Tendon‐derived stem cells (TDSCs) promote tendon repair in a rat patellar tendon window defect model

Abstract

Injured tendons heal slowly and often result in the formation of mechanically and functionally inferior fibrotic scar tissue or fibrous adhesions. This study investigated the use of tendon-derived stem cells (TDSCs) for tendon repair in a rat patellar tendon window defect model. Fibrin glue constructs with or without GFP-TDSCs were transplanted into the window defect. The patellar tendons were harvested for histology, ex vivo fluorescent imaging and biomechanical test at various time points up to week 4. Our results showed that TDSCs significantly enhanced tendon healing as indicated by the increase in collagen production as shown by hematolxylin stain-ability of the tissue, improvement of cell alignment, collagen fiber alignment and collagen birefringence typical of tendon. The labeled cells were observed at weeks 1 and 2 and became almost undetectable at week 4. Both the ultimate stress and Young's modulus were significantly higher in the TDSCs group compared to those in the fibrin glue group at week 4. In conclusion, TDSCs promoted earlier and better repair in a rat patellar tendon window defect model.

Human iPSC-Derived Neural Crest Stem Cells Promote Tendon Repair in a Rat Patellar Tendon Window Defect Model

“…At scheduled time, the rats were sacrificed with an overdose of sodium pentobarbital for macroscopical observation, histology analysis, mechanical testing, and gene expression analysis. Previous studies 17,26 showed that biomechanical properties in the repaired tendon reach the peak at day 30 and plateau afterward in the tendon window defect model. In this study, therefore, we determined the effect of transplanted cells on tendon repair by structural and mechanical examinations, as well as the extracellular matrix (ECM) protein expression analysis at week 4.…”

“…Recently, the longstanding dogma that the mammalian tendon is a postmitotic organ with limited regenerative reserve had been challenged by the discovery of stem cells isolated from tendon. [14][15][16] Though tendon stem cells show healing promotion, [17][18][19][20] the application of tendon stem cells for tendon repair needs further investigation.…”

In Vivo Identity of Tendon Stem Cells and the Roles of Stem Cells in Tendon Healing

“…In Part II, a window wound of 1 mm in diameter was created in the patellar tendon of another 15 rats (weight: 150-200 g) at week 6 after IdU pulsing as previously described [21]. The intact patellar tendon in the contralateral limb of each rat served as a control.…”

“…The rats were anesthetized by an intramuscular injection of 10% ketamine/2% xylazine (Kethalar, 0.3 mL: 0.2 mL) and maintained sedation by 10% ketamine injected intravenously (Sigma Chemical CO, St. Louis, MO). To create the tendon defect, the central portion of the patellar tendon (*1 mm in width) was removed from the distal apex of the patella to the insertion of the tibia tuberosity without damaging the fibrocartilage zone with three stacked sharp blades as described in the previous study [21]. The wound was then closed in layers.…”

“…The co-localization of LRCs with CD44 and Sca-1, two commonly used in vitro MSC markers, in the midsubstance in intact tendon and at the window wound at day 7 after injury (see protocol below) was examined by coimmunofluorescent staining. Consecutive sections to the sections stained with CD146 and Sca-1 were stained with hematoxylin and eosin (H&E) for comparison.In Part II, a window wound of 1 mm in diameter was created in the patellar tendon of another 15 rats (weight: 150-200 g) at week 6 after IdU pulsing as previously described [21]. The intact patellar tendon in the contralateral limb of each rat served as a control.…”