In vitro and in vivo evaluation of discogenic cells, an investigational cell therapy for disc degeneration

Abstract

BACKGROUND/CONTEXT: Disc degeneration (DD) is a significant driver of low back pain and few treatments exist to treat the pain and disability associated with the disease. PURPOSE: Our group has developed a method to generate therapeutic discogenic cells as a potential treatment for symptomatic DD. These cells are derived and modified from adult nucleus pulposus cells. In this study, we evaluated the characteristics, mode of action, and in vivo efficacy and safety of these cells prior to human clinical testing. STUDY DESIGN: Privately funded in vitro studies and in vivo preclinical models were used in this study. METHODS: Discogenic cells generated from different adult human donors were evaluated for surface marker expression profile, matrix deposition and tumorigenic potential. Discogenic cells were then injected subcutaneously into nude mice to assess cell survival and possible extracellular matrix production in vivo. Finally, a rabbit model of DD was used to evaluate the therapeutic potential of discogenic cells after disc injury. RESULTS: We found that discogenic cells have a consistent surface marker profile, are multipotent for mesenchymal lineages, and produce extracellular matrix consisting of aggrecan, collagen 1 and collagen 2. Cells did not show abnormal karyotype after culturing and did not form tumor-like aggregates in soft agar. After subcutaneous implantation in a nude mouse model, the human discogenic cells were found to have generated regions rich with extracellular matrix over the course of 4 months, with no signs of tumorigenicity. Intradiscal injection of human discogenic cells in a rabbit model of DD caused an increase in disc height and improvement of tissue architecture relative to control discs or injection of vehicle alone (no cells) with no signs of toxicity. CONCLUSIONS: This study demonstrates that intradiscal injection of discogenic cells may be a viable treatment for human degenerative disc disease. The cells produce extracellular matrix that FDA device/drug status: Not applicable.

Improving Cell Therapy Survival and Anabolism in Harsh Musculoskeletal Disease Environments

“…109 There has also been a preclinical study using preconditioned cells from the NP of human IVD tissue, called discogenic cells, with promising outcomes. 110,111 These are cells extracted from NP tissue and expanded in a proprietary cocktail of supplements before insertion into degenerative IVD tissue. Preclinical studies demonstrated the ability of discogenic cells to significantly partially restore lost disc height and improve morphology compared with vehicle or sham controls while demonstrating these cells are safe too.…”

New Insights Into Immunological Therapy for Retinal Disorders

“…In a previous study, suppression of activated microglia/macrophages with minocycline or toxin-induced depletion of CX3CR1-positive microglia/macrophages protected rod cells against cell death in retinal degeneration (rd) 10 mice (135,136). However, attenuation of the homeostatic function of microglia by disrupting the CX3C chemokine ligand 1-CX3C chemokine receptor 1 axis or the complement component 3-complement receptor 3 axis accelerates rod degeneration, along with proinflammatory microenvironmental changes such as increased TNF-α and IL-6 levels (137,138). Therefore, microglia/macrophages have a bidirectional function in RP, as expected from the basic understanding of the interaction between cell death and inflammation.…”

Perspectives on the Treatment of Lumbar Disc Degeneration: The Value Proposition for a Cell-Based Therapy, Immunomodulatory Properties of Discogenic Cells and the Associated Clinical Evaluation Strategy

“…During the growth process, cells exhibit phenotypic changes from that of cells found in the native disc tissue. Specifically, the cells lose expression of CD24 (44), which is a marker for nucleus pulposus cells (45). Also, Discogenic Cells have a unique surface marker expression profile that includes high expression of CD73, CD90, and HLA-ABC and a low expression of CD34 and HLA-DR/DQ/DP (44).…”

“…Specifically, the cells lose expression of CD24 (44), which is a marker for nucleus pulposus cells (45). Also, Discogenic Cells have a unique surface marker expression profile that includes high expression of CD73, CD90, and HLA-ABC and a low expression of CD34 and HLA-DR/DQ/DP (44). The cells generate the extracellular matrix found within native intervertebral disc tissue, including proteoglycan and collagen.…”