The Potency of Induced Pluripotent Stem Cells in Cartilage Regeneration and Osteoarthritis Treatment

Abstract

Osteoarthritis (OA) is the most common chronic disabling condition effecting the elderly, significantly impacting an individual patient's quality of life. Current treatment options for OA are focused on pain management and slowing degradation of cartilage. Some modern surgical techniques aimed at encouraging regeneration at defect sites have met with limited long-term success. Mesenchymal stem cells (MSCs) have been viewed recently as a potential tool in OA repair due to their chondrogenic capacity. Several studies have shown success with regards to reducing patient's OA-related pain and discomfort but have been less successful in inducing chondrocyte regeneration. The heterogeneity of MSCs and their limited proliferation capacity also raises issues when developing an off-the-shelf treatment for OA. Induced pluripotent stem cell (iPSC) technology, which allows for the easy production of cells capable of prolonged self-renewal and producing any somatic cell type, may overcome those limitations. Patient derived iPSCs can also be used to gain new insight into heredity-related OA. Efforts to generate chondrocytes from iPSCs through embryoid bodies or mesenchymal intermediate stages have struggled to produce with optimal functional characteristics. However, iPSCs potential to produce cells for future OA therapies has been supported by iPSC-derived teratomas, which have shown an ability to produce functional, stable articular cartilage. Other iPSCs-chondrogenic protocols are also improving by incorporating tissue engineering techniques to better mimic developmental conditions.

iPSCs in Modeling and Therapy of Osteoarthritis

“…Since OA is a systemic pathologic condition and a complex disease affected by several factors (genetic and environmental), it is challenging to generate an in vitro model [ 27 ]. The pathology of OA does not involve only the articular cartilage defects, but the whole joint including perichondrium, menisci, bone, synovial membrane, ligaments, and muscle.…”

Over-Production of Therapeutic Growth Factors for Articular Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines

“…A detailed discussion of cell and stem cell therapy for OA is beyond the scope of this review. The readers are referred to a series of excellent research and review articles that cover this topic [ 104 , 105 ] including several comprehensive reviews from our own group [ 106 ] that discuss the potential for using primary chondrocytes [ 107 ] adipose, bone marrow, and synovial mesenchymal stromal cells (MSCs) [ 108 , 109 , 110 ], menstrual blood-derived stem cells [ 111 ], and induced pluripotent stem cells (iPSCs) [ 112 ]. The most important point to make is that MSCs derived from patients with advanced OA exhibit attenuated chondrogenic activity, suggesting that these cells may be poor candidates for cell-based therapies for OA [ 113 ].…”

Over-Production of Therapeutic Growth Factors for Cartilage Regeneration by Protein Production Platforms and Protein Packaging Cell Lines: A Narrative Review of the Current State-of-the-Art

“…The readers are referred to a series of excellent research and review articles that cover this topic [42,43] including several comprehensive reviews from our own group [44] that discuss the potential for using primary chondrocytes [45] adipose, bone marrow and synovial mesenchymal stromal cells (MSCs) [46][47][48], menstrual blood-derived stem cells [49] and induced pluripotent stem cells (iPSCs) [50]. The most important point to make is that MSCs derived from patients with advanced OA exhibit attenuated chondrogenic activity, suggesting that these cells may be poor candidates for cell-based therapies for OA [51].…”