The establishment of cartilage regenerative medicine is an important clinical issue, but the search for cell sources able to restore cartilage integrity proves to be challenging. Human mesenchymal stromal cells (MSCs) are prone to form epiphyseal or hypertrophic cartilage and have an age-related limited proliferation. On the other hand, it is difficult to obtain functional chondrocytes from human embryonic stem cells (ESCs). Moreover, the ethical issues associated with human ESCs are an additional disadvantage of using such cells. Since their discovery in 2006, induced pluripotent stems cells (iPSCs) have opened many gateways to regenerative medicine research, especially in cartilage tissue engineering therapies. iPSCs have the capacity to overcome limitations associated with current cell sources since large numbers of autologous cells can be derived from small starting populations. Moreover, problems associated with epiphyseal or hypertrophiccartilage formation can be overcome using iPSCs. iPSCs emerge as a promising cell source for treating cartilage defects and have the potential to be used in the clinical field. For this purpose, robust protocols to induce chondrogenesis, both in vitro an in vivo, are required. This review summarises the recent progress in iPSC technology and its applications for cartilage repair.
Knowledge and research results about hand osteoarthritis (hOA) are limited due to the lack of samples and animal models of the disease. Here, we report the generation of two induced pluripotent stem cell (iPSC)-lines from patients with radiographic hOA. Furthermore, we wondered whether these iPSC-lines carried single nucleotide polymorphisms (SNPs) within genes that have been associated with hOA. Finally, we performed chondrogenic differentiation of the iPSCs in order to prove their usefulness as cellular models of the disease. We performed a non-integrative reprogramming of dermal fibroblasts obtained from two patients with radiographic rhizarthrosis and non-erosive hOA by introducing the transcriptional factors Oct4, Sox2, Klf4 and c-Myc using Sendai virus. After reprogramming, embryonic stem cell-like colonies emerged in culture, which fulfilled all the criteria to be considered iPSCs. Both iPSC-lines carried variants associated with hOA in the four studied genes and showed differences in their chondrogenic capacity when compared with a healthy control iPSC-line. To our knowledge this is the first time that the generation of iPSC-lines from patients with rhizarthrosis and non-erosive hOA is reported. The obtained iPSC-lines might enable us to model the disease in vitro, and to deeper study both the molecular and cellular mechanisms underlying hOA. Osteoarthritis (OA) is a prevalent musculoskeletal disease that affects the joints, and it has a substantial effect on quality life 1-4. Hand OA affects predominantly the carpometacarpal joint (CMCJ), followed by the interphalangeal joints (IPJs), both proximal and distal 4. OA of the CMCJ, also known as rhizarthrosis or thumb OA, is the most common location in women over 55 years, and the severity is usually linked to handedness. Mechanical pain at the base of the thumb and the thenar eminence are the principal clinical manifestations of this pathology 5. Erosive hand OA is another form that may involve the CMCJ of the thumb as well as IPJs, in which central erosions are found in the subcondral bone 4. Although both the individual and the societal burden of hand OA are well known, knowledge and research results about its underlying cellular and molecular mechanisms are limited 3 , mainly due to the dearth of tissue samples and lack of animal models of this pathology 4,6. Cellular in vitro models are meaningful tools to shed light on the molecular mechanisms and pathways that are involved in hand OA. Primary chondrocytes, immortalized cell lines and mesenchymal stromal cells are commonly used as in vitro models of OA 6. However, they present
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