use of mesenchymal stem cells (MSCs). However, none of these concepts have been successfully incorporated yet into daily clinical practice.…”

“…As in numerous other fields, great hopes were pinned on MSCs for the treatment of DDD due to their regenerative and anti-inflammatory potential that would allow simultaneously targeting all primary pathological drivers (Vadala et al, 2016;Loibl et al, 2019). Furthermore, MSCs have excellent proliferation characteristics and good accessibility from either bone marrow or fat tissue.…”

The cartilage matrisome in adolescent idiopathic scoliosis

“…Approaches to IVD-targeted therapy could perhaps build upon the data armamentarium developed by the intervertebral disc degeneration (IVDD) research community, as well as on other successful gene therapy efforts. [106][107][108][109] Therapies proposed to stimulate ECM production in IVDD include local delivery of growth factors or viral-based gene therapy, or adoptive transfer of adult mesenchymal stem cells. In this regard, the avascular nature of the IVD and its limited systemic connection could prove advantageous for direct in vivo therapeutic delivery, similar to the eye.…”