Table 3.
Effect of GDF family members on MSCs in culture
| Cell Population | GDF Family Member/ Concentration | Culture Conditions | Culture Duration | Outcomes | Ref. |
|---|---|---|---|---|---|
| hMSCs | GDF5 | Pellet | i) Significantly increased sGAG and type II collagen production. ii) Increased alkaline phosphatase, types I and X collagen and osteopontin secretion. |
Bai et al151 | |
| hMSCs | GDF5 (50‐500 ng/mL) | Pellet | 21 Days | i) Significantly upregulated collagen II. ii) Potential synergistic relationship with TGFβ1 in driving chondrogenic differentiation. iii) No effect on cell proliferation. iv) Concentration of 300 ng/mL found to be most effective. |
Coleman et al158 |
| Murine Limb bud (E10) + C3H10T1/2 | GDF5 (10‐500 ng/mL) | Pellet | Up to 4 Days | i) Significantly increased collagen II and Sox9 expression ii) Significantly increased cell proliferation (after 24 hours). iii) Increased condensation of limb bud cells at 100‐500 ng/mL, stained positively with alcian blue after 3 days culture. |
Hatakeyama et al159 |
| hMSCs | GDF5 (10‐100 ng/mL) | Woven 3D PLGA scaffolds | 12 Days | i) Significantly increased scaffold cellularity. ii) Did not increased collagen production. |
Jenner et al160 |
| hMSCs and hASCs | GDF5 (10‐1000 ng/mL) | Pellet, 3D collagen I scaffold | 14 Days | i) Significantly upregulated collagen II, sox9 and aggrecan expression. Upregulated NP‐specific marker genes (Keratins 8, 18, 19) though not as dramatically. ii) 100 ng/mL most effective. iii) ASCs more responsive than MSCs, some NP‐specific genes not upregulated (CAXII, Brachyury) |
Clarke et al161 |
| hMSCs | GDF5 (100 ng/mL) | Pellet, followed by agarose mold | 7 Days, followed by up to 28 Days cartilage formation | i) Significantly increased aggrecan expression but not collagen II or Sox9. ii) No evidence of hypertrophic marker expression. iii) Evidence of synergy with TGFβ1 to promote chondrogenic differentiation. |
Murphy et al162 |
| Rabbit ASCs | GDF5 (10‐200 ng/mL) | 2D and 3D collagen I sponge | 21 Days 2D/ 28 Days 3D | i) In 2D, 100 ng/mL induced collagen II, aggrecan and collagen I expression. 100 to 200 ng/mL most effective. ii) Collagen X expression observed after 21 days. iii) In 3D, GDF5 significantly increased collagen II and aggrecan but also collagen I and X. 3D inducti.on was more potent than 2D |
Han et al163 |
| hMSCs | GDF5 (100 ng/mL) | 3D alginate bead | Up to 18 Days | i) Significantly upregulated aggrecan, collagen II. ii) Promoted high expression of aggrecan in relation to collagen. |
Gantenbein‐Ritter et al164 |
| hMSCs and hASCs | GDF6 (10‐1000 ng/mL) | Pellet, 3D collagen I scaffold | 14 Days | i) Significantly upregulated collagen II, sox9 and aggrecan expression. Upregulated NP‐specific marker genes (Keratins 8, 18, 19, CAXII, Brachyury) in MSCs and ASCs and to greater extent than TGFβ1 GDF5. ii) 100 ng/mL most effective. iii) Increased sGAG secretion and NP‐like proteoglycan: collagen ratio. |
Clarke et al161 |
| hMSCs | GDF6 (10 ng/mL) | 3D collagen I gels, PLA constructs | Up to 14 Days | i) No evidence of collagen X or collagen II response to GDF6 stimulus. Ii) No MMP expression response. |
Heckmann et al165 |
| C3H10T1/2 | GDF6 (adenoviral transfection) | 2D | Up to 21 Days | i) Stimulated proliferation. ii) Significantly upregulated collagen II, aggrecan but not collagen X or osteocalcin. iii) 2‐fold increase in GAG secretion vs controls. |
Nochi et al166 |
Abbreviations: GDF, growth differentiation factor; hASCs, human adipose‐derived mesenchymal stem cells; hMSCs, human bone marrow‐derived mesenchymal stem cells; PLGA, poly (lactic‐co‐glycolicacid); sGAG, sulphated glycosaminoglycan; sox9, sex determining region Y‐Box9.