Review
Copyright ©The Author(s) 2019.
World J Stem Cells. Sep 26, 2019; 11(9): 677-692
Published online Sep 26, 2019. doi: 10.4252/wjsc.v11.i9.677
Table 2 Age-related markers of tendon stem/progenitor cells
ObjectSpecies modelGroupsTendon typeMain findingsRef.
Cell morphologyHumanY-TSPC group: 28 ± 5 yr; A-TSPC group: 63 ± 14 yrAchilles tendonA-TSPC exhibit cell shape of star-like flattened, while Y-TSPCs exhibit spindle-shaped[14]
HumanY-TSPC: 28 ± 5 yr and A-TSPC: 63 ± 14 yrAchilles tendonsAged TSPCs are obviously larger in size, have more podia, spread further, and exhibit more robust actin stress fibers, and exhibit higher actin content[55]
Ratold rats: 20 mo and young rats: 8 wkAchilles tendonsAged TSPCs display a morphologies of large, flat and heterogeneous morphology, while younger cells exhibit the morphology of uniform elongated[57]
Miceyoung (2.5, and 5 mo) and aging (9 and 24 mo) micePatellar tendonsThe number of heterogeneous and cobblestone-shaped TSPCs is dramatically down-regulated with ageing, and the oldest TSPCs have only a few percent displaying the cobblestone shape[15]
Growth rateHumanY-TSPC group: 28 ± 5 yr; A-TSPC group: 63 ± 14 yrAchilles tendonA-TSPCs showed a proliferation deficit after 120 d of culture and had an early plateau phase, while Y-TSPCs didn’t exhibit the plateau[14]
Rat3–4 (young) and 24–26 mo (aged)Patellar tendonsProliferation rate is decreased and cell cycle progression is delayed with increasing age[53]
Ratthree different post-natal stages: 1 d, 7 d and 56 dAchilles tendonTSPCs-7d displayed that a higher proliferation rate than the groups of TSPCs-1d and TSPCs-56d[61]
RatEarly P5, mid P10, and late P20 and P30 passages were usedpatellar tendonsTSPCs at late P20 and P30 proliferate more rapidly than those at early P5 and mid P10[62]
Cell clonogenicityHumanY-TSPC group: 28 ± 5 yr; A-TSPC group: 63 ± 14 yrAchilles tendonAge-dependent clonogenic deficits in TSPCs are based on a decreased in the colony number and CFU efficiency with ageing[14]
HumanGroup 1: aged 20 (female) and 22 (male); group 2: aged 28 (female) and 31 (male) and Group 3: aged 49 (male) and 50 (female)Hamstring tendonsThe clonogenic potential is dramatically decreased with age; in addition, the size of the colonies was heterogeneous in patients, as the size of colonies produced by cells from aged patients was obviously larger than the colonies composed of cells from younger patients[50]
Ratthree different post-natal stages: 1 d, 7 d and 56 dAchilles tendonTSPCs-7d have an obviously higher clonogenic ability than TSPCs-1d and TSPCs-56d[61]
Ratearly P5, mid P10, and late P20 and P30 passages were usedpatellar tendonsThe colony numbers of TSPCs increase with passaging,[62]
Cell migrationHumanY-TSPC group: 28 ± 5 yr; A-TSPC group: 63 ± 14 yrAchilles tendonThe migration of TSPCs exhibits a decreasing trend with advanced age[14]
Cell differentiationRatthree different post-natal stages: 1 d, 7 d and 56 dAchilles tendonTSPCs from different time groups displays multidifferentiation capability, while the ability of TSPCs-7d is higher than TSPCs-1d and TPSCc-56d, and a similar trend is observed in the tenogenic differentiation capacity[61]
HumanY-TSPC: 25 ± 8yr, and A-TSPC: 65 ± 10 yrAchilles tendonTenogenic differentiation capacity of TSPCs significantly decreases with ageing[54]
Miceyoung (2.5, and 5 mo) and aging (9 and 24 mo) micePatellar tendonsAged TSPCs formed adipocytes more readily than younger cells and expressed higher levels of adipogenic markers[15]
Ratearly P5, mid P10, and late P20 and P30 passages were usedpatellar tendonsTSPCs tend to differentiate into osteoblasts, while the adipogenic, chondrogenic and tenogenic differentiation capacities in TSPCs decline during in vitro subculture[62]
Miceearly P0, and late P5 passages were usedAchilles tendonThe TSPCs experiences a gradual loss of tenogenic differentiation with passaging due to increased expression and activity of Hdac[65]
HumanY-TSPC group: 28 ± 5 yr; A-TSPC group: 63 ± 14 yrAchilles tendonA-TSPC have been reported to display an evident self-renewal and clonogenic decrease, multipotency is maintained in vitro[14]
HumanGroup 1: aged 20 (female) and 22 (male); group 2: aged 28 (female) and 31 (male) and Group 3: aged 49 (male) and 50 (female)Hamstring tendonsMulti-potency assays were not influenced by advanced ageing, although Y-TSPCs produced higher levels of some osteogenic and adipogenic genes, while chondrogenic genes were expressed at high levels in A-TSPCs[50]
CD markerRat3–4 (young) and 24–26 mo (aged)Patellar tendonsAged TSPCs express lower levels of CD90.1 than young cells, but higher levels of CD44[53]
Ratearly P5, mid P10, and late P20 and P30 passages were usedpatellar tendonsCD90 and CD73 is down-regulated with increasing numbers of passaging[62]
Cell stemness markerMiceyoung (2.5, and 5 mo) and aging (9, and 24 mo) micePatellar tendonsThe expression of the stem cell markers Oct-4, NS, Sca-1 and SSEA-1 in TSPCs decreased in an age-dependent manner[15]
Cell viscoelasticityRatold rats: 20 mo and young rats: 8 wkAchilles tendonsAn overall increase in G′, G″and hTSPC with ageing, revealing an important increase in stiffness of aged TSPCs[57]
humanY-TSPC: 28 ± 5 yr and A-TSPC: 63 ± 14 yrAchilles tendonsCell stiffness and size increase in A-TSPCs[55]
Cell senescence markershumanY-TSPC group: 28 ± 5 yr A-TSPC group: 63 ± 14 yrAchilles tendonA-TSPCs undergo an early appearance of cellular senescence, as determined by quantifying the number of β-gal- positive cells at different time points[14]
ratEarly P5, mid P10, and late P20 and P30 passages were usedpatellar tendonsThe significant up-regulation of β-gal activity in TSPCs with increasing passaging[62]