Stem cell-directed therapies for osteoarthritis: The promise and the practice

Abstract

Osteoarthritis (OA) is a disease of an entire synovial joint characterized by clinical symptoms and distortion of joint tissues, including cartilage, muscles, ligaments, and bone. Although OA is a disease of all joint tissues, it is a defined accessible compartment and is thus amenable to topical surgical and regenerative therapies, including stem cells. All tissues arise from stem progenitor cells, and the relative capacity of different cellular compartments, and different individuals, to renew tissues into adulthood may be important in the onset of many different degenerative diseases. OA is driven by both mechanical and inflammatory factors, but how these factors affect the proliferation and differentiation of cells into cartilage in vivo is largely unknown. Indeed, our very basic understanding of the physiological cellular kinetics and biology of the stem‐progenitor cell unit of the articular cartilage, and how this is influenced by mechano‐inflammatory injury, is largely unknown. OA seems, rather deceptively, to be the low‐hanging fruit for stem cell therapy. Without the basic understanding of the stem cell and progenitor unit that generate and maintain articular cartilage in vivo, we will continue to waste opportunities to both prevent and manage this disease. In this review, we discuss the biology of chondrogenesis, the stem cell populations that support articular cartilage in health and disease, and future opportunities afforded through the translation of basic articular chondrocyte stem cell biology into new clinical therapies.

Divergence in chondrogenic potential between in vitro and in vivo of adipose- and synovial-stem cells from mouse and human

“…Besides, we used subcutaneous fat from the knee area, which may have different characteristics from abdominal fat [56,57]. Recently, medical waste-derived stem cells such as adipose tissue, synovium, umbilical cord, and dental pulp have been highlighted for stem cell therapy because of low additional invasion for tissue collection and their superior proliferative capacity compared with BMSCs [11,58,59]. Our data are limited and may not be applicable to other cell types; therefore, further study is required using other sources.…”

In vivo cartilage-formation potency of somatic stem cells is associated with responsiveness to TGFβ stimulation in vitro

“…Besides, we used subcutaneous fat from the knee area, which may have different characteristics from abdominal fat [57,58]. Recently, medical waste-derived stem cells such as adipose tissue, synovium, umbilical cord, and dental pulp have been highlighted for stem cell therapy because of low additional invasion for tissue collection and their superior proliferative capacity compared with BMSCs [11,59,60]. Our data are limited and may not be applicable to other cell types; therefore, further study is required using other sources and cells puri ed from speci c populations.…”

Exosomes derived from mesenchymal stem cells inhibit catabolism in human chondrocytes by activating autophagy via inhibition of the NF-κB pathway

“…Exosomes are able to transfer cargos of nucleic acids (mRNAs and microRNAs), proteins, and bioactive lipids 18 . Exosomes can produce biological responses in recipient cells 28 . Some ndings have shown ambiguous effects of exosomes on the immune response or possible tumorigenicity, which may be considered unfavorable properties of exosomes 19,20 .…”

“…It is the end result of a combination of genetic, metabolic, biochemical, in ammatory, and mechanical predispositions and insults, but the loss of articular cartilage is certainly a consequence of this 27 . The loss of articular cartilage can, in turn, aggravate in ammation, joint misalignment, and bony remodeling (subchondral bone destruction and osteophyte development), loss of muscular and ligamentous joint support, and ultimately the de ning clinical symptoms of joint pain, instability and stiffness 28 . Chondrocytes are sensitive to physical injury, and extreme mechanical forces alter the chondrocyte balance of anabolic and catabolic factors, compounding injury and inducing in ammation 29 .…”