Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 1879837, 17 pages http://dx.doi.org/10.1155/2016/1879837 Review Article Applications of Chondrocyte-Based Cartilage Engineering: An Overview Abdul-Rehman Phull,1 Seong-Hui Eo,1 Qamar Abbas,1 Madiha Ahmed,2 and Song Ja Kim1 1 Department of Biological Sciences, College of Natural Sciences, Kongju National University, Gongjudaehakro 56, Gongju 32588, Republic of Korea 2Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan Correspondence should be addressed to Song Ja Kim; [email protected] Received 14 May 2016; Revised 24 June 2016; Accepted 26 June 2016 Academic Editor: Magali Cucchiarini Copyright © 2016 Abdul-Rehman Phull et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chondrocytes are the exclusive cells residing in cartilage and maintain the functionality of cartilage tissue. Series of biocomponents such as different growth factors, cytokines, and transcriptional factors regulate the mesenchymal stem cells (MSCs) differentiation to chondrocytes. The number of chondrocytes and dedifferentiation are the key limitations in subsequent clinical application of the chondrocytes. Different culture methods are being developed to overcome such issues. Using tissue engineering and cell based approaches, chondrocytes offer prominent therapeutic option specifically in orthopedics for cartilage repair and to treat ailments such as tracheal defects, facial reconstruction, and urinary incontinence. Matrix-assisted autologous chondrocyte transplantation/implantation is an improved version of traditional autologous chondrocyte transplantation (ACT) method. An increasing number of studies show the clinical significance of this technique for the chondral lesions treatment. Literature survey was carried out to address clinical and functional findings by using various ACT procedures. The current study was conducted to study the pharmacological significance andiomedical b application of chondrocytes. Furthermore, it is inferred from the present study that long term follow-up studies are required to evaluate the potential of these methods and specific positive outcomes. 1. Introduction Cellular condensation is the initial marker of differentia- tion which occurs during chondrogenesis and the formation The chondrocytes are the only cells found in cartilage. These of skeletal elements. Mesenchymal stem cells (MSCs) are are unique in their secluded nature, having no direct access the multipotent cells arising from lateral plate mesoderm, to the vascular system. The chondrocytes are providing cranial neural crest, and somites. Most of the molecular mechanical support as a key functional component and per- events involved in the differentiation of the MSCs towards mit smooth pain-free articulation in cartilage. Chondrocytes chondrocytes are yet to be explored. Committed progen- demonstrate distinctive features such as being metabolically itor cell sequentially differentiated as chondroprogenitor active to maintain the turnover of extracellular matrix (ECM) cell, chondroblasts, chondrocytes, and finally hypertrophic by synthesising glycoprotein, collagens, proteoglycans, and chondrocytes. Sequential events of differentiation are shown hyaluronan. Chondrocytes have higher matrix to cell volume in Figure 1, while a number of signalling components are occupying10%oftissuevolumeandcanbecorrelatedwith required for the inductions of chondrogenesis which have functional feature of mammalian articular cartilages [1]. been identified and further understanding of downstream Protein and gene expression, metabolic activity, and surface regulation is in progress. Here we summarize the factors markers are common sharing features of the chondrocytes which act as commencing agents in chondrogenesis. The Sox9 and differences can be observed along the depth of the transcription factor is the key regulator of chondrogenesis, cartilage tissues. Various studies described the chondrocytes which is expressed during condensation of mesenchymal as mechanocyte, capable of responding to the mechanical progenitor cells and results in the generation of spheri- signalsinconnectivetissuelineage[2]. cal immature chondrocytes containing cartilage primordial 2 BioMed Research International Factors Cells Mesenchymal stem cells (MSCs) BMP-2, BMP-4, BMP-7 FGF-2, Wnt-3a TGF- a BMP-2, BMP-4, BMP-7 FGF-2, IGF- Marrow Ligamentogenesis/ Osteogenesis Myogenesis Chondrogenesis stroma tendogenesis BMP-2, BMP-7 b FGF-9, FGF-18 TGF- Chondrocyte Osteocytes Stromal cells Myotube Fibroblast VEGF, BMP-2, -catanin, FGF-2, TGF-, Wint-4, Wint-8 c Ligament/ Cartilage Bone Marrow Muscle tendon ECM proteins a