Rat Plantar Fascia Stem/Progenitor Cells Showed Lower Expression of Ligament Markers and Higher Pro-Inflammatory Cytokines after Intensive Mechanical Loading or Interleukin-1β Treatment In Vitro.

The pathogenesis of plantar fasciitis is unclear, which hampers the development of an effective treatment. The altered fate of plantar fascia stem/progenitor cells (PFSCs) under overuse-induced inflammation might contribute to the pathogenesis. This study aimed to isolate rat PFSCs and compared their stem cell-related properties with bone marrow stromal cells (BMSCs).

Bioactive Decellularized Tendon-Derived Stem Cell Sheet for Promoting Graft Healing After Anterior Cruciate Ligament Reconstruction.

Background: Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair.

Differential MMP 1 and MMP 13 expression in proliferation and ligamentization phases of graft remodeling in anterior cruciate ligament reconstruction.

: Graft remodeling in anterior cruciate ligament reconstruction (ACLR) demonstrates three distinct phases: necrosis, proliferation and ligamentization. Biological enhancement involves modulating these processes, but the cellular activities related to extracellular matrix remodeling have not been investigated. We hypothesized that changes in matrix metalloproteinases (MMPs) 1 and 13 expression are involved in the transition of proliferation phase to ligamentization phase of graft remodeling.

Effects of Redox Modulation on Cell Proliferation, Viability, and Migration in Cultured Rat and Human Tendon Progenitor Cells.

Tendon healing is slow and usually results in inferior fibrotic tissue formation. Recently, application of tendon derived stem cells (TDSCs) improved tendon healing in animal studies. In a chicken model, local injection of antioxidants reduced tendon adhesion after tendon injury.

Local administration of Trolox, a vitamin E analog, reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury.

Background: Hand flexor tendon injuries are compromised with tendon adhesion. Tendon adhesion forms between flexor tendon and tendon sheath, reduces the range of motion of fingers, and affects their function. Oxidative stress is increased in flexor tendon after injury and might play a role in tendon adhesion formation.

Transplantation of tendon-derived stem cells pre-treated with connective tissue growth factor and ascorbic acid in vitro promoted better tendon repair in a patellar tendon window injury rat model.

Background Aims: Treatment of tendon-derived stem cells (TDSCs) with connective tissue growth factor (CTGF) and ascorbic acid promoted their tenogenic differentiation. We investigated the effects of TDSCs pre-treated with CTGF and ascorbic acid on tendon repair in a patellar tendon window injury rat model.

Methods: Green fluorescent protein-TDSCs (GFP-TDSCs) were pre-treated with or without CTGF and ascorbic acid for 2 weeks before transplantation.

Peri-tunnel bone loss: does it affect early tendon graft to bone tunnel healing after ACL reconstruction?

Purpose: The clinical relevance and mechanisms of local bone loss early post-anterior cruciate ligament (ACL) reconstruction remain unclear. The early spatial and temporal changes of peri-tunnel bone, its molecular mechanisms and its relationships with graft-bone tunnel healing were investigated in a 12-week-old rat model.

Methods: At various times, the reconstructed ACL complex was harvested for vivaCT imaging, biomechanical test, histology and immunohistochemical staining of CD68+ cells (a monocyte-macrophage lineage marker), MMP1 and MMP13.

Scx-transduced tendon-derived stem cells (tdscs) promoted better tendon repair compared to mock-transduced cells in a rat patellar tendon window injury model.

We hypothesized that the transplantation of Scx-transduced tendon-derived stem cells (TDSCs) promoted better tendon repair compared to the transplantation of mock-transduced cells. This study thus aimed to investigate the effect of Scx transduction on the expression of lineage markers in TDSCs and the effect of the resulting cell line in the promotion of tendon repair. Rat non-GFP or GFP-TDSCs were transduced with Scx or empty lentiviral vector (Mock) and selected by blasticidin.

Immunogenicity and escape mechanisms of allogeneic tendon-derived stem cells.

