Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model.
OBJECTIVE
There is an unmet need for a procedure that could generate a biological disc substitute while at the same time preserving the normal surgical practice of achieving anterior cervical decompression. The objective of the present study was to test the hypothesis that adult allogeneic mesenchymal progenitor cells (MPCs) formulated with a chondrogenic agent could synthesize a cartilaginous matrix when implanted into a biodegradable carrier and cage, and over time, might serve as a dynamic interbody spacer following anterior cervical discectomy (ACD).


METHODS
Eighteen ewes were divided randomly into 3 groups of 6 animals. Each animal was subjected to C3-4 and C4-5 ACD followed by implantation of bioresorbable interbody cages and graft containment plates. The cage was packed with 1 of 3 implants. In Group A, the implant was Gelfoam sponge only. In Group B, the implant consisted of Gelfoam sponge with 1 million MPCs only. In Group C, the implant was Gelfoam sponge with 1 million MPCs formulated with the chondrogenic agent pentosan polysulfate (PPS). In each animal the cartilaginous endplates were retained intact at 1 level, and perforated in a standardized manner at the other level. Allogeneic ovine MPCs were derived from a single batch of immunoselected and culture-expanded MPCs isolated from bone marrow of outbred sheep (mixed stock). Radiological and histological measures were used to assess cartilage formation and the presence or absence of new bone formation.


RESULTS
The MPCs with or without PPS were safe and well-tolerated in the ovine cervical spine. There was no significant difference between groups in the radiographic or histological outcome measures, regardless of whether endplates were perforated or retained intact. According to CT scans obtained at 3 months after the operation, new bone formation within the interbody space was observed in the Gelfoam only group (Group A) in 9 (75%) of 12 interbody spaces, and 11 (92%) of 12 animals in the MPC cohort (Group B) had new bone formation within the interbody space. Significantly, in the MPC & PPS group (Group C), there were only 1 (8%) of 12 levels with new bone formation (p = 0.0009 vs Group A; p = 0.0001 vs Group B). According to histological results, there was significantly more cartilaginous tissue within the interbody cages of Group C (MPC & PPS) compared with both the control group (Group A; p = 0.003) and the MPC Group (p = 0.017).


CONCLUSIONS
This study demonstrated the feasibility of using MPCs in combination with PPS to produce cartilaginous tissue to replace the intervertebral disc following ACD. This biological approach may offer a means preserving spinal motion and offers an alternative to fusion to artificial prostheses.
Goldschlager
Tony
T
Monash Immunology and Stem Cell Laboratories, Monash University, Clayton, Victoria, Australia.
Ghosh
Peter
P
Zannettino
Andrew
A
Gronthos
Stan
S
Rosenfeld
Jeffrey V
JV
Itescu
Silviu
S
Jenkin
Graham
G
D020341:Absorbable Implants / Q000706:statistics & numerical data*; D000818:Animals; D001705:Bioprosthesis; D002574:Cervical Vertebrae / Q000601:surgery*; D020219:Chondrogenesis / Q000187:drug effects* / Q000502:physiology; D015194:Diffusion Chambers, Culture; D017586:Diskectomy / Q000379:methods; D005240:Feasibility Studies; D005781:Gelatin Sponge, Absorbable; D007403:Intervertebral Disc / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D023421:Models, Animal; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology*; D012756:Sheep; D015503:Surgical Sponges; D023822:Tissue Engineering / Q000379:methods*
D010426:Pentosan Sulfuric Polyester