Table 1 |
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Therapeutic strategies to augment cell-based cartilage repair |
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Impairment |
Pathomechanism |
Therapeutic strategy |
References |
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|
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|
Differentiation insufficiencies |
Un- or dedifferentiated cells |
Timed growth factor release systems/gene delivery |
|
|
TGF-β superfamily members |
[76,85,88,134] |
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FGFs |
[131] |
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SOX/Smads |
[119-121,124-126] |
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Cell selection |
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|
Growth factor selection |
[52-54,64] |
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Immunophenotype selection |
[41,46] |
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Hypertrophic differentiation |
Inhibition of hypertrophy |
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|
BMP inhibitors: noggin, chordin, siRNAs |
[89,90,160] |
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|
PTHrP/IHH |
[81,91-95] |
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|
Wnt5a |
[29,103,163] |
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|
No dexamethasone |
[75] |
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|
Osteogenesis |
Inhibition of osteogenesis |
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|
BMP inhibitors (noggin, chordin), siRNAs |
[89,90,160] |
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|
Establishment of a barrier/tidemark to bone |
[49,198] |
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|
Senescence |
Senescence protection |
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|
Age |
Low oxygen tension |
[107,110] |
|
|
Telomere erosion |
Use of telomerized cells |
[117] |
|
|
Oxidative damage |
Anti-oxidative selenoproteins, superoxide dismutase |
[115,117,118,151,187] |
|
|
Chemical stress |
Anti-inflammatory agents (IL-1Ra, sIL-1R, sTNFR) |
[132,185-188,190,191,193-195] |
|
|
Mechanical stress |
Mechanoprotection |
[157,168,169] |
|
|
Cell loss |
Inefficient cell delivery |
Guided, homogeneous cell delivery |
[2,48] |
|
Apoptosis (NO induced, stress) |
Anti-apoptotic measures |
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|
Bcl-2, Bcl-XL, anti-FasL |
[151,161,162,164] |
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|
Anti-inflammatory agents (see also above) |
[132,185-188,190,191,193-195] |
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|
Anti-oxidative agents |
[115,117,118,151,187] |
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|
Necrosis |
Necrosis |
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|
Age |
Surgical protection (no needle stitches, no unnecessary harm to cartilage lesion borders) |
[2,48] |
|
|
Mechanical stress |
Mechanoprotection |
[2,48;168,169] |
|
|
Chemical stress |
Anti-inflammatory agents |
[132,185-188,190,191,193-195] |
|
|
Oxidative stress |
Anti-oxidative agents |
[115,117,118,151,187] |
|
|
Matrix degradation |
Matrix degradation |
Delivery of matrix components |
[197] |
|
Inflammation |
Anti-inflammatory agents (IL-1Ra, sIL-1R, ICE inhibitor, sTNFR, anti-TNF-antibodies, TACE inhibitor, TIMP-1, -2, MMP inhibitors, IL-4, -10, -11, -13, GFAT) |
[132,185-188,190,191,193-195] |
|
|
Mechanical stress (shear stresses, compressive forces) |
Mechanoprotection |
||
|
No trauma |
[2,48;168,169] |
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|
Avoidance of non-physiological loads |
[1,2,8,9,12,20] |
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|
Establishment of correct knee axis and stability |
[1,2,8,9,12,20] |
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|
Antioxidants |
[115,117,118,151,187] |
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|
Integration |
Cartilage to cartilage |
Cartilage matrix crosslinks |
[20,49,200-202] |
|
Cartilage to bone |
Tidemark formation |
[49,198] |
|
|
Stimulation of cell migration |
[27,29,66] |
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|
Chondroblasts above tidemark |
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|
Osteoblasts below tidemark |
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|
|
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BMP, bone morphogenetic protein; FasL, Fas-Ligand; FGF, fibroblast growth factor; GFAT, fructose-6-phosphatase amido transferase; ICE, IL-1 converting enzyme; IHH, indian hedgehog; IL, interleukin; IL-1Ra, IL-1 receptor antagonist; MMP, matrix metalloproteinase; NO, nitric oxide; PTHrP, parathyroid hormone related peptide; sIL-1R, soluble IL-1 receptor; siRNA, small interfering RNA; SOX, SRY (sex determining region Y)-box; sTNFR, soluble TNF receptor; TACE, TNF-alpha converting enzyme; TGF, transforming growth factor; TIMP, tissue inhibitor of matrix metalloproteinases; TNF, tumor necrosis factor. |
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Steinert et al. Arthritis Research & Therapy 2007 9:213 doi:10.1186/ar2195 |
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