Stem Cell Therapies for Degenerative Disc Disease

ORLANDO — Mesenchymal stem cell (MSC) therapy, also known as regenerative medicine therapy, is emerging as a promising treatment for degenerative disc disease (DDD). Wenchun Qu, MD, PhD, from Mayo Clinic in Rochester, Minnesota, reviewed the pathophysiology of DDD and advances in MSC preparation techniques at the American Academy of Pain Medicine 33^rd Annual Meeting in Orlando, Florida.¹

“Regenerative medicine therapy, contrary to what people would have believed a few years ago, is mainstream. It is not a futuristic hypothesis anymore. It is used in practice today, as evidence is accumulating and the next generation of engineered cells are emerging,” Dr Qu told Clinical Pain Advisor.

The pathogenesis of DDD involves a cycle of extracellular matrix breakdown, biomechanical factors (ie, microtrauma or increased mechanical load), and cell death (alters cytokine profile).^1,2 Factors that contribute to this cycle include increased body weight and processes that promote cell death, such as aging, genetics, and smoking.^1,2

Increases in proinflammatory cytokines stimulate matrix degrading enzymes and inhibit matrix synthesis, leading to dehydration of the nucleus pulposus and loss of disc height.¹ Pericytes, which comprise the endothelial lining of blood vessels, give rise to MSCs that exert an anti-inflammatory and immunomodulatory effect in response to injury.³ MSC therapy offers pain relief for patients with DDD and may slow the degenerative process of this condition.²

According to Dr Qu, the safety and efficacy of regenerative therapy for DDD is supported by 6 published studies, which showed that intradisc injections provided pain relief and functional improvement. “However, these results should be taken with a grain of salt because they are not large-scale randomized studies,” he cautioned.

Dr Qu outlined a 5-generation classification system for strategies for MSC preparation. First-generation strategies involve bone marrow aspiration of MSCs, which undergoes minimal manipulation (ie, centrifugation) prior to injection. Second-generation techniques culture the MSCs from bone marrow aspirate concentrate, and these culture-expanded MSCs have demonstrated efficacy for treating lumbar back pain and knee osteoarthritis.

MSCs can also be induced to differentiate into a specific cell line or undergo preconditioning to boost their effects in vivo (third generation). MSCs derived from bone marrow have been successfully differentiated into cardiopoietic cells and used in treatment of heart failure.

Fourth- and fifth-generation techniques use genetically modified MSCs and induced pluripotent stem cells (iPSCs), respectively; these have not been studied in clinical trials, and no clinical grade iPSCs have been developed. Further investigation is required to determine if these strategies are safe and effective for treating DDD.¹

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References

1. Qu W. Advance in stem cell preparation strategies. Presented at: the American Academy of Pain Medicine 33^rd Annual Meeting; March 16-19, 2017; Orlando, Florida.
2. Vergroesen PP, Kingma I, Emanuel KS, et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis Cartilage. 2015;23(7):1057-1070. doi: 10.1016/j.joca.2015.03.028
3. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45:e54. doi: 10.1038/emm.2013.94