Table 2.
Effects of extrinsic mechanical cues on MSC differentiation
| Study | Cell source | Culture conditions | Loading conditions | Key findings |
|---|---|---|---|---|
| Fluid flow | ||||
| Bancroft et al. (2002) | Rat marrow | 3D Ti mesh | Perfusion @ 0.3–3 mL min−2, 16 day | Increased calcium content and matrix distribution |
| Li et al. (2004) | Human marrow | 2D Glass slide | Parallel plate, 2 h, 1 Hz, peak shear of 10 dyn cm−2 | Increased osteopontin and osteocalcin mRNA, no change in Col 1 and CBF‐1 mRNA |
| Knippenberg et al. (2005) | Goat adipose | 2D Glass slide | Parallel plate, 1 h, 5 Hz, mean shear of 0.6 Pa | Increased NO and COX‐2, decreased ALP, no change in osteopontin or Col 1 mrNA |
| Datta et al. (2006) | Rat marrrow | 3D Ti or Ti/ECM mesh | Perfusion @ 1 mL min−1, 16 day | Larger increase in mineralization in Ti/ECM |
| Riddle et al. (2006) | Human marrow | 2D Glass slide | Parallel plate, ≤ 120 min, 1 Hz, shears of 5–20 dyn cm−2 | Increased ERK 1/2 activation and calcineurin activity |
| Arnsdorf et al. (2009b) | C3H/10T1/2 | 2D Fibronectin‐coated glass slide | Parallel plate, 1 h, 1 Hz, peak shear of 10 dyn cm−2 | Increased Runx2, Sox9 and PPARγ, RhoA and ROCKII regulates OFF‐induced osteogenesis |
| Huang et al. (2010) | Rat marrow | 2D Glass slide | Parallel plate, 24 h, shears of 5–20 dyn cm−2 | Increased cardiomyogenic mRNA and protein markers |
| Hydrostatic Pressure | ||||
| Angele et al. (2003) | Human marrow | Aggregate | 4 h day−1, 1–7 day, 1 Hz, 5.03 MPa | Increased proteoglycan and collagen content |
| Elder et al. (2005) | C3H/10T1/2 | Aggregate | 1800 or 7200 cycles day−1, 3 day, 1 Hz, 5 MPa (10 min on, 10 min off) |
1800 cycles: no differences 7200 cycles: increased sGAG content and collagen synthesis |
| Miyanishi et al. (2006a) | Human marrow | Pellet | 4 h day−1, 3–14 day, 1 Hz, 10 MPa | Increased Sox9, Col II and Agc mRNA; Col II and Agc matrix synthesis |
| Miyanishi et al. (2006b) | Human marrow | Pellet | 4 h day−1, 3–14 day, 1 Hz, 0.1–10 MPa | Increased Sox9, Agc, Col II mRNA; dose/time‐dependent increase in sGAG and collagen synthesis |
| Finger et al. (2007) | Human marrow | 2% Agarose | 4 h day−1, 14 day, 1 Hz, 7.5 MPa | Increased Sox9 mRNA, no change in Col II and Agc mRNA, time‐dependent increase in Col I |
| Luo & Seedhom (2007) | Ovine marrow | Polyester | 30 min day−1, 10 day, 0.25 Hz, 0.1 MPa | Increased sGAG and collagen content |
| Wagner et al. (2008) | Human marrow | Collagen I Sponge | 4 h day−1, 10 day, 1 Hz, 1 MPa | Increased proteoglycan content and Sox9, Agc and Col II mRNa; no change in Runx2 or TGF‐β1 mRNA |
| Li et al. (2009) | Rat marrow | 1.5% Alginate | 1 h day−1, 7 day, 0.25 Hz, 36 kPa | Increased Sox9, Runx2, Ihh, Agc and Col II mRNA |
| Ogawa et al. (2009) | Human adipose | Collagen I Sponge | 1 week, 0.5 Hz, 0.5 MPa | Increased Sox9, Agc, Col II and Col X mRNA, |
