Review Article

The Functions and Mechanisms of Tendon Stem/Progenitor Cells in Tendon Healing

Table 2

Summary of results and characteristics of the studies which investigated the effects of TSPCs in tendon healing.

Animal typeModels establishDosageTime postoperationOutcomeConclusionReference

GFP-positive transgenic male ratsAchille tenotomy and repairGFP-TSC sheet2, 4 weeksRound shaped cells↑ cell numbers, ECM↑ Tnmd, and type I collagen↑ Ultimate Strength↑Better cellular alignment, elongation, and densely aligned collagen arrangement in the regenerated tissue at the TSC sheet grafted tendon defect area was observed[67]
Non-GFP SD male ratsPatellar tendon window injuryGFP-TDSC, CTGF ascorbic acid2, 4, 8, 16 weeksUltimate stress↑ collagen fibers↑ spindle-shaped cells↑ ectopic mineralized tissues↓The transplantation of TDSCs promoted tendon repair up to week 16[64]
Young adult horsesFlexor tendinitis induced by collagenaseTSPCs: 5 × 106 TSPCs in 0.15 ml of sterile phosphate-buffered saline1, 2, 4, 6, 12 weeksType I collagen, COMP, and tenomodulin mRNA↑ maximum stresses↑ collagen fibers were significantly more alignedTreatment of collagenase-induced flexor tendon injury with TSPCs not only improved the tensile strength of the repaired tissue, but also improved collagen fiber alignment[73]
SD male ratsWindow wound in the patellar tendon and repairNA3, 7, 14 days 4, 6, 8 weeksCD44+, Sca+↑ Scx, Tnmd, smad8↑ Oct4+, Nanog+, SOX2+, nucleostemin+ CD146↑The LRCs participated in tendon repair after injury via migration, proliferation, activation for tenogenesis, and increased pluripotency in the window wound[15]
SD ratsPatellar tendon window injuryGFP-TDSC fibrin1, 2, 4, 8, 16 weeksFiber arrangement ↑CD3, CD68 (1, 2 weeks) ↓CD163↓ Vascular distribution↓ transplanted cells↓Transplantation of allogeneic TSPCs to patellar tendon injury sites in rats not only promotes tendon healing, but also shows a weak immune response[53]
SD ratsPT transection and repairNA2 days 1, 2 weeksCD 146+TSC ↑TIMP-3↑ IL-10↑ IL-6↓CTGF delivery improves the quality of tendon healing by activating TSPCs. Similarly, TSPCs have an anti-inflammatory effect[16]
Female rabbitsRotator cuff tendon defectCell-seeded scaffold (knitted silk—collagen sponge + collagen gel containing allogenous rTSPCs)4, 8, 12 weeksCollagen I, collagen III, Bgn, and TNC ↑ fibroblastic cells↑ stiffness, maximum force, emerge, modulus, and stress at failure↑Allogenous TSPC-seeded scaffolds can promote healing of rotator cuff injury[49]
SD ratsAchilles tendon defectSeeded with TSPCs (ECM + TSPCs group, N = 12, 5 × 105 cells per scaffold)4 weeksOrganized collagen fiber structures↑ fibroblast-like cells↑ collagen type I ↑stiffness↑The tendon ECM scaffold inoculated with TSPCs not only promotes cell proliferation and stimulates collagen synthesis, but also improves the mechanical properties of the healing tendon[74]
Outbred non-GFP SD male ratsPatellar tendon Window injuryNA2, 4, 8 weeksmRNA expression of Scx ↑Swelling of the knee↓ degree of inflammation↓ fiber arrangement↑ ultimate stress↑ collagen type I↑GFP-TDSC-Scx group might promote early tendon repair by increasing the expression of collagen type I in the window wound[68]
Male outbred SD ratsACL excision and reconstructionGFP-TDSC sheet2, 6, 12 weeksCell alignment ↑collagen birefringence↑ ultimate load↑The TDSC sheet improved early graft healing after ACL reconstruction in the rat model[75]
SD ratsAchilles tendon rupture and repairCM (HGF + TSCs)2 weeksMMP-2, MMP-9↑ VEGF↑ Biomechanical properties↑CM treatment promotes repair and functional recovery of Achilles tendon ruptures[76]

Note: ↑, significant increase; ↓, significant decrease. NA, not applicable; TSPCs, human tendon stem/progenitor cells; Bgn, biglycan; CTGF, connective tissue growth factor; TNC, tenascin-C; COMP, cartilage oligomeric matrix protein; LRCs, label-retaining cells; Tnmd, tenomodulin; Scx, scleraxis; ECM, extracellular matrix; ACL, anterior cruciate ligament; MMP-2, matrix metallopeptidase 2; MMP-9, matrix metallopeptidase 2; VEGF, vascular endothelial growth factor, HGF, hepatocyte growth factor.