Extracellular vesicles from cartilage progenitors stimulate type II collagen expression and wound healing in meniscal cells.

Knee meniscus tearing is a common orthopaedic injury that can heal poorly if left untreated, increasing the risk of post-traumatic Osteoarthritis. Intraarticular injection of human cartilage-derived progenitor cells (CPCs) has been shown to promote meniscus healing after injury. However, the mechanism by which CPCs stimulated this effect was unclear.

Kartogenin Induces Chondrogenesis in Cartilage Progenitor Cells and Attenuates Cell Hypertrophy in Marrow-Derived Stromal Cells.

Introduction: Kartogenin (KGN) is a synthetic small molecule that stimulates chondrogenic cellular differentiation by activating smad-4/5 pathways. KGN has been proposed as a feasible alternative to expensive biologic growth factors, such as transforming growth factor β, which remain under strict regulatory scrutiny when it comes to use in patients.

Method: This study reports the previously unexplored effects of KGN stimulation on cartilage- derived mesenchymal progenitor cells (CPCs), which have been shown to be effective in applications of cell-based musculoskeletal tissue regeneration.

Post-Traumatic Osteoarthritis Assessment in Emerging and Advanced Pre-Clinical Meniscus Repair Strategies: A Review.

Surgical repair of meniscus injury is intended to help alleviate pain, prevent further exacerbation of the injury, restore normal knee function, and inhibit the accelerated development of post-traumatic osteoarthritis (PTOA). Meniscus injuries that are treated poorly or left untreated are reported to significantly increase the risk of PTOA in patients. Current surgical approaches for the treatment of meniscus injuries do not eliminate the risk of accelerated PTOA development.

Implementation of Endogenous and Exogenous Mesenchymal Progenitor Cells for Skeletal Tissue Regeneration and Repair.

Harnessing adult mesenchymal stem/progenitor cells to stimulate skeletal tissue repair is a strategy that is being actively investigated. While scientists continue to develop creative and thoughtful ways to utilize these cells for tissue repair, the vast majority of these methodologies can ultimately be categorized into two main approaches: (1) Facilitating the recruitment of endogenous host cells to the injury site; and (2) physically administering into the injury site cells themselves, exogenously, either by autologous or allogeneic implantation. The aim of this paper is to comprehensively review recent key literature on the use of these two approaches in stimulating healing and repair of different skeletal tissues.

Distal-Less Homeobox 5 Is a Therapeutic Target for Attenuating Hypertrophy and Apoptosis of Mesenchymal Progenitor Cells.

Chondrocyte hypertrophy is a hallmark of osteoarthritis (OA) pathology. In the present study, we elucidated the mechanism underlying the relationship between the hypertrophy/apoptotic phenotype and OA pathogenesis in bone marrow-derived mesenchymal stem cells (BM-MSCs) via gene targeting of distal-less homeobox 5 (DLX5). Our primary objectives were (1) to determine whether DLX5 is a predictive biomarker of cellular hypertrophy in human osteoarthritic tissues; (2) To determine whether modulating DLX5 activity can regulate cell hypertrophy in mesenchymal stem/progenitor cells from marrow and cartilage.

SDF-1 preconditioned HPC scaffolds mobilize cartilage-derived progenitors and stimulate meniscal fibrocartilage repair in human explant tissue culture.

: The purpose of this study was to characterize the influence of SDF-1 on cell migration/adhesion and temporal gene expression of human cartilage mesenchymal progenitor cells (C-PCs); and to utilize SDF-1 conditioned mesenchymal progenitors to stimulate reintegration of human meniscus fibrocartilage breaks.: Characterization of SDF-1-induced cell migration was achieved using hydroxypropyl cellulose (HPC) scaffolds pretreated with SDF-1. Fluorescence microscopy and cell counting were used to visualize and quantify the extent of cell migration into scaffolds, respectively.

Aggrecan is required for chondrocyte differentiation in ATDC5 chondroprogenitor cells.

Aggrecan is an integral component of the extracellular matrix in cartilaginous tissues, including the growth plate. Heterozygous defects in the aggrecan gene have been identified as a cause of autosomal dominant short stature, bone age acceleration, and premature growth cessation. The mechanisms accounting for this phenotype remain unknown.

Human Cartilage-Derived Progenitors Resist Terminal Differentiation and Require CXCR4 Activation to Successfully Bridge Meniscus Tissue Tears.

Meniscus injuries are among the most common orthopedic injuries. Tears in the inner one-third of the meniscus heal poorly and present a significant clinical challenge. In this study, we hypothesized that progenitor cells from healthy human articular cartilage (chondroprogenitor cells [C-PCs]) may be more suitable than bone-marrow mesenchymal stem cells (BM-MSCs) to mediate bridging and reintegration of fibrocartilage tissue tears in meniscus.