| Zeiter et al. (2009) | Bovine marrow | Aggregate | 3 h day−1,14 day, 1 Hz, 3 MPa | No change in Sox9, Agc, Col I, Col II mRNA or sGAG synthesis |
| Meyer et al. (2011) | Porcine marrow | 2% Agarose | 1 h day−1, 42 day, 1 Hz, 10 MPa | Increased sGAG and collagen content in donor‐dependent manner |
| Steward et al. (2012) | Porcine marrow | 2% Agarose or fibrin | 4 h day−1, 21 day, 1 Hz, 10 MPa | Increase in sGAG synthesis in fibrin gels only |
| Vinardell et al. (2012) | Porcine synovial membrane and fat pad | Pellet | 4 h day−1, 14 day, 1 Hz, 10 MPa | Increased Sox9 mRNA @ 1 ng mL−1 TGF‐β3 but not at 10 ng mL−1; decreased Ihh and Col X in synovial membrane cells |
| Steward et al. (2013) | Porcine marrow | 1 or 4% Agarose | 4 h day−1, 21 day, 1 Hz, 10 MPa | Increased sGAG synthesis, Sox9, Agc, Col II mRNA and vimentin organization in 4% gels only |
| Carroll et al. (2014) | Porcine marrow and fat pad | 2% Agarose | 4 h day−1, 35 day, 1 Hz, 10 MPa | Increased sGAG synthesis in both cell types, suppressed mineralization in bone marrow |
| Compression | ||||
| Takahashi et al. (1998) | Limb bud | Collagen gel | 20–30% strain | Increased Sox9, Agc and Col II mRNA; suppressed IL‐1β |
| Huang et al. (2004) | Rabbit marrow | 2% Agarose | 4 h day−1, 14 day, 1 Hz, 10% strain | Increased Agc, Col II and TGF‐β1 mRNA |
| Campbell et al. (2006) | Human marrow | 3% Alginate | 1.5 h on/4.5 h off, 8 day, 1 Hz, 15% strain | Increased Sox9, Agc, Col II and Col X mRNA; complex interplay between DC and TGF‐β1 supplementation |
| Mauck et al. (2006) | Bovine marrow | 2% Agarose | 3 h day−1, 5 day, 1 Hz, 10% strain | Increased Agc mRNA and sGAG synthesis |
| Mouw et al. (2007) | Bovine marrow | 3% Agarose | 3 h day−1, on day 8 or 16, 1 Hz, 10% strain | Increased sGAG synthesis, and Agc, Col I and Col II mRNA on day 16; stronger with addition of TGF‐β1 |
| Thorpe et al. (2008) | Porcine marrow | 2% Agarose | 1 h day−1, 42 day, 0.5 Hz, 10% strain | Decreased, sGAG and Col II synthesis |
| Kisiday et al. (2009) | Equine marrow | 2% Agarose | 45 min on/45 min off day−1, 15 or 21 day, 0.3 Hz, 7.5–10% strain | DC w/o TGF‐β1 increased sGAG synthesis, DC w/TGF‐β1 decreased sGAG synthesis |
| Pelaez et al. (2009) | Human marrow | Fibrin gels | ||
| Kupcsik et al. (2010) | Human marrow | Fibrin‐polyurethane gels | 1 h day−1, 7 day, 1 Hz, 10–20% strain | Increased sGAG synthesis and Agc, Col II, Col X, TGFB1 and TGFB3 mRNA; effects stronger at lower TGF‐β1 concentrations |
| Li et al. (2010a) | Human marrow | Fibrin‐polyurethane gels | 1 h day−1, 7 day, 1 Hz, 10–20% strain | Increased sGAG, TGF‐β1 and TGF‐β3 synthesis, and Agc, Col II and Col X mRNA; effects stronger at lower TGF‐β1 concentrations |
| Li et al. (2010b) | Human marrow | Fibrin‐polyurethane gels | 1 h day−1, 7 day, 0.1 or 1 Hz, 10–15, 20 or 30% strain | Higher frequency and amplitude = increased sGAG synthesis and chondrogenic gene expression |
