Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

Abstract

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.

Cell Reprogramming Strategies for Treating Osteoarthritis and Intervertebral Disc Degeneration

“…However, as the main research method at present, animal models still face numerous challenges in translating to human pathology characterization [13]. In recent years, with the reported transformation of various somatic cells into chondrocytes and nucleus pulposus (NP) cells [14,15], iPSCs have made remarkable achievements in establishing disease models to explore disease pathological mechanisms, screen drugs, and treat diseases [16,17]. From the construction of preliminary OA models with typical pathological features from iPSCs, to the interpretation of OA-related genetic variation based on iPSCs' patientspecific characteristics and the evaluation and screen of drugs through the pathological changes of OA models [18][19][20].…”

Cell Therapy Approaches for Articular Cartilage Regeneration

“…A brief list of cell types, subtypes, sources and the advantages and disadvantages of each. Cell Types Cell Subtypes Sources Advantages Limitations Autologous Chondrocytes None Patient cartilage 53 No immunogenicity 29 Easeof procurement 29 Additional surgery 53 , 54 Costly 53 , 54 Complications regarding phenotype 16 , 55 Stem Cells Embryonic Stem Cells (ESCs) Human embryos 56 Pluripotency 57 Unlimitedcell source 58 Ethical concerns 55 , 59 Teratoma formation 56 immunogenicity 55 , 56 Induced Pluripotent Stem Cells (iPSCs) Blood 60 , 61 fibroblasts 56 Pluripotency 57 Unlimited cell source 55 , 58 No immunogenicity 57 …”

“… 100 Sources for iPSCs consist of the blood 60 , 61 and fibroblasts 68 in which isolated cells are lenti-virally altered to express common embryonic markers such as octamer-binding transcription factor 4 (Oct4), SRY-box 2 (Sox2), Kruppel-like factor 4 (Klf4), and c-myc. 55 Further analysis of iPSCs have allowed for the creation of the iPSC library. This “library” allows for the procurement of iPSCs from multiple donor types allowing for the creation of iPSCs from homozygous donors matching a specific HLA, reducing the potential for immune rejection.…”

“… 120 iPSCs can be applied to personalized medicine as they can be derived from the patient themselves limiting immune response. 55 However, understanding the complexities associated with iPSC differentiation into chondrocytes must be done prior to implementation in the clinical setting to avoid ethical concerns.…”

Skeletal muscle differentiation of human iPSCs meets bioengineering strategies: perspectives and challenges

“…With regard to skeletal muscle tissue engineering, there have been no interventional clinical trials using iPSC-derived muscle cells. To date, patient-derived iPSCs have mainly been used such as in vitro tools to model muscular diseases, to study the pathological molecular mechanisms, and for drug testing before in vivo translation 151 .…”