Copyright ©The Author(s) 2023.
World J Stem Cells. May 26, 2023; 15(5): 369-384
Published online May 26, 2023. doi: 10.4252/wjsc.v15.i5.369
Table 1 Growth factors, cytokines, and their effects on the differentiation of mesenchymal stem cells
Cell dource
FGFFGF-210 ng/mlBM-PACsFGF-2 did not lead to cell differentiation into a chondrogenic lineageEndo et al[9]
bFGF5 ng/mlSMSCsPromoted SMSCs chondrogenic differentiationOkamura et al[10]
bFGF0-40 ng/mlUC-MSCsbFGF did not alter osteogenic nor adipogenic differentiation potentialRamasamy et al[12]
bFGF20 ng/mlBMSCsbFGF pretreatment inhibited osteogenic differentiation of BMSCs at early stage, promoted it in the medium phase, and maintained it in the later stage during osteogenic inductionWang et al[13]
TGF-βTGF-β310 ng/mlSF-MSCsIncreased the expression levels of COL2A1, SOX9, ACAN, COL10A1Jia et al[15]
TGF-β10 ng/mlADSCsPromoted ADSCs chondrogenic differentiation but led to early hypertrophic maturationHesari et al[2]
TGF-β11, 10, 20 or 50 ng/mlBMSCsLow concentration of TGF-β1 (1 ng/ml) promoted osteogenic differentiation of BMSCs while high concentration of TGF-β1 (10 to 50 ng/ml) significantly inhibited osteogenesisXu et al[17]
TGF-β5 ng/mlBMSCsPromoted osteogenic differentiation of BMSCs but suppressed the maturation of ostroblastic MSC differentiation at the last stage of osteogenic processIgarashi et al[18]
TGF-β310 μg/LPDLSCsInduced chondrogenesisChoi et al[5]
ILIL-6100 ng/mLBMSCsPromoted BMSCs osteogenic differentiationXie et al[21]
IL-17A5-40 ng/mlBMSCsPromoted the neuronal-associated gene expression of BMSCsChen et al[24]
IL-1750 ng/mLMouse MSCsEnhanced the osteogenic differentiation of mMSCsLiao et al[22]
IL-6100 ng/mLhMSCsIL-6/soluble IL-6R promoted chondrogenic differentiation of MSCsKondo et al[20]
IL-17A50 ng/mlBMSCsInhibited osteogenic differentiation of BMSCsWang et al[23]
IL-2210 ng/mlMSCsUpregulated osteogenic and adipogenic transcription factorsEl-Zayadi et al[25]
Table 2 Micro RNA and their effects on the differentiation of mesenchymal stem cells
Cell source
micro-RNA-1286Over expressionhMSCs↓ Osteogenic differentiationZhou et al[27]
micro-RNA-223-3pLow expressionBMSCs↑ Osteogenic differentiationLong et al[28]
micro-RNA-346-5pOver expressionBMSCs↓ Osteogenic differentiationZhang et al[29]
micro-RNA-21Over expressionhucMSCs↑ Osteogenic differentiationMeng et al[4]
micro-RNA-130aOver expressionBMSCs↑ Osteogenic differentiation ↓ adipogenic differentiationLin et al[30]
micro-RNA-130bLow expressionBMSCs↑ Chondrogenic differentiationZhang et al[31]
micro-RNA-218Over expressionSDSCs↑ Chondrogenic differentiation during the eraly stageChen et al[32]
micro-RNA-495Over expressionhMSCs↓ Chondrogenic differentiationLee et al[33]
micro-RNA-30aOver expressionBMSCs↑ Chondrogenic differentiationTian et al[34]
micro-RNA-145Low expressionADSCs↑ Endothelial differentiationArderiu et al[26]
micro-RNA-124Over expressionADSCs↑ Neuronal differentiationMondanizadeh et al[35]
micro-RNA-10-5pLow expressionBMSCs↑ Myocardial differentiationLi et al[36]
micro-RNA-499a-5pOver expressionBMSCs↑ Cardiomyogenic differentiationNeshati et al[37]
Table 3 Physical stimuli and their effects on the differentiation of mesenchymal stem cells
Physical stimuli
Cell source
EMF1 mT, 15 Hz, 4 h/dayBMSCsBMSCs pretreated with EMF exhibited stronger osteogenic and chondrogenic differentiation potential and weaker adipogenesis capacityTu et al[40]
25, 50, 75Hz square and sinusoidal waveform EMFBMSCsEMF induced BMSCs differentiation to neuron cells in all treatment groupsAsadian et al[42]
1 mT, 15 Hz, 4 h/dayRabbit MSCsEMF enhanced the osteogenic potential of MSCsWang et al[41]
PEMFMSCsBrief exposure to low amplitude PEMFs enhanced the ability of MSCs to produce and secrete paracrine factors capable of promoting cartilage regenerationParate et al[43]
SMG30 g for 72 h or 10 daysAdult rat MSCsA shorter period of SMG promoted MSCs to differentiate into endothelial, neuronal and adipogenic cells. In comparison, a longer period of SMG promoted MSCs to differentiate into osteoblastsXue et al[48]
10 rpm, 72 h, 0.001 GBMSCsInhibited osteogenic differentiation of MSCsLiu et al[47]
