A Systematic Review of the Safety and Efficacy of Mesenchymal Stem Cells for Disc Degeneration: Insights and Future Directions for Regenerative Therapeutics

Abstract

Intervertebral disc degeneration is associated with low-back pain. Mesenchymal stem cells (MSCs) have been used to ''regenerate'' the disc. The aim of this study was to perform a systematic review of comparative controlled studies that have assessed the safety and efficacy of using MSCs for disc regeneration. Literature databases were extensively searched. Trial design, subject-type, MSC sources, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was performed. Twenty-four animal studies were included with 20.8% of the studies reporting randomization of groups. Trials in humans fulfilling inclusion criteria were not noted. The studies represented 862 discs that were injected with MSCs and 1,603 discs as controls. All three types of MSCs (ie, bone marrow, synovial, and adipose tissues) showed successful inhibition of disc degeneration. Bone-marrow-derived MSCs demonstrated superior quality of repair compared with other non-MSC treatments. A 2.7% overall complication rate was noted, whereby complications were noted only in rabbits. Overall, evidence suggested that MSCs increased disc space height in the majority of animal models. This is the first systematic review to assess the safety and efficacy of MSCs for the treatment of disc degeneration. Short-term MSC transplantation is safe and effective; however, additional, larger, and higher-quality studies are needed to assess the long-term safety and efficacy. Inconsistencies in methodological design and outcome parameters prevent any robust conclusions. Human-based clinical trials are needed. Recommendations are further made to improve efficacy, reduce potential complications, and standardize techniques for future studies.

Advancing cell therapies for intervertebral disc regeneration from the lab to the clinic: Recommendations of the ORS spine section

“…Therapeutic cell types such as MSCs may exhibit different phenotypic characteristics as a function of donor, age, species and anatomical site, and these characteristics may be closely linked to regenerative potential . While the development phase may necessitate the use of non‐human cells that are accessible and compatible with in vitro and in vivo models, the results obtained with these cells may not accurately reflect the performance of human cells that will be used clinically.…”

The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs

“…bone morphogenetic protein, Link N) have been shown to promote cell proliferation and/or matrix formation in vitro and/or in vivo in animal models with experimentally induced IVD degeneration (Chujo et al, 2006;Huang et al, 2007;Kwon et al, 2013;Masuda et al, 2006;Mwale et al, 2011). In addition, cell-based treatments using mesenchymal stromal cells (MSCs), articular chondrocytes and chondrocyte-like cells (CLCs) derived from the NP (Gilbert et al, 2013;Henriksson et al, 2011;Yim et al, 2014) have been tested. To date, however, only a limited number of regenerative therapies have entered the clinical…”

The UTE Disc Sign on MRI

“…stem cells, growth factors) have been developed to help regenerate or halt degeneration of a disc. 46 Also, being able to identify adjacent discs susceptible to degeneration/disease following a fusion or arthroplasty procedure is imperative. However, the limitations of conventional MRI, being not able to properly identify the clinically relevant and problematic disc, is a challenge, which may lead to undesirable outcomes.…”

“…However, the limitations of conventional MRI, being not able to properly identify the clinically relevant and problematic disc, is a challenge, which may lead to undesirable outcomes. 46 Furthermore, previous methods to identify symptomatic discs (e.g. discography) have also fallen out of favor since such procedures may risk progressive disc degeneration 47 and future pain development.…”