Treatment of Spontaneous Osteoarthritis with Micro-fragmented Adipose Tissue Graft in Dog

Osteoarthritis (syn: OA, degenerative joint disease, osteoarthritis) can be defined as a disease of the movable joints [1] characterized by chronic deterioration of the articu- lar cartilage with altered subchondral bone metabolism, the formation of periarticular osteophytes, a degree variable synovial inflammation leading to progressive joint stiffness and pain [2]. It is the most common form of arthritis in dogs and cats and also reported in human species as common as well [3]. In 2005, 26.9 million adults in the USA were estimated to have OA [4], up from 21 million in 1990. As reported from the Osteoarthritis Research Society International (OARSI) the osteoarthritis accounts for 2.4% of all years lived with disabilities (YLD) and has been ranked as the 10th leading contributor to global YLDs [5]. In Veterinary Medicine, although robust epidemiological data are lacking, it has been estimated that approximately 20% of adult dogs are affected by OA [6] and also re- ported as well in more than 60% of adult cats which showed radiographic evidence of this condition in the appendicular skeleton [7]. Pet dogs share both an environ- ment and lifestyle with their owners, and a growing public awareness is developing and also among researchers of the One Health Medicine. Dog's OA is generally con- sidered to bear a close resemblance to human OA, which regards anatomic similarity, disease heterogeneity and progression [8]. For this reason, several human researchers used dogs with spontaneous OA and ranks this species as the best animal model adopted for research [9]. Furthermore, mutual co-studies on osteoarthritis in veterina- ry and human medicine could be beneficial in both humans and dogs itself. One Health Medicine is emerging as a holistic paradigm wherein veterinary and human medical researchers and clinical practitioners collaborate to increase their understan- ding of shared diseases and to develop new therapies [10]. OA is not a single disease, and is often misperceived as a disease of only cartilage, but it is a complex degenerative joint disease which have to be controlled with a mul- timodal therapies [11]. Multimodal management of canine osteoarthritis is based on several therapeutic approach including non-steroidal anti-inflammatory medications (NSAIDs), joint supplements, weight management, and rehabilitation therapy [6;12]. When common conservative therapies fail to provide a long-term response, and a surgical management is not the proper decision to make, regenerative medicine is another option in the multimodal approach to manage OA [13]. Several publication reports the use of different interarticular regenerative medications in dogs affected by OA, such as hyaluronic acid, non transfusional hemocomponent (PRP, PRF, IRAP) mesenchiamal stem cells, and stromall vascular fraction. [13-15] In the last few years, medical researchers on the Regenerative field focus on the the- rapeutic properties of the mesenchymal stem cells (MSCs) to know the feasibility and the efficacy of their use [16-17]. Although mesenchymal stem cells were originally isolated from bone marrow [18-19], similar populations have been reported in other tissues. Human MSC have been isolated from adipose tissue [20], umbilical cord blood [21–24], peripheral blood [25-26], connective tissues of the dermis, and skeletal muscle [27]. Due to the characteristic high concentration of stem cells, the simple isolation, and the plastic properties, the scientific community shows a particular interest in MSCs derived from adipose tissue, which is called Adipose-Derived Stem Cells [28-31]. The adipose tissue once processed, allow to extract the aqueous fraction consisting of ASCs and the stromal vascular fraction (SVF). SVF contains precursors of endothe- lial cells (EPCs), macrophages, smooth muscle cells, lymphocytes, pericytes, pre- adipocytes [32]. The clinical efficacy in the treatment of OA through SVF infiltration is linked to its anti-inflammatory and immunoregulatory effects, alongside the rege- nerative capacity of ASCs [28]. Mesenchymal stem cells (MSCs) are considered to be a promising candidate for cartilage regeneration, due to their ability to differentia- te towards cartilage and bone cells and secrete trophic factors with regenerative func- tions [33]. The paracrine effect and anti-apoptotic, anti-inflammatory and anti-aging functions of these stem cells, is fundamental for the regeneration process. ASCs are a positive alternative treatment for OA, as in vitro studies have proven they contain CD73, CD90, CD105, and CD106 markers, which are necessary for cell differentia- tion into cartilage, moreover, in vivo studies have also reported good results, despite with some limits yet [34-35]. Over the past decade, research has brought new insights into the effects of ASCs, and more new mechanical disintegration technologies promise to achieve rapid, ready-to- use stem cell collection.[36-38]. The following research aims to validate a novel system for the disintegration of adi- pose tissue in dogs and evaluate the effectiveness of intra-articular injection of mi- cro-fragmented adipose tissue (MFAT) for the treatment of spontaneous osteoarthritis in dogs by comparing the use of hyaluronic acid, currently considered standard of care for the treatment of OA.