Discogenic cell transplantation directly from a cryopreserved state in an induced intervertebral disc degeneration canine model

Abstract

A multitude of studies has indicated the potential of cell therapy as a method for intervertebral disc (IVD) regeneration. Transplantation of a variety of cells has been assessed and shown capable of deterring the rate of degeneration in animal models and in human clinical trials. In this study, a novel approach using human discogenic nucleus pulposus cells directly from their cryopreserved state was assessed. In an established canine disc degeneration model, the degeneration process was evaluated in IVDs receiving precultured discogenic cells, thawedonly discogenic cells, and a saline sham injection after induction of degeneration. Degeneration progression was followed over time by the evaluation of the disc height index (DHI). Finally, after 12 weeks, the manipulated and control discs were explanted, histologically stained, and of the estimated 632 million low back pain patients globally will advance to a chronic condition. 1,2 Together, these compelling numbers engender a critical social-economic burden on society. For example, within the USA, 100 billion USD is spent annually on low back pain associated costs. 3,4 Currently, treatment options are limited and fail to restore or halt further advancement of the underlying pathology. 5 Degeneration of the intervertebral disc (IVD) is widely considered to be a predominant cause of low back pain. IVD degeneration is hallmarked by a dysregulation in extracellular matrix (ECM) homeostasis. 6,7 The exact origin of IVD degeneration remains to be elucidated; however, the nucleus pulposus (NP) is believed to be the place of onset. 8,9 Progression of IVD degeneration is characterized by a decline in proteoglycan production, an increase in matrix degenerative proteins, and a switch from type II collagen to type I collagen production. 6,7 Moreover, NP cells undergo senescence and dedifferentiation toward a more fibrotic phenotype. 10 The NP disorganization and height loss causes incorrect loading of adhering tendons promoting reorganization of tendon ECM to thicker and stiffer structures, further disrupting the mechanical features along the spine.

Annulus fibrosus cell sheets limit disc degeneration in a rat annulus fibrosus injury model

“…In the future, AF cell sheets might be applied in combination with NP cell therapy, [55][56][57] to further curtail or even reverse IVD degeneration. 10,58 Although our study provides evidence to the benefits of cell sheet technology for IVD repair, the study does have some limitations.…”

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

“…IDCT contains a mixture of specialized therapeutic progenitor cells engineered from donated adult disc tissue, or “discogenic” cells and a viscous carrier material. Promising animal data suggests a potential therapeutic benefit of IDCT, including disc height improvement and normalization of disc architecture, and a safe profile . Aesculap Biologics (Breinigsville, Pennsylvania) is currently testing NOVOCART DISC in a Phase II trial in the European Union.…”

“…Promising animal data suggests a potential therapeutic benefit of IDCT, including disc height improvement and normalization of disc architecture, and a safe profile. 31 Aesculap Biologics (Breinigsville, Pennsylvania) is currently testing NOVOCART DISC in a Phase II trial in the European Union. This treatment is a combination of autologous disc chondrocytes and a self-polymerizing hydrogel (clinicaltrials.gov study identifier NCT01640457) that is already being used clinically for articular cartilage repair in the knee.…”

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

“…7 Nevertheless, an optimal cell type or preconditioning method to enable optimized regeneration of NP tissue has not yet been established. [8][9][10] Wnt signaling holds a key role in joint development, homeostasis, and pathogenesis. The prominence of wnt signaling in cartilage tissues was initially discovered in chicken limb cartilage.…”