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Author | Animal model | Degeneration model | Cells transplanted | Method of cell administration | Results/conclusions |
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Crevensten et al. [38] | Rat | Needle puncture | Allogeneic MSCs | Intradiscal injection of MSCs with 15% hyaluronan gel | MSCs: (i) Trend towards increased disc height (ii) Retained in disc, remain viable, and can proliferate for at least 28 days |
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Ganey et al. [39] | Canine | Partial nucleotomy | Non culture expanded autologous adipose derived stem cells | Intradiscal injection with HA | Transplantation of adipose MSCs improved: (i) MRI T2 signal at 12 months (ii) Disc histology assessment (iii) Increase collagen II expression |
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Ghosh et al. [40] | Sheep | Chondroitinase-ABC injection | Allogeneic Stro-3+ Mesenchymal Precursor Cells (MPCs) | Injection with hyaluronic acid (Euflexxa) carrier | MPCs + HA: (i) Restore disc height (ii) Improved MRI Pfirrmann scores (iii) Improved histological degeneration scores (iv) Restoration of extracellular matrix |
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Hee et al. [41] | Rabbit | Axial loading | Allogeneic bone marrow MSCs | Injection of MSCs combined with axial distraction | (i) MSCs increase disc height and improve histology scores (ii) MSCs Survive for 8 weeks |
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Henriksson et al. [42] | Porcine, minipig | Nucleotomy | Xenogeneic Human MSCs | Xenotransplantation of hMSCs with Puramatrix hydrogel carrier or F12 media suspension. | MSCs: (i) Survive in pig disc space for 6 months (ii) Differentiated into cells representing disc chondrocytes (iii) Improved MRI appearance in MSC/hydrogel treatment groups (iv) Combination of with Puramatrix hydrogel increased cell differentiation, matrix production and survival (v) At three and six months expressed SOX9, aggrecan, and collagen II |
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Hiyama et al. [43] | Canine | Nucleotomy | Autologous MSCs | Percutaneous injection of MSCs infected with AcGFP1 retrovirus vector. | MSCs: (i) Increased disc height and MRI T2 signal (ii) Increased production of proteoglycans (iii) Improved histological structure including AF (iv) Proportion of FasL-positive cells increased following MSC injection |
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Ho et al. [44] | Rabbit | Percutaneous needle puncture | Autologous MSCs | Intradiscal injection of BrdU-labelled MSCs | MSCs: (i) Found in disc at 16 weeks post injection (ii) Discs injected at 6 months post nucleotomy less degenerate than controls but not returned to baseline (iii) Increased PG in posterior inner annulus (iv) Did not restore disc height (v) Only partial arrest possible following administration and more effective at later point of degeneration |
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Hohaus et al. [30] | Canine | Annular injury and partial nucleotomy | Autologous adipose derived MSCs | Intradiscal injection | Adipose MSCs (i) Remain viable in disc (ii) Maintain disc morphology, disc height, and MRI T2 signal (iii) HA alone insufficient to prevent degeneration |
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Jeong et al. [45] | Rat | Annular injury | Xenogeneic human MSC | Intradiscal injection | MSCs: (i) Maintain disc height and T2 signal (ii) Restore AF structure (iii) Survive for 2 weeks after injection but not 4 weeks |
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Jeong et al. [46] | Rat | Needle injection | Xenogeneic adipose derived human MSCs | Intradiscal injection | MSCs: (i) Less loss of disc height following injection (ii) Restore T2 MRI signal (iii) Restore AF structure (iv) Upregulate collagen 2 and aggrecan |
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Miyamoto et al. [47] | Rabbit | NP aspiration | Autologous synovial MSCs | Intradiscal injection | MSCs: (i) Identified in NP at 24 weeks (ii) Preserve disc height (iii) Preserve MRI T2 signal for 6 weeks (iv) Preserve NP histological structure (v) Increase expression of collagen-II |
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Murrell et al. [48] | Rat | NP aspiration | Xenogeneic human olfactory neurosphere-derived stem cells | Intradiscal injection | (i) 70% cells identified in discs (ii) Cells assumed NP cell like phenotype |
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Omlor et al. [49] | Porcine | Partial nucleotomy | Autologous Bone marrow MSCs | Injection of MSCs transfected with Rv-eGFP within fibrin glue |
(i) After 3 days only 9% of injected cells remained in disc |
