Experimental Intervertebral Disc Regeneration with Tissue-Engineered Composite in a Canine Model

Abstract

The aims of this study were to construct the composite of poly (L-lactic-co-glycolic acid) (PLGA) scaffold-nucleus pulposus (NP) cells using tissue engineering methods and to investigate the in vivo performance of the composite in a canine model. NP cells were isolated from the lumbar intervertebral discs of a beagle dog. NP cells were cultured, expanded in vitro, and seeded onto a three-dimensional porous PLGA scaffold. The composite was tested in 18 beagle dogs that were randomly divided into three groups: nucleotomy alone (A), nucleotomy with PLGA implantation (B), and nucleotomy with PLGA scaffold/NP cells composite implantation (C). X-ray and magnetic resonance imaging were performed pre- and postoperatively. Evaluation of disc height, segment stability, and biomechanics and immunohistochemical analysis were performed. Dog NP cells attached and showed proliferation activity within the PLGA scaffold in vitro and in vivo. Disc height, segmental stability, and T2-weighted signal intensity on magnetic resonance imaging scans were well preserved in group C dogs with the engineered composite. PHK-26-positive cells were found within the area of the NP 8 weeks postoperatively. The NP cell-PLGA scaffold composite can prevent or delay the degeneration process after nucleotomy in the canine model. This hybrid composite might be a promising construct for intervertebral disc regeneration.

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

“…1,2,10,16,20,22,25,[30][31][32][34][35][36][37][38]46,48,49,53,54,56,57,60,62,[64][65][66][67]69,73,83,90 The EuroDISC study, by Meisel and colleagues, 49 investigated the percutaneous transplantation of autologous disc chondrocytes. Following microdiscectomy, disc chondrocytes were harvested and expanded in vitro and were subsequently injected into the NP 3 months postoperatively.…”

Efficacy of intradiscal hepatocyte growth factor injection for the treatment of intervertebral disc degeneration

“…The increase in type I collagen levels along with the corresponding decrease in type II collagen and PG levels in the disc matrix has been identified as a factor that causes the poor nutritional environment and inferior mechanical properties of degenerated discs (19). In samples of human lumbar intervertebral discs, type II collagen levels were demonstrated to be present at normal levels in the NP and in the inner layer of the AF; however, the A B levels were reduced in advanced degenerative discs.…”

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

“…Preclinical and clinical studies have used mesenchymal stem cells (MSCs) and the chondrocyte-like cells derived from the nucleus pulposus (NP) of the disc or juvenile articular cartilage to repair the intervertebral disc. 1,2,7,[13][14][15][22][23][24][25][26][27][28][29][30]38,39,57,59,74,75 Unlike disc chondrocytes, MSCs can be readily isolated from a variety of tissues including bone marrow, adipose tissue, and synovium. 9,76 Moreover, MSCs possess the capacity for self-renewal and thus maintain their undifferentiated phenotype in multiple subcultures, but when they are exposed to the appropriate stimuli, they can undergo differentiation into cells of the mesenchymal lineage, such as chondrocytes, osteocytes, and adipose cells.…”