Should Degenerated Intervertebral Discs of Patients with Modic Type 1 Changes Be Treated with Mesenchymal Stem Cells?

Abstract

Low back pain (LBP) has been among the leading causes of disability for the past 30 years. This highlights the need for improvement in LBP management. Many clinical trials focus on developing treatments against degenerative disc disease (DDD). The multifactorial etiology of DDD and associated risk factors lead to a heterogeneous patient population. It comes as no surprise that the outcomes of clinical trials on intradiscal mesenchymal stem cell (MSC) injections for patients with DDD are inconsistent. Intradiscal MSC injections have demonstrated substantial pain relief and significant disability-related improvements, yet they have failed to regenerate the intervertebral disc (IVD). Increasing evidence suggests that the positive outcomes in clinical trials might be attributed to the immunomodulatory potential of MSCs rather than to their regenerative properties. Therefore, patient stratification for inflammatory DDD phenotypes may (i) better serve the mechanisms of action of MSCs and (ii) increase the treatment effect. Modic type 1 changes—pathologic inflammatory, fibrotic changes in the vertebral bone marrow—are frequently observed adjacent to degenerated IVDs in chronic LBP patients and represent a clinically distinct subpopulation of patients with DDD. This review discusses whether degenerated IVDs of patients with Modic type 1 changes should be treated with an intradiscal MSC injection.

Postoperative Sclerotic Modic Changes after Transforaminal Lumbar Interbody Fusion

“…Inflammatory factors such as IL-8 and TNF-α play significant roles in the pathogenesis of preoperative MCs. 19,34 Second, early postoperative fusion may not occur at the vertebrae-cage interface, resulting in cage micromovement with the motion of the lumbar spine. In addition, patients with potential factors that affect fusion, such as high BMI, 35 smoking, 16 and osteoporosis, may experience in delayed bone fusion, leading to continued micromovements around the cage and subsequent postoperative sclerotic MCs.…”

Recent Advances in Managing Spinal Intervertebral Discs Degeneration

“…Moreover, MSC treatments are considered safe and well-tolerated, potentially limiting the inflammatory environment of the IVD upon transplantation and leading to no severe adverse effects. However, occasional mild-pain-related adverse events might occur [ 2 , 19 ].…”

“…Spinal disorders cover many pathologies (e.g., osteoporotic fractures, disc degeneration, spondylolisthesis, tumors, and large deformations), being among the most prevalent and costly medical conditions in Western societies [ 1 ]. Particularly, the degeneration of intervertebral discs (IVDs) has been considered the major cause of low back pain [ 2 , 3 , 4 , 5 ]. Mostly correlated with age, but not exclusively, IVD degeneration (IDD) can further aggravate into connected diseases, such as disc herniation, spinal canal stenosis, and spinal deformities [ 3 , 6 , 7 ].…”

Concepts of Regeneration for Spinal Diseases in 2022

“…In the papers reviewing current strategies for intervertebral disc regeneration, Herger N et al [ 7 ] hypothesized that pain relief and disability-related improvements by intradiscal mesenchymal stem cell (MSC) injection would result from the immunomodulatory potential rather than the regenerative properties. Hence, the application of intradiscal MSC injection to degenerative discs of patients with Modic type 1 pathologic inflammatory, fibrotic changes in the vertebral bone marrow was extensively reviewed.…”