Fibronectin, N-cadherin, tenascin, Col I, Col IIa b Aggrecan, Col IX, COMP, Col IIb, CD-RAP c AP, MMP-13, Col X Figure 1: Mesenchymal stem cells (MSCs) differentiations towards chondrocytes and other cell types. Differentiation and growth factors profile are schematically represented in sequence. Characteristic extracellular matrix (ECM) proteins at different stages are presented. Col, collagen; COMP, cartilage oligomeric protein; CD-RAP, cartilage-derived retinoic acid-sensitive protein; AP, alkaline phosphatase; MMP, matrix metalloprotease; BMPs, bone morphogenetic proteins; FGF, fibroblast growth factor; Wnt, Wingless Factors; TGF, transforming growth factor; IGF, insulin-like growth factor; VEGF, vascular endothelial growth factor. [3]. Chondrocytes within cartilage primordial continue to interactions. Chondrocytes undergo phenotypic variation express Sox9 and then undergo maturation. About twentyfold depending on the conditions of the growth environment. increase in volume of the cells takes place in this process [4] Therefore, these cells show loss in phenotype state when and resultant cells are called hypertrophic chondrocytes. growninmonolayercultures.Thevariationsintheshapeare Usually mature chondrocytes are round or polygonal the consequence of the several signalling pathways, matrix- with flattened edges in their structure but also found to specific components formation, and gene expression. Addi- have discoid or flattened shape (Figure 1). The chondrocyte tionally, compressive load modifies the cellular expression cells are normally found in lacunae (matrix cavities) and through mechanotransduction phenomenon [1]. Location establishing 5–10% of cartilage volume. These cells are about and origin determine the fate of chondrocytes. The cell in 13 mm diameter, playing a fundamental role in the mainte- epiphyseal growth plates leads to hypertrophy and terminal nance of the ECM stabilization [5]. The mature chondrocytes differentiation assists in ossification of endochondral tis- have the abundant Golgi apparatus and rough endoplasmic sues. Hypertrophic chondrocytes in calcified cartilaginous reticulum and possess prominent nucleus. Under higher matrix facilitate the bone setting on it. In this perspective, magnification human chondrocytes appeared to have oval chondrocytes undergo apoptotic cell death or metaplasia or or round nucleoli and a pair of centrioles in a juxtanuclear transdifferentiate to osteoblast resulting in the conversion cell centre in electron micrograph. Further, occasional lipid of the cartilage to bone [7]. Factors involved in the fate of droplets, elongated mitochondria, enlarged Golgi region, chondrocytes are yet to be interpreted. and basophilic cytoplasm are found in regenerating carti- Chondrocytes are low proliferative in their nature, having lage or new forming matrix [6]. The pericellular matrix is vitalroleinhomeostasisbyregulatingandproducingECM present around these cells and chondrocytes lack cell-to-cell components. The primary function of the chondrocytes is to BioMed Research International 3 provide structural support to articular, nasal, and tracheal of chondrocytes and is to speculate on the biomedical cartilagethatisrequiredintissuefunctionsandwithstands importance of these cells in different fields. physical deformation. The chondrocytes play dynamic role The articular cartilage pathology may be driven by cy- in growth epiphyseal plate through involvement of differ- tokines, growth factors, variations in biomechanics, and cel- entmechanismssuchasanincreaseinmatrixsecretions, lular responses [13]. Autologous chondrocyte transplanta- cell volume during terminal differentiation (hypertrophy), tion (ACT), abrasive chondroplasty, microdrilling/micro- and proliferation of the cells. These mechanisms contribute fracturing, and osteochondral grafting are extensively exe- to growth but may vary between joints, growth period, cuted procedures by the orthopedic surgeons for the artic- and also epiphyseal growth plate as supporting diaphysis ular cartilage repair. Among other experimental approaches, andepiphysis.Duetotheabsenceofthevascularsystem tissue engineering is promising option for the structural and in articular cartilage, chondrocytes rely on the diffusion functional reconstruction of the cartilage tissues. Cells such for metabolite exchange to get nourishment. Chondrocytes as chondrocytes, signalling molecules, and matrix scaffold metabolismusuallytakesplaceintherangeof>1–10% oxygen are the three fundamental constituents of such an approach tension depending on the location of the cell. Therefore, [14]. Development of regenerative cartilage medicine has most of the energy is