Cervical Interbody Fusion Is Enhanced by Allogeneic Mesenchymal Precursor Cells in an Ovine Model

Goldschlager, Tony; Rosenfeld, Jeffrey V.; Ghosh, Peter; Itescu, Silviu; Blecher, Carl M.; McLean, Catriona; Jenkin, Graham

doi:10.1097/brs.0b013e3181dfcec9

Cited by 47 publications

(36 citation statements)

References 51 publications

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“…17 On the basis of these results, and notwithstanding the absence of the osteoconductive hydroxyapatite/tricalcium phosphate granules, it might be predicted that a greater amount of new bone formation was deposited within the cage after 12 weeks than was observed by CT in the present study. While it is possible that with time these small bone spurs may advance to frank bone bridging, the radiographic and histological studies clearly showed that after 12 weeks there was an increased frequency of bone spur deposition in cages containing MPC alone compared with the formulation containing MPC & PPS.…”

Section: Discussioncontrasting

confidence: 41%

Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model

Goldschlager

Ghosh

Zannettino

et al. 2010

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Object 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.

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Section: Discussioncontrasting

confidence: 41%

Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model

Goldschlager

Ghosh

Zannettino

et al. 2010

FOC

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“…Seven studies (84 levels) reported imaging and/or histology outcomes for ACDF at 12 weeks postoperative using the following groups: autograft, empty titanium cages, titanium cages filled with autograft, and PEEK cages filled with autograft [23][24][25][26][27][28][29]. One of the studies of ACDF with autograft included fixation with an anterior plate [23].…”

Section: Acdfmentioning

confidence: 98%

An analysis of spine fusion outcomes in sheep pre-clinical models

et al. 2016

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Recommended timeframes for future studies designed to show either superiority over controls or equivalent outcomes with controls were developed based on aggregate results. Designating ideal study endpoints for sheep fusion models has both ethical implications associated with responsible use of animals in research, and economic implications given the cost of animal research. The current results can guide the development of future research methods and help investigators choose appropriate study timelines for various control groups.

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“…They are readily available and show great homogeneity when selected for age, breed and sex [8]. Moreover, the ovine IVD has been used as model of IDD [10,11] and as preclinical model to test biological therapies such as growth factor or stem cell treatments [12]. It has become more popular to test vertebral implants and fusion technologies [13] due to the similar size and volume of the vertebrae to humans, which allow the use of the same devices and instrumentation as under clinical conditions [8].…”

Section: Introductionmentioning

confidence: 99%

The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization

et al. 2013

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Purpose To characterize in vivo the transpedicular approach (TA) as an alternative route to study intervertebral disc (IVD) regeneration strategies in a sheep model. Methods 48 IVD of 12 sheep were used. TA was performed under fluoroscopy, followed by nucleotomy (2-mm shaver resector). A polyurethane scaffold was used to repair the end-plate. X-ray and MRI images were acquired pre-, intra-and post-operatively (1, 3, 6 months). Complications were recorded. Results TA was feasible in all animals; nucleus pulposus (NP) from L1 to L5 was accessible. Nucleotomy followed by end-plate repair was achieved. Loss of NP signal intensity was shown in MRI images of the nucleotomy group. Conclusions TA is feasible in vivo, repeatable after only a short learning period and safely performed without significant morbidity. This animal model allows the study of IVD degeneration physiopathology and investigation of IVD regeneration techniques in vivo.

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Cervical Interbody Fusion Is Enhanced by Allogeneic Mesenchymal Precursor Cells in an Ovine Model

Cited by 47 publications

References 51 publications

Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model

Cervical motion preservation using mesenchymal progenitor cells and pentosan polysulfate, a novel chondrogenic agent: preliminary study in an ovine model

An analysis of spine fusion outcomes in sheep pre-clinical models

The transpedicular approach for the study of intervertebral disc regeneration strategies: in vivo characterization

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