The Analgesic Efficacy of Intradiscal Injection of Bone Marrow Aspirate Concentrate and Culture-Expanded Bone Marrow Mesenchymal Stromal Cells in Discogenic Pain: A Systematic Review

Abstract

Pain originating from the intervertebral disc (discogenic pain) is a prevalent manifestation of low back pain and is often challenging to treat. Of recent interest, regenerative medicine options with injectable biologics have been trialed in discogenic pain and a wide variety of other painful musculoskeletal conditions. In particular, the role of bone marrow aspirate concentrate (BMAC) and culture-expanded bone marrow derived mesenchymal stromal cells (BM-MSCs) in treating discogenic pain remains unclear. The primary objective of this systematic review was to appraise the evidence of intradiscal injection with BMAC and culture-expanded BM-MSCs in alleviating pain intensity from discogenic pain. Secondary outcomes included changes in physical function after intradiscal injection, correlation between stromal cell count and pain intensity, and anatomical changes of the disc assessed by radiographic imaging after intradiscal injection. Overall, 16 studies consisting of 607 participants were included in qualitative synthesis without pooling. Our synthesis revealed that generally intradiscal autologous or allogeneic BMAC and culture-expanded BM-MSCs improved discogenic pain compared to baseline. Intradiscal injection was also associated with improvements in physical functioning and positive anatomical changes on spine magnetic resonance imaging (improved disc height, disc water content, Pfirrmann grading) although anatomical findings were inconsistent across studies. However, the overall GRADEscore for this study was very low due to heterogeneity and poor generalizability. There were no serious adverse events reported post intradiscal injection except for a case of discitis.

Perspective on Intradiscal Therapies for Lumbar Discogenic Pain: State of the Science, Knowledge Gaps, and Imperatives for Clinical Adoption

“…There have been a large number of pilot investigations of the clinical effectiveness of intradiscal cell-based therapies. 7,13 While the findings of most reports suggest a positive treatment effect, their applicability is highly restricted due to extremely low sample sizes (ie, <10 cases) often generated by a single investigator from a single center. These important limitations are further compounded by lack of standardization of the intervention and variable reporting of relevant outcomes such as pain severity and functional improvement.…”

“…Therapeutic candidates including mesenchymal stromal cells (MSCs), platelet-rich plasma (PRP), nucleus pulposus (NP) tissue, and related cell-based agents have been proposed and can be delivered minimally-invasively under fluoroscopic guidance via a needle-based approach. [7][8][9][10][11][12][13][14][15] Both autologous products and their allogeneic analogs have been studied for relief of discogenic pain. 14,15 The underlying mechanism of action can involve the differentiation of chondrogenic precursor cells into viable regenerated disc tissue as with the injection of MSCs or the direct implantation of native disc material as with allogeneic NP.…”

Updates on Pathophysiology of Discogenic Back Pain

“…MSC therapy is likely the best candidate as this allows for autologous transplantation and multiple cell-type differentiation. The intradiscal injection of MSC shows an improvement in discogenic pain and functionality via stimulating ECM regeneration, downregulating pro-inflammatory cytokine production, and providing analgesic effects, but its therapeutic effects may be limited [20,157,158]. Autologous bone marrow aspirate concentrates injected intradiscally produced improvement in chronic discogenic low back pain for at least one year [159].…”

Minimally Invasive Intradiscal Delivery of BM-MSCs via Fibrous Microscaffold Carriers

“…For that purpose, several cell types were selected, including NP-derived cells, chondrocyte-like cells, mesenchymal stromal cells (MSCs), and induced pluripotent stem cells . Delivering cells to the IVD reduced the extent of fibrosis, increased NP hydration, and enhanced extracellular matrix (ECM) synthesis. , However, only a small percentage of cells survive due to cell death during needle injection, cell leakage, and the harsh environment of IVD . For this reason, multiple attempts are made to form cell-biomaterial constructs that could show promise in NP regeneration.…”