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16 September 2023: Review Articles

A Review of the Role of Tendon Stem Cells in Tendon-Bone Regeneration

Junjie Chen 1EFG* , Chuanfeng Jiang 1EF* , Lu Yin 1EF* , Yingqi Liu 2EF , Yue He 3EF , Sen Li 4EF* , Huarui Shen 1FG*

DOI: 10.12659/MSM.940805

Med Sci Monit 2023; 29:e940805

Table 2 Current research on factors affecting tendon healing.

Study substancesAnimalOutcomeConclusionAuthorReferences
Hepatocyte growth factor (HGF)-induced TDSCs (TDSCs)-conditioned mediumRatsCM treatment can improve the viability and migration of tendon fibroblasts, change the expression of ECM proteins, promote the organization of tendon fibers and inhibit inflammationHGF stimulates TDSCs to secrete soluble secretion products, and conditioned medium promotes repair and functional recovery of ruptured Achilles tendons. HGF-induced TDSCs-CM has the potential to treat tendinopathyZhang[]38
Rat-isolated TDSCs are cultured in HGF mediumRatsHGF promotes TDSCs proliferation and migration, but inhibits TDSCs osteogenic differentiationHGF can promote the proliferation and migration of TDSCs and inhibit osteogenic differentiation in vitro. HGF could be used as a cytokine treatment for tendon traumaHan[]39
Hepatocyte growth factor (HGF) TDSCs (TDSCs)RatsHGF produces more CD163 M2 monocytes and IL-10 cells (anti-inflammatory) HGF produces a more ordered arrangement of collagen fibers and lower levels of COLIII, α-SMA, TGF-β1TDSCs + HGF exhibiting HGF overexpression may promote tendon healing by reducing inflammation and fibrosis, possibly in part by inhibiting TGF-β1-induced signalingZhang[]40
Hepatocyte growth factor (HGF) and insulin-like growth factor I (IGF-I)RatsThe p110β-regulated subunit and p3α-catalytic subunit of PI85K are preferentially recruited into these complexes in response to IGF-IIGF-I is more effective than HGF in stimulating phosphorylation of the protein kinase Akt/PKB downstream of PI3KHalevy[]41
Basic fibroblast growth factorDogTendons receiving basic fibroblast growth factor have increased vascular, cellular, and adhesion formation compared with tendons that undergo surgical repair aloneWhile basic fibroblast growth factor accelerates the cell proliferation phase of tendon healing, it also promotes neovascularization and inflammation at the earliest stages after tendon sutureThomo-poulos[]49
Proximal and distal stump injections of 5 μg of recombinant basic fibroblast growth factor (bFGF) white rabbit Achilles tendonNew Zealand White Rabbitcollagen fibers had significantly better orientation and organization in the study group. There was no difference in the number of fibroblasts and the degree of angiogenesis between the 2 componentsThe application of basic fibroblast growth factor at tendon repair sites improves the healing process by improving collagen fiber orientation and increasing biomechanical resistanceNajafbeygi[]50
Rabbits after transection of the medial collateral ligament of rabbits using semi-quantitative RT-PCR, during a 14-day healing periodRabbitUsing semi-quantitative RT-PCR, we observed a significant upregulation of FGFR3 expression after 2 days. By 7 days after injury, FGFR2 expression dropped to basal levels, consistent with FGFR1 and 3These results demonstrate the role of FGFR2 in fibroblast and endothelial cell proliferation of damaged ligaments and provide a window for FGF treatmentCool[]51
Platelet-derived growth factor AA (PDGF-AA)-treated miceMiceThe hydrophilicity of PLGA containing PDGF-AA (PLGA-PDGF-AA) increased, but the strength of the material did not change significantlyPLGA-PDGF-AA promotes post-tendon regeneration and is a potential adjunct to surgical tendon injury repairWang[]53
Rats with exogenous MSCs injected into a tail veinRatsSpurious fractures 10 days after surgery had more minerals, less cartilage and higher mechanical properties at 48 days. MSC populations were identified during osteotomyThe timing of mechanical stimulation affects the physical properties of the callus and the migration of MSCs to the fracture siteWeaver[]54
In 80 osteoporotic female Sprague-Dawley ratsRatsThe callus area and width and bone volume to tissue volume ratio decreased most rapidly in VGLMHFV may impair this enhancement by enhancing bone remodeling and administering ibandronate, which accelerates fracture healingHo-Chow[]55
