Porcine Intervertebral Disc Repair Using Allogeneic Juvenile Articular Chondrocytes or Mesenchymal Stem Cells

Abstract

Tissue engineering strategies for intervertebral disc repair have focused on the use of autologous disc-derived chondrocytes. Difficulties with graft procurement, harvest site morbidity, and functionality, however, may limit the utility of this cell source. We used an in vivo porcine model to investigate allogeneic non-disc-derived chondrocytes and allogeneic mesenchymal stem cells (MSCs) for disc repair. After denucleation, lumbar discs were injected with either fibrin carrier alone, allogeneic juvenile chondrocytes (JCs), or allogeneic MSCs. Discs were harvested at 3, 6, and 12 months, and cell viability and functionality were assessed qualitatively and quantitatively. JC-treated discs demonstrated abundant cartilage formation at 3 months, and to a lesser extent at 6 and 12 months. For the carrier and MSC-treated groups, however, there was little evidence of proteoglycan matrix or residual notochordal/chondrocyte cells, but rather a type I/II collagen-enriched scar tissue. By contrast, JCs produced a type II collagen-rich matrix that was largely absent of type I collagen. Viable JCs were observed at all time points, whereas no evidence of viable MSCs was found. These data support the premise that committed chondrocytes are more appropriate for use in disc repair, as they are uniquely suited for survival in the ischemic disc microenvironment.

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

“…Multiple preclinical animal studies have demonstrated the efficacy of intradiscally injected mesenchymal stem cells (MSCs) to induce disc regeneration. 1,2,16,18,20,21,25,[31][32][33][34]38,39,49,53,56,60,[64][65][66]69,73,83,87,90 Allogeneic mesenchymal progenitor cells (MPCs) are the earliest uncommitted clonogenic population of bone marrow stromal cells and have also successfully repaired the extracellular matrix following their injection into degenerative ovine discs. 25 Moreover, when ovine MPCs combined with the chondrogenic agent pentosan polysulfate (PPS) were embedded in a gelatin sponge and placed in a biodegradable cage that was implanted into the interbody space of ovine cervical spines, the cage became filled with a predominately cartilaginous matrix.…”

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

“…Chondrocytes proved to be more effective in restoring disc height and matrix production than MSCs or cell free controls (Acosta et al, 2011).…”

“…Cloyd et al, 2007;Gruber et al, 2006;Gupta et al, 2014;Hunt and Grover, 2010;Lazebnik et al, 2011;Nerurkar et al, 2010;Tilwani et al, 2012;Zhang et al, 2012 Fibrin Human plasma Surgical sealant Used as a singular or hybrid scaffold for NP and AF in vitro and in vivo testing. Acosta et al, 2011;Ahmed et al, 2008;Colombini et al, 2014;Diederichs et al, 2012;Eyrich et al, 2007;Hegewald et al, 2010;Ho et al, 2010;Likhitpanichkul et al, 2014;Ma et al, 2012;Park et al, 2011b;Pirvu et al, 2015;Schek et al, 2011;Stern et al, 2000;Stern et al, 2004;Sung et al, 1999;…”

In vitro extracellular matrix accumulation of nasal and articular chondrocytes for intervertebral disc repair

“…Despite showing improvements in symptoms and functionality following lumbar discectomy for symptomatic disc herniation, concerns remain with the use of alternative non-disc chondrocytes or mesenchymal stem cells (MSCs) (Acosta et al, 2011). In the case of NuQu®, issues still remain with supply and demand reconciliation using cadaveric juvenile chondrocytes and potential immunogenic reactions and rejection (Adkisson et al, 2010) which have not been elucidated for the disc microenvironment.…”

“…Despite significant advancements in the development of commercial ventures such as ADCT and NuQu®, identification of an alternative cell source for robust regeneration is crucial to further advancement. While investigative trials continue for immunoselected adipose derived precursor cells (Mesoblast Ltd., Australia), additional growth factors (GFs) such as transforming growth factor-beta 3 (TGF-β3) to induce and maintain chondrogenic differentiation (Acosta et al, 2011;Bobick et al, 2009) makes the use of adult MSCs challenging. Interestingly, within the degenerated human IVD, local progenitor cell populations have been identified previously (Risbud et al, 2007) and shown to exhibit slow cell proliferation kinetics in both annulus fibrosis and nucleus pulposus (Henriksson et al, 2009a) tissues.…”