| Haugh et al. (2011b) | Porcine marrow | 2% Agaorse | 1 h day−1, on day 7, 14 or 21, 1 Hz, 10% strain | Increased Agc, Col I and Col II mRNA in temporal and spatial‐dependent manner |
| Thorpe et al. (2012) | Porcine marrow | 2% Agarose or fibrin | 3 h day−1, 1 Hz, 21 or 42 days |
Day 21: decreased markers of chondro/myogenesis in both gels Day 42: increased chondrogenic markers in fibrin gels |
| Steward et al. (2014) | Porcine marrow | 1% or 4% Agarose | 1 h day−1, on day 7, 14 or 21, 1 Hz, 10% strain | Increased Sox9, Agc and Col II in 4% gels relative to 1%; inhibition of integrins abrogated this response |
| Tension | ||||
| Sumanasinghe et al. (2006) | Human marrow | Collagen matrix | 4 h day−1, 7 or 14 day, 1 Hz, 0,10, or 12% strain | Increased BMP‐2 mRNA when exposed to 10% (day 7/day 14) and 12% strain (day 14) |
| Ward et al. (2007) | Human marrow | Collagen matrix | 3–5% strain | Increased mineralization, osteogenic mRNA, ERK1/2 activation; decreased chondrogenic, adipogenic, neurogenic expression |
| McMahon et al. (2007) | Rat marrow | Col‐GAG scaffold | 7 day, 1 Hz, 10% strain | Increased sGAG synthesis rate |
| Byrne et al. (2008) | Rat marrow | Col‐GAG scaffold | 4 h day−1, day 5–7, 1 Hz, 5% styrain | Increased osteopontin mRNA |
| McMahon et al. (2008) | Rat marrow | Col‐GAG scaffold | 7 day, 1 Hz, 10% strain | Increased sGAG synthesis rate; dependent on stretch‐activated calcium channels |
| Qi et al. (2008) | Rat marrow | Plastic strip | 40 min, 0.5 Hz, 2000 με | Increased ALP activity, and Cbfa1 and Ets‐1 mRNA |
| Hanson et al. (2009) | Human adipose | Col‐coated BioFlex™ dish | 4 h day−1, 14 day, 1 Hz, 10% strain | Increased amount and rate of calcium deposition |
| Haudenschild et al. (2009) | Human marrow | 2% Alginate | 24 h, 0.2 Hz, 10% strain | Increased osteogenic gene expression and decreased chondrogenic gene expresson |
| Sumanasinghe et al. (2009) | Human marrow | Collagen matrix | 4 h day−1, 7 or 14 day, 1 Hz, 0, 10 or 12% strain | Increased IL‐6 and IL‐8 expression in 10/12% strain |
| Kearney et al. (2010) | Rat marrow | Col‐coated silicone | 14 day, 0.17 Hz, 2.5% strain | Increased Cbfa1, Col I, osteocalcin, BMP2 mRNA; stretch‐activated ion channels needed for Col I increase; ERK, p38 and PI3 needed for BMP increase |
| Jang et al. (2011) | Rabbit marrow | Silicone wafer | 3 day, 0.26 Hz, 3 and 10% strain | Increased ALP and α‐SMA |
| Rui et al. (2011) | Rat tendon | Col‐coated silicone | 0.5 Hz, 0, 4 or 8% strain | Increased BMP‐2 expression and mRNA, ALP activity and calcium deposition |
DC, dynamic compression; ECM, extracellular matrix; ERK, extracellular signal‐regulated kinase; HP, hydrostatic pressure; RhoA, RhoA GTPase; ROCK, Rho kinase; TGF, transforming growth factor.