Injection of human umbilical tissue–derived cells into the nucleus pulposus alters the course of intervertebral disc degeneration in vivo

Abstract

Background context Patients often present to spine clinic with evidence of intervertebral disc degeneration (IDD). If conservative management fails, a safe and effective injection directly into the disc might be preferable to the risks and morbidity of surgery. Purpose To determine whether injecting human umbilical tissue–derived cells (hUTC) into the nucleus pulposus (NP) might improve the course of IDD. Design Prospective, randomized, blinded placebo–controlled in vivo study. Patient sample Skeletally mature New Zealand white rabbits. Outcome measures Degree of IDD based on magnetic resonance imaging (MRI), biomechanics, and histology. Methods Thirty skeletally mature New Zealand white rabbits were used in a previously validated rabbit annulotomy model for IDD. Discs L2–L3, L3–L4, and L4–L5 were surgically exposed and punctured to induce degeneration and then 3 weeks later the same discs were injected with hUTC with or without a hydrogel carrier. Serial MRIs obtained at 0, 3, 6, and 12 weeks were analyzed for evidence of degeneration qualitatively and quantitatively via NP area and MRI Index. The rabbits were sacrificed at 12 weeks and discs L4–L5 were analyzed histologically. The L3–L4 discs were fixed to a robotic arm and subjected to uniaxial compression, and viscoelastic displacement curves were generated. Results Qualitatively, the MRIs demonstrated no evidence of degeneration in the control group over the course of 12 weeks. The punctured group yielded MRIs with the evidence of disc height loss and darkening, suggestive of degeneration. The three treatment groups (cells alone, carrier alone, or cells+carrier) generated MRIs with less qualitative evidence of degeneration than the punctured group. MRI Index and area for the cell and the cell+carrier groups were significantly distinct from the punctured group at 12 weeks. The carrier group generated MRI data that fell between control and punctured values but failed to reach a statistically significant difference from the punctured values. There were no statistically significant MRI differences among the three treatment groups. The treated groups also demonstrated viscoelastic properties that were distinct from the control and punctured values, with the cell curve more similar to the punctured curve and the carrier curve and carrier+cells curve more similar to the control curve (although no creep differences achieved statistical significance). There was some histological evidence of improved cellularity and disc architecture in the treated discs compared with the punctured discs. Conclusions Treatment of degenerating rabbit intervertebral discs with hUTC in a hydrogel carrier solution might help restore the MRI, histological, and biomechanical properties toward those of nondegenerated controls. Treatment with cells in saline or a hydrogel carrier devoid of cells also might help restore some imaging, architectural, and physical properties to the degenerating disc. These data support the potential use of therapeutic cells in the treatment of dis...

Co-culture of human nucleus pulposus cells with multipotent mesenchymal stromal cells from human bone marrow reveals formation of tunnelling nanotubes

“…An alternative approach is the co-culture of IVD cells with MSCs in the 'one-surface system' (also known as direct co-culture or contact system), three-dimensional systems (alginate beads) and culture of two cell lines separated by a porous membrane (also termed insert system, indirect co-culture or non-contact system) (19). Injection of MSCs into the disc space was also assayed (16,20).…”

Comparison of biological characteristics of nucleus pulposus mesenchymal stem cells derived from non-degenerative and degenerative human nucleus pulposus

“…Numerous stem cell types have been used in the field of cell transplantation for the treatment of IDD, such as bone marrow-derived stem cells (BMSCs) (10), adipose-derived MSCs (ADMSCs) (11), human umbilical tissue-derived cells (12) and synovium-derived stem cells (13 (14,15). Certain studies have reported that these stem cells lack viability, proliferation and matrix biosynthesis under conditions resembling the IVD microenvironment, which negatively influences the biological and metabolic vitality of stem cells and impairs their repair potential (16,17).…”

A future in our past: the umbilical cord for orthopaedic tissue engineering

“…Some have observed that UC-MSCs, compared with BM-MSCs, are characterized by superior extracellular matrix synthesis in terms of glycosaminoglycans (GAGs) and collagen I production, consistent with a "fibrocartilaginous" commitment, while BM-MSCs seem to be more prone to collagen II synthesis and, consequently, to show better chondrogenic differentiation (15). For these reasons, UC-MSCs seem to be good candidates for intervertebral disk regeneration, as shown in different studies (16,17). Even though this preclinical application may provide an intriguing solution to a major problem in the general population, we, on the other hand, still believe that UC-MSCs offer potential for cartilage regeneration.…”