Review Article

Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

Table 1

Studies assessing the ability of disc derived and non-disc derived chondrocytes to regenerate lumbar intervertebral discs.

AuthorAnimal modelDegeneration modelCells transplantedMethod of cell administrationResults/conclusions

Bertram et al. [25]RabbitNucleotomy and axial compression
Amount of nucleus removed
Autologous NPCsPercutaneous injection in fibrin gel(i) 90% of cells leak out of disc space when injected in aqueous form
(ii) Injection within fibrin-thrombin gel decreased leakage to 50%
(iii) Intradiscal pressure limited cell survival

Ganey et al. [26]CanineNucleotomyAutologous disc chondrocytesIntradiscal injection(i) Transplanted cells remained viable and produced matrix similar in composition to native disc, including PGs
(ii) Increased types II and I collagen
(iii) Disc height maintained in cell treated group

Gorenšek et al. [27]RabbitNucleotomyAutologous auricular cartilage derived chondrocytesIntradiscal injection (i) Production of hyaline cartilage in the NP
(ii) Chondrocytes survived

Gruber et al. [28]RatPartial annulotomy and nucleotomy Autologous disc chondrocytesSurgical implantation(i) Transplanted cells remained viable producing matrix for up to 8 months
(ii) Cells in AF had fibroblast appearance cells in NP had chondrocyte appearance

Huang et al. [29]RabbitNucleotomyAllogeneic NPCsNPC-seeded collagenα/ hyaluronan/ chondroitin-6-sulfate tri-copolymer constructsNPC treated discs:
(i) Increased MRI T2 signal
(ii) Retard loss of disc height
(iii) Produced cartilaginous matrix within NP
(iv) Cells remained viable

Hohaus et al. [30]CanineAnnular injury and partial nucleotomyAutologous NPCs InjectionNP cells:
(i) Remain viable following implantation
(ii) PG and ECM cartilage produced
(iii) Types I and II collagen demonstrated
(iv) Maintain disc height

Iwashina et al. [31]RabbitPercutaneous aspiration of NPXenogeneic Human NPCsPercutaneous injectionNPC treated discs:
(i) Increased disc height
(ii) Significantly less degeneration using morphological and histological analysis
(iii) Increased proteoglycan synthesis
(iv) Increased expression of aggrecan, versican, and collagen II

Luk et al. [32]Rhesus monkeyTotal discectomyAllogeneic whole disc Allogeneic whole disc surgical transplantFresh disc allografts:
(i) Survive following transplantation
(ii) Undergo severe degeneration after 24 months

Meisel et al. [15]Canine DiscectomyAutologous disc derived chondrocytesIntradiscal injectionTransplanted cells:
(i) Remain viable
(ii) Produce matrix similar to normal disc
(iii) Type I and II collagens demonstrated in regenerated intervertebral disc
(iv) Maintained disc height

Nishimura and Mochida [33]RatPercutaneous nucleotomy Autologous NP tissuePercutaneous injection Implantation of NP tissue:
(i) Delayed degenerative changes
(ii) Preserved disc height

Nomura et al. [34]RabbitPercutaneous aspiration of NPAllogeneic NP cells and intact NP tissuePercutaneous injection (i) No immune or inflammatory response from allogeneic cell implantation
(ii) Implantation of intact nucleus and NP cells reduced degeneration
(iii) Increased type II collagen post implantation

Okuma et al. [35]RabbitPercutaneous NP aspirationAutologous NP cellsPercutaneous injection of NP cells cocultured with AF cellsCell treated discs:
(i) Delayed cell clustering
(ii) Rate of degeneration slowed histologically
(iii) Cells elaborated type II collagen

Ruan et al. [36]CanineNucleotomyAutologous NPCsNP cells seeded onto L-lactic-co-glycolic acid (PLGA) scaffold(i) Disc height, segmental stability, and MRI T2 signal preserved in NP treated discs
(ii) PKH-26 labelled cells found in NP at 8 weeks

Sato et al. [37]RabbitVaporized using laserAllogeneic annulus fibrosus cellsAnnulus fibrosus cells cultured in atelocollagen honeycomb-shaped scaffold and labelled with PKH-26 fluorescent dye Transplanted cells:
(i) Prevented loss of disc height
(ii) Remained viable at 12 weeks
(iii) Produced hyaline cartilage

AF: annulus fibrosis, ECM: extracellular matrix, NP: nucleus pulposus, NPCs: nucleus pulposus cells, and PGs: proteoglycans.