مقالات پذیرفته شده در ششمین کنگره بین المللی زیست پزشکی
A Review on Osteoarthritis and Stem Cell Therapy
A Review on Osteoarthritis and Stem Cell Therapy
Yasaman Dalman,1,*Nazanin Khaki,2
1. Biomateials Department, Biomedcial Engineering Faculty, Amirkabir University of Technology, Tehran, Iran. 2. Biomateials Department, Biomedcial Engineering Faculty, Amirkabir University of Technology, Tehran, Iran.
Introduction: Osteoarthritis (OA) is a leading cause of disability worldwide and disease of an entire synovial joint characterized by clinical symptoms and distortion of joint tissues including cartilage, muscles, bones, menisci, and ligaments. Articular cartilage exhibits little or no ability for self-repair, resulting in progressive tissue loss and dysfunction following isolated cartilage injuries. The lack of effective repair also contributes to the widespread degeneration of the joint associated with OA. There are both intrinsic joint and extrinsic environmental risk factors for OA. It is often linked to age, gender, menopause, genetics, nutrition, and bone density that increases one's susceptibility to OA. These systemic factors, in addition to mechanical factors such as weight/body mass index, injury, repeated stress on the joint, surgery, and bone deformation play a role in OA severity. There is currently no cure for OA and most treatments are essentially symptomatic therapies to manage pain, stiffness, and swelling that are largely unsatisfactory. Currently, based on OA stages, there are different approaches. Pharmacologic management includes acetaminophen, aspirin, oral non-steroidal anti-inflammatory drugs (NSAIDs) and intra-articular corticosteroid injections. Aside from patient education, strengthening exercises, and weight loss, these drugs are recommended in a secondary manner. It has also been shown that physical and occupational therapy can be beneficial. Despite their efficacy for early management, these conservative treatments have little impact on underlying structural abnormalities. In addition, total joint replacement as a treatment for patients with end‐stage OA is so invasive. Stem cells have extraordinary potential to contribute to novel treatment strategies for OA in different stages.
Methods: In this study, the method of a library collection, search in various texts, and authoritative scientific articles have been used.
Results: There are two regenerative therapeutic strategies for cartilage defects and osteoarthritis. Exogenous cell-based therapy entails delivery of autologous or allogeneic cells such as chondrocytes or mesenchymal stromal/stem cells (MSCs), or extracellular vesicles (EVs), either in suspension or seeded in a biomaterial. Alternatively, endogenous chondro progenitors, which reside in synovium (S), bone marrow (BM) and cartilage itself, could be targeted with pharmaceutical drugs or bioactive scaffolds to trigger or enhance intrinsic repair. Among these approches, MSCs have been successfully isolated from several adult tissues including the bone marrow, adipose tissue, synovium, and peripheral blood. The wide use of MSCs in clinical trials is largely attributed to their ex vivo expansion capacity, easy accessibility and isolation from several adult tissues. The MSCs mechanism in joints is not clear and there are some hypotheses. Despite disappearing quickly from the target tissue after administration, MSCs are still able to exert chondroprotective and immunomodulatory effects. Since their therapeutic efficacy seems to be independent of their engraftment, it is now considered to be mainly paracrine mediated. The increasingly accepted model is that MSCs are found dormant in vivo as pericytes. These participate in the development of tissues, including synovium, and are involved in tissue repair during adult life. Once activated in response to signals associated with the injured environment, such as pro-inflammatory cytokines, a phenomenon generally referred to as “licensing,” they secrete factors, including chemokines and cytokines, to establish a regenerative environment. Proposed mechanism of action for tissue repair by endogenous MSCs are anti-apoptotic, anti-catabolic, anti-fibrotic, pro-chondrogenic, pro-angiogenic and immune-modulatory.
The development of stem cell-based therapies for osteoarthritis also faces a number of challenges, such as the effects of age or disease on stem cell properties, altered stem cell function due to an inflammatory joint environment, and phenotypic instability in vivo that should be considered.
Conclusion: The development of stem cell-based therapies for OA is at a critical juncture. As a result of the extensive literature on stem cells, chondrogenic differentiation, and scaffold design, researchers and clinicians have been able to consider stem cells as a possible tool for modifying osteoarthritis progression. By using tissue engineering, osteoarthritic joints can be resurfaced to prevent or delay joint replacement and reduce the need for total joint replacements. There are, however, critical challenges specific to OA that threaten to obstruct the successful implementation of stem cell therapies. Therefore, it is clear that further studies are needed.