Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model.
OBJECTIVE
Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration.


METHODS
A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically.


RESULTS
No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs.


CONCLUSIONS
These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.
The Ritchie Centre, Monash Institute of Medical Research, Monash University, Clayton, Victoria;
David
D
Oehme
Peter
P
Ghosh
Susan
S
Shimmon
Jiehua
J
Wu
Courtney
C
McDonald
John M
JM
Troupis
Tony
T
Goldschlager
Jeffrey V
JV
Rosenfeld
Graham
G
Jenkin
D000818:Animals; D004195:Disease Models, Animal; D017586:Diskectomy; D007403:Intervertebral Disc / Q000473:pathology* / Q000601:surgery*; D008159:Lumbar Vertebrae / Q000601:surgery*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D012038:Regeneration / Q000502:physiology*; D012756:Sheep
D010426:Pentosan Sulfuric Polyester
AF = anulus fibrosus; AF1 = anular half containing the microdiscectomy; AF2 = anular half contralateral to the microdiscectomy; CEP = cartilaginous endplate; DHI = disc height index; GuHCl = guanidine hydrochloride; MPC = mesenchymal progenitor cell; MSC = mesenchymal stem cell; NIL = no treatment; NP = nucleus pulposus; PG = proteoglycan; PPS = pentosan polysulfate; SCAF = scaffold; VB = vertebral body; lumbar disc degeneration; mesenchymal progenitor cell; microdiscectomy; pentosan polysulfate; sheep; stem cell