Abstract
Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies.
Highlights
The intervertebral disc (IVD) arises from the embryonic notochord and mesenchyme and develops into a complex tissue that permits movement between vertebrae and provides flexibility and integrity to the spine [1]
Matrix repair is impaired in the avascular IVD, resulting in weakening and increased vulnerability to damage by physiologic loading
Interim analysis of 50% of the patients after 6 months follow-up indicated a greater reduction in low back pain and an improvement in function in patients receiving 6*106 immunoselected and culture-expanded Mesenchymal stromal cells (MSC) compared with control patients
Summary
The intervertebral disc (IVD) arises from the embryonic notochord and mesenchyme and develops into a complex tissue that permits movement between vertebrae and provides flexibility and integrity to the spine [1]. NCconditioned medium (NCCM; medium in which NCs or NC-containing tissue is cultured for 4 days and comprises NC-secreted soluble factors) has the potential to increase NP GAG production and cell proliferation [61,62,63] Both NCCM and CLC + NC coculture stimulate the in vitro differentiation of MSCs into a NP-like phenotype with a high chondrogenic matrix production [36,39,42,59,60,64,65]. The performed regenerative IVD studies show halting of degeneration (by increased disc height, proteoglycan or water content, and improved clinical status of patients during follow-up), but it is not known whether the cellbased IVD treatment strategies were able to regenerate NP tissue. Human and canine patients with IVD degeneration can be used as a study population to investigate the mechanisms of degeneration and potential regenerative treatments, which is beneficial for both species and suits the ‘One Health’ concept
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