Table 2. A summary of the literature review as regards the effect of micro-environment on growth and survival of stem cells.
| Reference | Type of study | Cell source | Intervention | Outcome |
|---|---|---|---|---|
| Hudson et al. (98) | In vitro | hMSCs | Hypoxic (5% O2) versus normoxic (21% O2) conditions | Hypoxic expansion of human MSCs enhances 3D maturation of tissue engineered IVDs |
| Adesida et al. (99) | In vitro | hBM-MSCs | Hypoxic conditions (3% O2) versus normoxic conditions (21% O2) | Hypoxic conditions augment the chondrogenic potential of hBM-MSCs |
| Clarke et al. (100) | In vitro | hAD-MSCs and hBM-MSCs | Media supplemented with TGF-β3, GDF5, or GDF6 | GDF6 stimulation of AD-MSCs induces differentiation to an NP-like phenotype and results in a more proteoglycan-rich matrix with less stiff composition |
| Kumar et al. (101) | In vitro | hMSCs | Hypoxic (2% O2) chondrogenic media versus normoxic non chondrogenic media | MSCs enhanced differentiation into NP phenotypes with elevated expression levels of aggrecan and collagen II under hypoxic conditions |
| Elabd et al. (105) | Human in vivo study | hBM-MSCs | Hypoxic (5% O2) conditions | MRI radiological evaluation and quality of life questionnaire as an outcome measures showed significant improvement |
| Stolzing et al. (106) | In vitro | Rat nonadherent BM-MSCS | Different glucose levels in cultures | Culture in high-glucose-containing medium had a negative effect on colony formation and differentiation |
| Liang et al. (107) | In vitro | hAD-MSCs | Age (cells from mature and young male donors), glucose, acidity and osmolarity | Low glucose is a positive factor but high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of hAD-MSCs. Age did not affect the results |
| Wuertz et al. (108) | In vitro | Rat BM-MSCs | Age (cells from mature and young male donors), glucose, acidity, osmolarity and combined conditions | IVD-like glucose conditions stimulated aggrecan and collagen-1 expression. IVD-like osmolarity and pH strongly decreased proliferation and expression of matrix proteins. Osmolarity and pH dominated the effects of glucose |
| Mavrogonatou and Kletsas (109) | In vitro | Bovine-NP cells | High osmolality | |
| Liang et al. (110) | In vitro | hAD-MSCs | Low glucose, acidity, high osmolarity, and combined conditions | Low glucose is a positive factor but high osmolarity and low pH are deleterious factors that affect the survival and biological behaviors of AD-MSCs |
| Tao et al. (111) | In vitro | Rat NPCs, NP-MSCs and co-culture | High osmolality | High osmolarity inhibited cell viability and decreased the expression of aggrecan and collagen II at the mRNA and protein levels |
| Wuertz et al. (112) | In vitro | Rat BM-MSCs | Acidity | Acidity caused an inhibition of aggrecan, and collagen I, as well as a decrease in proliferation and viability and was associated with a change in cell morphology |
| Purmessur et al. (115) | In vitro | Porcine NCs | Dynamic pressurization | NP tissue maturation was induced from dynamic hydrostatic pressurization |
| Yurube et al. (116) | In vitro | Rat IVD cells | Static pressurization | Static compression-induced disc cell death and degeneration |
| See et al. (117) | In vitro | Rabbit BM-MSCs | Compressive mechanical stimulation | Extensive remodeling and ECM production occurred within the simulated IVD-like assembly |
| Dai et al. (118) | In vitro | Rats AD-MSCs | Dynamic compression and NPCs co-culture | Combination of dynamic compression and coculture showed an additive effect on NP-like cell differentiation |
| Li et al. (120) | In vitro | Rat NPCs | Priming with rGDF-5 | rGDF-5 treatment of disc cells from the GDF-5-deficient mice resulted in a dose-dependent upregulation of the aggrecan and type II collagen genes |
| Chujo et al. (121) | In vitro and animal in vivo study (rabbit model) | Bovine NP and AF cells, rat IVD model |
rhGDF-5 | In vitro, rhGDF-5 increased the DNA and proteoglycan contents. In vivo, the injection of rhGDF-5 improved disc height, MRI scores and histologic grading scores |
| Stoyanov et al. (123) | In vitro | hBM-MSCs | TGFß or GDF5 or coculture with bovine NPCs. All groups were incubated at low (2%) or normal (20%) oxygen | Hypoxia and GDF5 led to directing MSCs towards the IVD-like phenotype |
| Wehling et al. (127) | In vitro | hBM-MSCs | IL-1beta and TNF alpha | Both IL-1beta and TNF alpha inhibited chondrogenesis in a dose-dependent manner |
| Steck el al. (134) | In vitro | hBM-MSCs | TGF beta-3, dexamethasone, and ascorbate | After TGF beta mediated differentiation, MSC adopted a gene expression profile that resembled native IVD tissue more closely than native joint cartilage |
| Thompson et al. (137) | In vitro | Canine IVD disc | ILGF-1, EGF, FGF, or TGF beta-3 | TGF beta-3 and EGF elicited greater proliferative responses than FGF; ILGF-1 produced a marginally significant response in the nucleus and no response in the anulus and transition zone |
| Walsh et al. (138) | In vivo | Murine IVD disc | GDF-5, TGF beta-3, ILGF-1 or basic FGF | A statistically significant increase in disc height 4 weeks after GDF-5 treatment was measured |
| Li et al. (140) | In vitro | Rat AF cells | BMP-2 | BMP-2 increases aggrecan and collagen type II mRNA expression. BMP-2 also up-regulates mRNA expression for BMP-7 and TGF beta-3 |