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
Background
Tendon Stem Cells
Physiological Structure of Tendon Bone Tissue
Research Progress of TDSCs on Tendon-Bone Healing
Factors Affecting TDSCs Promotion of Tendon Healing
Growth Factors
Mechanical Stimulation
Biological Scaffold
The Combination of Multiple Strategies
Future Directions
Conclusions
References
Table 2 Current research on factors affecting tendon healing.
| Study substances | Animal | Outcome | Conclusion | Author | References |
|---|---|---|---|---|---|
| Hepatocyte growth factor (HGF)-induced TDSCs (TDSCs)-conditioned medium | Rats | CM treatment can improve the viability and migration of tendon fibroblasts, change the expression of ECM proteins, promote the organization of tendon fibers and inhibit inflammation | HGF 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 tendinopathy | Zhang | []38 |
| Rat-isolated TDSCs are cultured in HGF medium | Rats | HGF promotes TDSCs proliferation and migration, but inhibits TDSCs osteogenic differentiation | HGF can promote the proliferation and migration of TDSCs and inhibit osteogenic differentiation in vitro. HGF could be used as a cytokine treatment for tendon trauma | Han | []39 |
| Hepatocyte growth factor (HGF) TDSCs (TDSCs) | Rats | HGF 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-β1 | TDSCs + HGF exhibiting HGF overexpression may promote tendon healing by reducing inflammation and fibrosis, possibly in part by inhibiting TGF-β1-induced signaling | Zhang | []40 |
| Hepatocyte growth factor (HGF) and insulin-like growth factor I (IGF-I) | Rats | The p110β-regulated subunit and p3α-catalytic subunit of PI85K are preferentially recruited into these complexes in response to IGF-I | IGF-I is more effective than HGF in stimulating phosphorylation of the protein kinase Akt/PKB downstream of PI3K | Halevy | []41 |
| Basic fibroblast growth factor | Dog | Tendons receiving basic fibroblast growth factor have increased vascular, cellular, and adhesion formation compared with tendons that undergo surgical repair alone | While basic fibroblast growth factor accelerates the cell proliferation phase of tendon healing, it also promotes neovascularization and inflammation at the earliest stages after tendon suture | Thomo-poulos | []49 |
| Proximal and distal stump injections of 5 μg of recombinant basic fibroblast growth factor (bFGF) white rabbit Achilles tendon | New Zealand White Rabbit | collagen 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 components | The application of basic fibroblast growth factor at tendon repair sites improves the healing process by improving collagen fiber orientation and increasing biomechanical resistance | Najafbeygi | []50 |
| Rabbits after transection of the medial collateral ligament of rabbits using semi-quantitative RT-PCR, during a 14-day healing period | Rabbit | Using 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 3 | These results demonstrate the role of FGFR2 in fibroblast and endothelial cell proliferation of damaged ligaments and provide a window for FGF treatment | Cool | []51 |
| Platelet-derived growth factor AA (PDGF-AA)-treated mice | Mice | The hydrophilicity of PLGA containing PDGF-AA (PLGA-PDGF-AA) increased, but the strength of the material did not change significantly | PLGA-PDGF-AA promotes post-tendon regeneration and is a potential adjunct to surgical tendon injury repair | Wang | []53 |
| Rats with exogenous MSCs injected into a tail vein | Rats | Spurious fractures 10 days after surgery had more minerals, less cartilage and higher mechanical properties at 48 days. MSC populations were identified during osteotomy | The timing of mechanical stimulation affects the physical properties of the callus and the migration of MSCs to the fracture site | Weaver | []54 |
| In 80 osteoporotic female Sprague-Dawley rats | Rats | The callus area and width and bone volume to tissue volume ratio decreased most rapidly in VG | LMHFV may impair this enhancement by enhancing bone remodeling and administering ibandronate, which accelerates fracture healing | Ho-Chow | []55 |
| 152 ovariectomy SD rats received closed femoral fractures | Rats | VMG high-density bone volume fraction, bone volume fraction, bone density and hardness were significantly higher than those of the other three groups | SDF-1-mediated MSC migration is one of the important mechanisms of LMHFV to enhance fracture healing | Wei | []56 |
| Rats | Rats | Callus width was greater at week 2 (=0.001), callus area at weeks 1 and 5 (all | Osteoporotic bone responds higher to LMHFV than normal bone and shows significantly better results | Shu-Lu Chung | []57 |
| Rats with osteoporotic fractures induced by oophorectomy | Rats | Callus 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 skin | LIPUS can accelerate osteoporotic fracture healing by enhancing callus formation, angiogenesis, and callus remodeling | Cheung | []58 |
| Primary rat MSCs are harvested in bone marrow, cultured in medium containing dexamethasone and directly inoculated with scaffolds | Rats | Cells 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/construct | In vitro synthesized bone-like ECMs can enhance osteoblast differentiation of MSCs | Datta | []64 |
| Decellularized lung scaffolds for natural rodent lung | Natural rodents | CHAPS-based decellularization results in retention of elastin in the decellularized matrix, while SDS-based decellularization results in loss of elastin in the decellularized matrix | The 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 function | Petersen | []65 |
| Smooth muscle cells (SMCs) in 3-dimensional engineered tissues | The 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 scaffolds | 3-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 vitro | Kim | []67 | |
| Decellularized vascular stroma | After spinning the cell culture for 120 weeks, fibroblasts infiltrate approximately 40 μm into the elastin scaffold and approximately 4 μm into the collagen scaffold | Both scaffolds are completely decellular/they are highly biodegradable/fibroblasts adhere to the scaffold surface and proliferate, with excellent cell viability | Lu | []68 | |
| Rabbit conjunctival fibroblasts | Rabbit | Oriented scaffolds exhibit lower cell adhesion but higher cell proliferation due to the orientation of the fibers compared to random scaffolds | The arrangement of fibers can control cell orientation and enhance the interaction between cell bodies and fibers in the fiber longitudinal direction | Zhong | []69 |
| Binding microchannels that allow nutrient-rich medium to flow through collagen-based scaffolds | Transmission 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 carbonates | Appropriately sized microchannels within collagen-HA scaffolds bring us closer to meeting the mass transport requirements of osteoblasts living deep within the scaffold | Sachlos | []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 activity | This suggests that this composite has potential uses for bone tissue engineering | Hardy | []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. | |||||