Abstract
The infrapatellar fat pad (IFP) has until recently been viewed as a densely vascular and innervated intracapsular/extrasynovial tissue with biomechanical roles in the anterior compartment of the knee. Over the last decade, secondary to the proposition that the IFP and synovium function as a single unit, its recognized tight molecular crosstalk with emerging roles in the pathophysiology of joint disease, and the characterization of immune-related resident cells with varying phenotypes (e.g., pro and anti-inflammatory macrophages), this structural complex has gained increasing attention as a potential therapeutic target in patients with various knee pathologies including osteoarthritis (KOA). Furthermore, the description of the presence of mesenchymal stem/stromal cells (MSC) as perivascular cells within the IFP (IFP-MSC), exhibiting immunomodulatory, anti-fibrotic and neutralizing activities over key local mediators, has promoted the IFP as an alternative source of MSC for cell-based therapy protocols. These complementary concepts have supported the growing notion of immune and inflammatory events participating in the pathogenesis of KOA, with the IFP/synovium complex engaging not only in amplifying local pathological responses, but also as a reservoir of potential therapeutic cell-based products. Consequently, the aim of this review is to outline the latest discoveries related with the IFP/synovium complex as both an active participant during KOA initiation and progression thus emerging as a potential target, and a source of therapeutic IFP-MSCs. Finally, we discuss how these notions may help the design of novel treatments for KOA through modulation of local cellular and molecular cascades that ultimately lead to joint destruction.
Highlights
The infrapatellar fat pad (IFP), known as Hoffa’s fat pad, is a cylinder-like piece of adipose tissue that sits posterior to the patella and fills the anterior knee compartment (Dragoo et al, 2012)
This collective peripheral sensory nociceptive innervation pattern is mediated by nerve fibers equipped with the neurotransmitter Substance P which runs separately but in parallel to sympathetic fibers and it is implicated in knee pain transmission
The knowledge accrued over the last decade regarding the IFP has led to important discoveries that elucidate its role beyond that of a vascular tissue with a biomechanical role in the anterior compartment of the knee
Summary
The infrapatellar fat pad (IFP), known as Hoffa’s fat pad, is a cylinder-like piece of adipose tissue that sits posterior to the patella and fills the anterior knee compartment (Dragoo et al, 2012). Because of its relatively newfound MSC population, current literature has re-focused on updating the knowledge of IFP anatomy, function, and most importantly its cellular composition beyond MSC This has led to extensive investment in the IFP’s potential for regenerative medicine in Orthopedics, and the role the IFP may play in certain pathological processes including KOA. Previous studies have confirmed that posterior articular branches from the tibial, saphenous, recurrent peroneal, and common peroneal nerve provide most of the innervation, Gardner et al recently described branches arising from the saphenous and obturator nerves as well (Freeman and Wyke, 1967; Kennedy et al, 1982) This collective peripheral sensory nociceptive innervation pattern (dense in parts of the IFP and synovium) is mediated by nerve fibers equipped with the neurotransmitter Substance P which runs separately but in parallel to sympathetic fibers and it is implicated in knee pain transmission. Within the IFP tyrosine hydroxylase (TH)-positive sympathetic fibers modulate nociception/pain signaling in sympathetic neurons, through interacting with Substance P-positive fibers (Dragoo et al, 2012; Brumovsky, 2016)
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