The immunogenicity of tendon-derived stem cells (TDSCs) has implications for their clinical use for the promotion of tendon repair. The immunogenicity and escape mechanisms of rat patellar TDSCs were examined after allogeneic transplantation. Our results showed that TDSCs exhibited low immunogenicity as evidenced by the following: (i) the incubation of target TDSCs with immunized serum did not show antibody recognition and did not induce the complement-dependent cytotoxicity; (ii) target TDSCs elicited a very low level of lymphocyte proliferation and did not exhibit host lymphocyte-mediated cytotoxicity; and (iii) target TDSCs dose dependently suppressed the phorbol 12-myristate 13-acetate (PMA)- and ionomycin-induced host lymphocyte proliferation.

Allogeneic tendon-derived stem cells promote tendon healing and suppress immunoreactions in hosts: in vivo model.

The medium- to long-term healing effect and infiltration of inflammatory cells, after transplantation of allogeneic tendon-derived stem cell (TDSC) to the rat patellar tendon window wound, were examined. Allogeneic patellar TDSCs derived from a green fluorescent protein rat were used. The outcome of tendon healing and the infiltration of inflammatory cells were examined by histology and immunohistochemistry up to week 16 postinjury.

Application of tendon-derived stem cell sheet for the promotion of graft healing in anterior cruciate ligament reconstruction.

Background: Both osteointegration and remodeling of graft midsubstance (collectively called graft healing) are slow processes after anterior cruciate ligament (ACL) reconstruction. Tendon-derived stem cells (TDSCs) form a cell sheet after treatment with connective tissue growth factor (CTGF) and ascorbic acid, which exhibits higher tenogenic and maintains high chondro-osteogenic gene expression of TDSCs. No external scaffold is required for cell delivery.

Local administration of alendronate reduced peri-tunnel bone loss and promoted graft-bone tunnel healing with minimal systemic effect on bone in contralateral knee.

Continued systemic administration of alendronate was reported to reduce peri-tunnel bone resorption and promoted graft-bone tunnel healing at the early stage post-anterior cruciate ligament (ACL) reconstruction. However, systemic increase in bone mineral density (BMD) in the contralateral intact knee was observed. We tested if single local administration of alendronate into the bone tunnel during ACL reconstruction could achieve similar benefits yet without the systemic effect on bone.

In vivo identity of tendon stem cells and the roles of stem cells in tendon healing.

We investigated the spatial distribution of stem cells in tendons and the roles of stem cells in early tendon repair. The relationship between tendon-derived stem cells (TDSCs) isolated in vitro and tendon stem cells in vivo was also explored. Iododeoxyuridine (IdU) label-retaining method was used for labeling stem cells in rat patellar tendons with and without injury.

Expression of Wnt pathway mediators in metaplasic tissue in animal model and clinical samples of tendinopathy.

Objective: Tissue metaplasia is observed in both ossified failed healing animal model and clinical samples of tendinopathy. The Wnt signalling pathway plays a vital role in pathological calcification. We hypothesized that the Wnt signalling pathway might contribute to tissue metaplasia and failed healing in tendinopathy.

Local vitamin-C injection reduced tendon adhesion in a chicken model of flexor digitorum profundus tendon injury.

Background: Adhesion formation is a complication of hand flexor tendon repair. Normal gliding function of flexor tendons can be impaired by an excessive fibrotic response, which may be caused by intraoperative and postoperative hemorrhage. As tissue damage and hemorrhage can disturb redox regulation, thereby favoring fibrotic responses, the purpose of this study was to investigate if antioxidants can reduce tendon adhesion by antagonizing oxidative stress.

Validation of a histologic scoring system for the examination of quality of tendon graft to bone tunnel healing in anterior cruciate ligament reconstruction.

Objective: To develop and validate a histologic scoring system for the assessment of tendon graft to bone tunnel healing in anterior cruciate ligament (ACL) reconstruction.

