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Immunomodulatory Actions of Mesenchymal Stromal Cells (MSCs)
Cellular therapy offers regeneration which curbs osteoarthritis of the knee. Among cellular therapies, mesenchymal stromal cells (MSCs) are readily isolated from various sources as culture expanded and unexpanded cellular population which are used as therapeutic products. Though MSCs possess a unique immunological and regulatory profile through cross-talk between MSCs and immunoregulatory cells (T cells, NK cells, dendritic cells, B cells, neutrophils, monocytes, and macrophages), they provide an immunotolerant environment when transplanted to the site of action.
Osteoarthritis of the knee, also called degenerative arthritis or osteoarthrosis, is a multi-factorial, slowly progressing disease of the synovial joint . It is primarily a non-inflammatory degenerative disorder of the knee which is characterized by the progressive degenerative process leading to irreversible articular cartilage destruction . Among all musculoskeletal diseases, osteoarthritis of the knee poses significant health, economic and social burden to the aging population, hence it is prudent to exactly define and locate the etiological agent to contemplate an effective management strategy . A total of 15% of the world population is affected with osteoarthritis of the knee which leads to the major cause of activity limitation . Understanding the molecular and cellular components of the pathophysiology of osteoarthritis of the knee is of paramount importance to establish the cell-based therapy to formulate the disease-modifying strategy .
Osteoarthritis of the knee results due to degradation of the articular cartilage and the components of the bone matrix . The earliest pathomechanism in the progression of cartilage loss is due to the loss of type 2 collagen and aggrecans in the cartilage tissue . In the early stage of knee osteoarthritis, natural killer (NK) cells and macrophages play a significant role in pathogenesis and intervening these cross-talks pose a potential breakthrough in the management of osteoarthritis of the knee . Osteoarthritis of the knee is characterized by increased levels of pro-inflammatory cytokines such as IL-1 and TNF-α, raised expression of TGF-β, and the activation of matrix metalloproteinases (MMPs), ultimately leading to chondrocyte senescence .
Cytotherapy or cell-based therapies have been developed in the past decade for management of early knee osteoarthritis by utilizing the stem cells harvested from various donor tissues such as bone marrow, adipose tissue, placenta, synovium, dental tissues, peripheral blood, and rarely from embryonal tissues . In particular, mesenchymal stromal cell (MSC)-based cellular therapy demonstrate a promising tool for regenerating the degenerated cartilage in the osteoarthritic knee . A large number of published literature states that the regenerative capacity of MSCs is due to paracrine factors released by MSCs rather than the pluripotent nature of MSCs to differentiate into cells of the desired tissue . The ease of availability from multiple sources makes MSCs the versatile cell-based therapy of choice in regenerating tissues . Despite the promising results seen in vitro and in vivo studies, the application of MSCs are limited due to the risk of teratoma formation, limited viability of differentiated cells and rejection of the cells post transplantation .
There is no available evidence to prove that engrafted MSCs in osteoarthritis of the knee are differentiated into cartilage cells. These engrafted MSCs work in a paracrine fashion and stimulate the tissue-specific residual and resilient cells for tissue regeneration and repair . MSCs act by empowerment rather than replacement . The engrafted MSCs possess a stromal environment that contains both cellular and molecular components. 26 The combined action of cytokines and chemokines drive MSC to induce tissue regeneration by proliferation and differentiation of resident stem cells .
2. Immunomodulation by Living MSCs
3. Immunomodulation by Apoptotic MSCs
4. Cross-Talk between MSCs and Immunological Cells in Cartilage Regeneration
This entry is adapted from 10.3390/osteology1040020
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