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Prologo et al. [50] | Porcine | Needle biopsy of disc | Xenogeneic human MSCs | Xenogenic percutaneous administration of iodine-124 2′-flouro-2′ –deoxy-1B-D-arabinofuranosyl-5-iodouracil –labeled hMSCs | (i) PET-CT confirmed cells in NP on day 0 and day 3 following injection. (ii) Immunohistological staining at 15 days confirmed presence of cells in treated discs |
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Sakai et al. [51] | Rabbit | Nucleotomy – NP aspiration. | Autologous MSCs | MSCs embedded in atelocollagen hydrogel | MSCs: (i) Preserved histological structure (ii) Retained and proliferated in disc (iii) Increased PGs on histological staining |
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Sakai et al. [52] | Rabbit | Nucleotomy – NP aspiration. | Autologous bone marrow MSCs | GFP labelled MSC injection | (i) MSCs present in NP at up to 48 weeks (ii) GFP positive cells expressed collagen II, aggrecan, suggesting site dependent differentiation (iii) MSCs increased PG content of NP to baseline (iv) Increased collagen II and aggrecan mRNA, decreased collagen I following MSC injection |
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Sakai et al. [53] | Rabbit | Nucleotomy – NP aspiration. | Autologous bone marrow MSCs | MSCs embedded in atelocollagen hydrogel | (i) MSCs increased disc height and MRI T2 signal (ii) MSCs preserve histological structure, including AF (iii) Restoration of PGs suggested from immunohistochemistry and gene expression |
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Serigano et al. [54] | Canine | NP Aspiration | Autologous bone marrow MSCs | Intradiscal injection | (i) MSCs significantly increase DHI and MRI T2 signal (ii) 106 and 107 cell doses showed improved NP and inner annular histological structure (iii) 105 dose group had more degenerative changes (iv) 106 dose group had less apoptosis than 105 or 107 groups (v) 106 dose group had more live cells at 16 weeks compared to other groups |
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Sheikh et al. [55] | Rabbit | Needle puncture | Xenogeneic murine ESCs were cultured with cis-retinoic acid, transforming growth factor beta, ascorbic acid, and insulin-like growth factor | Intradiscal injection | (i) Discs treated with ESCs demonstrated increased population of new notochordal cells |
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Sobajima et al. [56] | Rabbit | Normal discs | Allogeneic MSCs | Injection with MSCs retrovirally transfected with lacZ marker gene. | (i) MSCs detected up to 24 weeks following transplantation. (ii) No inflammatory response observed in discs following MSC injection (iii) At 24 weeks more cells located in transition zone and inner AF, taking on more spindle shaped appearance (iv) Synergism with NPCs and MSCs to increase GAG production, most at 75 : 35 MPC/MSC ratio |
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Vadalà et al. [57] | Rabbit | Needle Stab | Allogeneic bone marrow MSCs | Intradiscal injection | (i) No evidence of regeneration at 9 weeks on MRI (ii) X-ray demonstrated osteophyte formation in treated discs (iii) No cells found in NP using GFP label |
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Wei et al. [58] | Rat | Nil | Xenogeneic human bone marrow MSCs – CD34− (MSCs) and CD34+ (Haemopoeitic cells) bone marrow cells | Intradiscal injection | (i) CD34− cells (MSCs) remain in NP for 42 days (ii) CD34+ cells not visible after day 10 (iii) CD34− cells expressed CTO/collagen II or CTO/Sox-9 indicating chondrocytic phenotype differentiation (iv) No inflammatory cells visible |
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Yang et al. [59] | Mouse | Annular puncture | Allogeneic bone marrow MSCs | Intradiscal injection | MSCs: (i) Preserve NP and AF structure up to 24 weeks (ii) Preserve disc height (iii) PGs upregulated (iv) Decrease in Col2a1, aggrecan and Sox9 arrested (v) GAG/DNA increased (vi) Underwent chondrocytic differentiation (vii) Increased notochordal cells suggesting MSCs promote NCC survival and proliferation (viii) Cells survive 24 weeks using GFP labelling |
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Yang et al. [60] | Rabbit | Needle puncture and nucleotomy | Autologous MSCs | Injection of MSCs with pure fibrinous gelatin-transforming growth factor-beta1 (PFG-TGF-beta1) | (i) MSCs inhibited apoptosis (ii) MSCs slowed the rate of loss of DHI and increased T2 signal at 12 weeks (iii) Increased type II collagen in MSC treated group |
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Zhang et al. [61] | Rabbit | Normal discs | Allogeneic bone marrow MSCs | Injection of LacZ labelled MSCs | (i) MSCs survive in disc (ii) MSCs increase expression of Type II collagen and PGs |
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