Transplantation of mesenchymal stem cells in a canine disc degeneration model

Hiyama, Akihiko; Mochida, Joji; Iwashina, Toru; Omi, Hiroko; Watanabe, Takuya; Sakai, Kenji; Tamura, Futoshi; Sakai, Daisuke

doi:10.1002/jor.20584

Cited by 214 publications

(176 citation statements)

References 51 publications

(50 reference statements)

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“…Nevertheless there are now both animal and human studies into cell therapies for the disc, suggesting that this approach may be feasible. It has been shown that reinsertion of autologous nucleus pulposus cells or stem cells delays degeneration in experimental models of disc degeneration [32,39,65,80,98,108] and injection of autologous nucleus pulposus cells are being used in humans with herniated discs [65]. However, it is not yet clear what the optimal implant will be.…”

Section: Tissue Engineering and The Intervertebral Discmentioning

confidence: 99%

Tissue engineering and the intervertebral disc: the challenges

2008

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Disc degeneration is a common disorder. Although the back pain that can develop in association with this is rarely life-threatening, the annual cost in terms of morbidity, lost productivity, medical expenses and workers' compensation benefits is significant. Surgical intervention as practised currently is directed towards removing the damaged or altered tissue. Development of new treatment modalities is critical as there is a growing consensus that the strategies used currently for symptomatic degenerative disc disease may not be effective. Accordingly, there is a need to develop an entirely new way to treat this disorder; regenerative medicine and tissue engineering approaches appear particularly promising in this regard. This paper reviews some of the challenges that currently are limiting the clinical application of this approach to the treatment of disc degeneration.

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Section: Tissue Engineering and The Intervertebral Discmentioning

confidence: 99%

Tissue engineering and the intervertebral disc: the challenges

2008

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“…MSCs have also been widely used for treatment of osteoarthritis in dogs, a progressive degenerative condition that also has an associated inflammatory component. Studies of canine adiposederived MSC (Ad-MSC) and bone marrow-derived MSC (BM-MSC) injected into the elbow and hip joints of dogs with osteoarthritis produced positive results in terms of improvement in clinical measures of osteoarthritis reported in most investigations [44][45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

ChowLyndah

JohnsonValerie

CoyJonathan

et al. 2017

Stem Cells and Development

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Mesenchymal stem cells (MSCs) from rodents and humans have been shown to suppress T cells by distinct primary pathways, with nitric oxide (NO)-dependent pathways dominating in rodents and indoleamine 2,3-deoxygenase (IDO)-dependent pathways dominating in humans. However, the immune suppressive pathways utilized by canine MSC have not been thoroughly studied, nor have bone marrow-derived MSC (BM-MSC) and adipose-derived MSC (Ad-MSC) been directly compared for their immune modulatory potency or pathway utilization. Therefore, canine BM-MSC and Ad-MSC were generated in vitro and their potency in suppressing T cell proliferation and cytokine production was compared, and differential gene expression. Mechanisms of T cells suppression were also investigated for both MSC types. We found that BM-MSC and Ad-MSC were roughly equivalent in terms of their ability to suppress T cell activation. However, the two MSC types used both shared and distinct biochemical pathways to suppress T cell activation. Ad-MSC utilized TGF-b signaling pathways and adenosine signaling to suppress T cell activation, whereas BM-MSC used cyclooxygenase, TGF-b and adenosine signaling pathways to suppress T cell activation. These results indicate that canine MSC are distinct from human and rodent MSC terms of their immune suppressive pathways, relying primarily on cyclooxygenase and TGF-b pathways for T cell suppression, rather than on NO or IDO-mediated pathways.

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“…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.…”

mentioning

confidence: 99%

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

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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Object 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.

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Transplantation of mesenchymal stem cells in a canine disc degeneration model

Cited by 214 publications

References 51 publications

Tissue engineering and the intervertebral disc: the challenges

Tissue engineering and the intervertebral disc: the challenges

Mechanisms of Immune Suppression Utilized by Canine Adipose and Bone Marrow-Derived Mesenchymal Stem Cells

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

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