30 rpm clinorotation, 3 dAdult rat MSCsPromoted the neuronal differentiation of rat MSCsChen et al[44]
7 rpm, 21 dhMSCsLowered the chondrogenic potential of hMSCsMayer-Wagner et al[50]
Microgravity0.001 GhMSCsmicrogravity-cultured hMSCs showed a better ability to differentiate into osteoblasts and adipocytes compared to cells cultured under natural gravity conditionsNakaji-Hirabayashi et al[46]]
Spare microgravityhMSCsSpare microgravity reduced the osteogenic differentiation of hMSCs and shifted the osteogenesis of hMSCs into adipogenesis, even during ostergenic inductionZhang et al[49]
FSS0.375 dyn/cm2, 2 h/dBMSCsPromoted osteogenesis-related genes and proteins in BMSCsJiang et al[54]
0.06 dyn/cm2, 6 h/dBMSCsProper FSS stimulation obviously enhanced BMSCs osteogenesis, while the expressions of osteogenic genes decreased with higher intensity of FSSJing et al[51]
0.5, 0.8 Pa, 3 h/dMSCsPromoted MSCs ostegenesisJiao et al[55]
3-7 dynes/cm2hMSCsEnhanced osteogenic differentiation Zhao et al[52]
4.2 dynes/cm2hMSCsFSS could lead to the osteogenic differentiation of hMSCsLiu et al[53]
ΔSS from 0 dyn/cm2 to 10 dyn/cm2MSCsFast ΔSS (0–0′) profits the chondrogenic differentiation, while Slow ΔSS (0–2′) advances osteogenic differentiationYue et al[57]
ΔSS from 0 dyn/cm2 to 10 dyn/cm2MSCsFast ΔSS (0–0′) profits the chondrogenic differentiation, while Slow ΔSS (0–2′) advances osteogenic differentiationLu et al[56]
HP10 MPa, 1 Hz, 4 h/d, 5 d/w, 3 wBMSCsHP promoted BMSCs chondrogenic differentiationSteward et al[60]
0-0.5 MPa, 0.5 HzhMSCsHP promoted the differentiation of the hMSCs toward osteogenesisHuang et al[59]
270 kPa, 1 Hz, 1 h/d, 5 d/w, 3 wBMSCsHP promoted chondrogenic differentiation of BMSCsLuo et al[64]
100 psiADSCsHP significantly increased osteogenic differentiation of AMSCsRu et al[65]
90 kPa, 1 hBMSCsHP promoted chondrogenic differentiation of BMSCsZhao et al[61]
90 kPa, 1 hBMSCsHP promoted the expression of marker genes for early osteogenic differentiation and chondrogenic differentiation of the BMSCsZhao et al[62]
Table 4 Hypoxia and their effects on the differentiation of mesenchymal stem cells
Cell source
Hypoxic culture (5%O2)BMSCs↑ Chondrogenic differentiation; ↑ adipogenic differentiationElabd et al[75]
Hypoxic culture (5.5%-6.5%O2)Balb/c mouse clonal MSCs↑ Osteogenic differentiationKim et al[74]
Hypoxic culture (50 μM CoCl2 simulation)Mice MSCs↑ Osteogenic differentiationYu et al[77]
Hypoxic culture (5%O2)ADSCs↑ Chondrogenic differentiationLee et al[76]
Hypoxic culture (1%O2)PBMSCs↑ Osteogenic differentiationYang et al[3]
Hypoxic culture (1%O2)BMSCs↓ Osteogenic differentiation; ↓ adipogenic differentiation; ↓ chondrogenic differentiationCicione et al[78]
Hypoxic culture (1%O2)BMSCs↑ Neuronal differentiationWang et al[80]
Hypoxic culture (1%O2)BMSCs↓ Osteogenic differentiationXu et al[72]
Hypoxic culture (2%O2)ADSCs↑ Tenocyte differentiationYu et al[73]
Hypoxic culture (2%O2)ADSCs↓ Osteogenic differentiationKim et al[79]
Hypoxic culture (2%O2)BMSCs↑ Osteogenic differentiationCiapetti et al[71]
Table 5 Exosomes of different cell sources and their effects on the differentiation of mesenchymal stem cells
Source and kind
Specific cargo
M1 macrophages-EVsmiRNA-21a-5pBMSCs↑ Osteogenic differentiationLiu et al[104]
M0 macrophages-EVsBMSCs↓ Chondrogenic differentiationXia et al[105]
M1 macrophages-EVsBMSCs↑ Osteogenic differentiation; ↑ adipogenic differentiation; ↓ chondrogenic differentiation
M2 macrophages-EVsBMSCs↓ Chondrogenic differentiation
M2 macrophages-EVsmiRNA-5106BMSCs;SIK2 and SIK3↑ Osteogenic differentiationXiong et al[106]
M2 macrophages-EVsmiRNA-690BMSCs↑ Osteogenic differentiation; ↓ adipogenic differentiationLi et al[107]
M0 macrophages-EVsMSCs↑ Osteogenic differentiationKang et al[108]
M1 macrophages-EVsmiRNA-155MSCs↓ Osteogenic differentiation
M2 macrophages-EVsmiRNA-378aMSCs↑ Osteogenic differentiation
M2 macrophages-EVsmiRNA-26a-5pBMSCs↑ Osteogenic differentiation; ↓ adipogenic differentiationBin-bin et al[109]
Macrophages-EVsBMSCs↓ Osteogenic differentiationSong et al[103]
Monocytes-EVsMSCs↑ Osteogenic differentiationEkström et al[110]
Osteoclasts-EVsmiRNA-324BMSCs↑ Osteogenic differentiationLiang et al[111]