Study Design: The scoring system, tendon-bone tunnel healing (TBTH) score, comprised 5 items on graft status,fiber type and interface connectivity, evaluated on either a 5- or 6-point scale. Two observers were trained to use the scoring system, examining 15 blinded histologic slides from an ongoing study.

Expression of chondro-osteogenic BMPs in clinical samples of patellar tendinopathy.

Purpose: The pathogenesis of patellar tendinopathy remains unclear. Expression of BMP-2/-4/-7 was reported in an ossified failed tendon healing animal model of patellar tendinopathy. This study aimed to investigate the expression of these chondro-osteogenic BMPs in clinical samples of patellar tendinopathy.

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

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.

Ectopic chondro-ossification and erroneous extracellular matrix deposition in a tendon window injury model.

The acquisition of chondro-osteogenic phenotypes and erroneous matrix deposition may account for poor tissue quality after acute tendon injury. We investigated the presence of chondrocyte phenotype, ossification, and the changes in the expression of major collagens and proteoglycans in the window wound in a rat patellar tendon window injury model using histology, von Kossa staining and immunohistochemistry of Sox 9, major collagens, and proteoglycans. Our results showed that the repair tissue did not restore to normal after acute injury.

Expression of chondro-osteogenic BMPs in ossified failed tendon healing model of tendinopathy.

Chondrocytes phenotype/markers were expressed in clinical samples of tendinopathy and calcifying tendinopathy. This study examined the spatial-temporal expression of chondro-osteogenic Bone Morphogenetic Proteins (BMPs), which might contribute to ectopic chondro-osteogenesis and failed healing process in tendinopathy. Collagenase was injected into patellar tendon of rats to induce ossified failed tendon healing.

Mechanical loading increased BMP-2 expression which promoted osteogenic differentiation of tendon-derived stem cells.

This study aimed to investigate the effect of repetitive tensile loading on the expression of BMP-2 and the effect of BMP-2 on the osteogenic differentiation of tendon-derived stem cells (TDSCs) in vitro. Repetitive stretching was applied to TDSCs isolated from rat patellar tendon at 0%, 4%, and 8%, 0.5 Hz.

Inferior tendon graft to bone tunnel healing at the tibia compared to that at the femur after anterior cruciate ligament reconstruction.

Background: Tunnel widening after anterior cruciate ligament (ACL) reconstruction (ACLR) is commonly reported without a clear understanding of the mechanism. This study aimed to quantify the spatiotemporal change of the newly formed bone mass, bone tunnel diameter, and area along both bone tunnels using micro-computed tomography (microCT) and correlated the result with histology.

Methods: ACLR was performed in 24 rabbits.

In vivo low-intensity pulsed ultrasound (LIPUS) following tendon injury promotes repair during granulation but suppresses decorin and biglycan expression during remodeling.

Study Design: Bench research, cross-sectional.

Objective: To determine if the effects of low-intensity pulsed ultrasound (LIPUS) on matrix synthesis change at different stages of tendon healing.

Background: LIPUS is effective in promoting tendon healing by stimulation of matrix synthesis.

Isolation and characterization of multipotent rat tendon-derived stem cells.

Stem cells have recently been isolated from humans and mice but not from rat tendon tissue. This study reports the isolation and characterization of stem cells from rat tendon. Nucleated cells isolated from rat flexor tendon tissues after collagenase digestion were plated at a low cell density to allow the selective proliferation of tendon-derived stem cells.

Sustained expression of proteoglycans and collagen type III/type I ratio in a calcified tendinopathy model.

Objectives: Alteration in the composition of extracellular matrix has been suggested as the major factor for the development of tendinopathy and calcified tendinopathy, which has poorer clinical manifestation. This study investigated the changes of major proteoglycans and collagens in a calcified tendinopathy model and correlated the expression with the acquisition of chondrocyte phenotype, ectopic ossification and loss of matrix organization in the same model.

Methods: Thirty-six rats were used.