15502-m-pleumeekers

INTRODUCTION Cartilage is a highly specialized avascular connective tissue located at a variety of anatomical locations such as the ear, nose, trachea, ribs and articular joints. In general, cartilage predominantly consists of an extracellular matrix (ECM), which is produced, maintained and remodeled by a relatively small amount of specialized cells (1-10%). [34] The exact composition of the ECM is mainly dependent on the tissue’s function and thus three major subtypes can be distinguished: hyaline, fibrous and elastic cartilage. It is well known that due to its avascular origin, cartilage itself has a limited self-regenerative capacity. As a result, cartilage deficits can lead to severe pain, disability and aesthetic impairment. Currently, surgical repair of cartilage requires either autogeneic cartilage grafts or artificial material implants. However, these conventional treatments are (1) associated with a limited availability of autogeneic tissue, (2) can cause donor site morbidity, and - in case of artificial implants - (3) are prone to generate a foreign body reaction. To overcome these problems, tissue engineering (TE) can offer a promising solution for restoring missing or damaged cartilage. TE-approaches have focused on the production of functional cartilage that has features similar to native tissue. In cartilage TE, small tissue biopsies are harvested, thus generating minimal donor site morbidity. Cells are isolated from the biopsies and stimulated to proliferate in culture providing large quantities of cells. These cells are subsequently stimulated to produce cartilage tissue which should structurally and morphologically resemble native tissue. One of the major challenges in cartilage TE is defining an appropriate cell source. The most obvious cell source is cartilage itself. Hyaline articular cartilage is most frequently used for cartilage TE, although some experiments have been published on the use of non-articular cartilages (e.g. nasal, ear and costal cartilage). [205] Next to chondrocytes, mesenchymal stem cells (MSCs) with their multi-lineage differentiation potential and easy availability from bone marrow or adipose tissue have been demonstrated as an attractive cell source for cartilage TE. [64, 66] To date, we and others have evaluated the use of chondrocytes and MSCs of several anatomical locations for their applicability in cartilage regenerative medicine. [39, 42-44, 46- 59, 206-209] However, precise comparison of the performance of culture-expanded human cells is lacking. This knowledge is important to be able to select an optimal cell source for each application of cartilage TE. The current study was designed to evaluate the performance of culture-expanded cells of several sources for generating a stable and functional ECM in vitro and in vivo . Therefore, human chondrocytes from ear, nose and articular joint and MSCs derived from bone marrow and adipose tissue were compared. Cartilage matrix production was evaluated using qRT-PCR and biochemical assays during in vitro culture. Biochemical assays, histology and mechanical tests were used to determine tissue stability and functionality of cartilage constructs after subsequent subcutaneous implantation in vivo . 61 CARTILAGE-FORMING CAPACITY OF SEVERAL CELL SOURCES 4