152 ovariectomy SD rats received closed femoral fracturesRatsVMG high-density bone volume fraction, bone volume fraction, bone density and hardness were significantly higher than those of the other three groupsSDF-1-mediated MSC migration is one of the important mechanisms of LMHFV to enhance fracture healingWei[]56
RatsRatsCallus width was greater at week 2 (=0.001), callus area at weeks 1 and 5 (allOsteoporotic bone responds higher to LMHFV than normal bone and shows significantly better resultsShu-Lu Chung[]57
Rats with osteoporotic fractures induced by oophorectomyRatsCallus formation was higher in the LIPUS group at weeks 2 to 4 and lower at weeks 6 to 8. In weeks 2 to 4 and 8 there is an increase in the ossification of the skinLIPUS can accelerate osteoporotic fracture healing by enhancing callus formation, angiogenesis, and callus remodelingCheung[]58
Primary rat MSCs are harvested in bone marrow, cultured in medium containing dexamethasone and directly inoculated with scaffoldsRatsCells with calcium deposited on decellularized scaffolds are faster than constructs that are seeded only once on day 16. Ti/ECM/MSC constructs cultured after 213 days had a calcium content of 2.13 (±6.16) μg/constructIn vitro synthesized bone-like ECMs can enhance osteoblast differentiation of MSCsDatta[]64
Decellularized lung scaffolds for natural rodent lungNatural rodentsCHAPS-based decellularization results in retention of elastin in the decellularized matrix, while SDS-based decellularization results in loss of elastin in the decellularized matrixThe importance of collagen and elastin in lung mechanics. With SDS decellularization, the mechanical integrity of the scaffold is significantly reduced and there is some loss of elastic functionPetersen[]65
Smooth muscle cells (SMCs) in 3-dimensional engineered tissuesThe rate of elastin produced by SMCs on polyglycolic acid (PGA) scaffolds is 5.1±1.11 times higher than that of type I collagen sponges. In contrast, collagen production on type I collagen sponges was 3.3±1.1 times higher than that of PGA scaffolds3-dimensional smooth muscle-like tissue can be generated by culturing SMCs on 3-dimensional scaffolds, and the phenotype of SMCs is strongly regulated by stent chemistry. These engineered tissues provide novel three-dimensional models to study cell interactions with ECM in vitroKim[]67
Decellularized vascular stromaAfter spinning the cell culture for 120 weeks, fibroblasts infiltrate approximately 40 μm into the elastin scaffold and approximately 4 μm into the collagen scaffoldBoth scaffolds are completely decellular/they are highly biodegradable/fibroblasts adhere to the scaffold surface and proliferate, with excellent cell viabilityLu[]68
Rabbit conjunctival fibroblastsRabbitOriented scaffolds exhibit lower cell adhesion but higher cell proliferation due to the orientation of the fibers compared to random scaffoldsThe arrangement of fibers can control cell orientation and enhance the interaction between cell bodies and fibers in the fiber longitudinal directionZhong[]69
Binding microchannels that allow nutrient-rich medium to flow through collagen-based scaffoldsTransmission electron microscopy analysis revealed that the size of the mineral crystals was approximately 180×80×20 nm, indicating that the crystals were located in the microfiber gap. Electron diffraction indicates that the mineral is in the HA phase, and infrared spectroscopy confirms the substitution of type A carbonatesAppropriately sized microchannels within collagen-HA scaffolds bring us closer to meeting the mass transport requirements of osteoblasts living deep within the scaffoldSachlos[]70
A thin film consisting of PBT or PBTAT and engineered spider silk protein (eADF4 (C16))Human MSC sculptured on thin films mineralized with calcium phosphate show enhanced levels of alkaline phosphatase activityThis suggests that this composite has potential uses for bone tissue engineeringHardy[]72
HGF – hepatocyte growth factor; LIPUS – low-intensity pulsed ultrasound; MSCs – mesenchymal stem cells; ECM – extracellular matrix; TDSCs – tendon stem cells; SMCs – smooth muscle cells.

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750