Abstract

Simple SummaryMesenchymal stem cells are located in bone marrow, adipose tissue, synovial membrane, and muscular tissue. They have an immunosuppressive, anti-inflammatory, and antifibrotic effect. Tissue engineering considers the usage of mesenchymal stem cells as a possible option for regenerating tissues, with respect to bone and cartilage, due to their ability to differentiate into multiple cytotypes (including chondrocytes and osteoblasts). Herein, we characterize a non-invasive solution based on Rigenera® technology, a mechanical disaggregation method able to produce autologous adipose tissue-derived micrografts which are analogous to adipose-derived stem cells.Within the adult canine population, disabilities and symptoms including joint pain and functional impairment are commonly observed in articular cartilage lesions and present a challenging feat in the operating room. Clinical settings require less invasive and more minimally manipulated measures facilitated by innovative and advanced technology. Mesenchymal stem cells have recently been proposed and, furthermore, autologous adipose tissue administration via injection has emerged as a new albeit somewhat controversial therapeutic tool. The purpose of this study is to characterize canine autologous micro-fragmented adipose tissue (micrografts) by mechanical approach without substantial manipulations. Adipose tissue samples collected from six dogs were processed by a Rigenera device and by enzymatic digestion from two different body regions (lumbar and thigh region). Interestingly, the immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, less positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies (which play a role in immune responses). Finally, the Rigenera® technology obtained micrografts with a 35% higher expression of the IL10 gene with relevant anti-inflammatory activities compared to the enzymatic digestion protocol. This evidence suggests a potential improved clinical outcome capable of modulating inflammation and immune responses.

Highlights

  • Osteoarthrosis (OA) is a common degenerative, chronic, inflammatory, painful, and disabling condition which affects the joints

  • The aim of this work is to characterize the stromal vascular fraction” (SVF) obtained by a well-known commercial system (Rigenera® ) through mechanical disruption of canine adipose tissue without substantial manipulations

  • The immunophenotypic analysis attested that cells from Rigenera® were highly positive for the mesenchymal stem cells markers CD73 and CD90, low positive for hematopoietic CD45 and CD34, and negative for MHC class II antibodies, playing a role in immune responses

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Summary

Introduction

Osteoarthrosis (OA) is a common degenerative, chronic, inflammatory, painful, and disabling condition which affects the joints. OA is one of the most disabling diseases in dogs [5,6,7,8,9] and is characterized by lameness, chronic pain, and functional impairment with a reduced quality of life. Treatment of OA aims mainly to reduce pain and inflammation through drug administration, appropriate diets, and physiotherapeutic sessions. The non-operative approach is the most common. When this fails, surgical treatment can be performed [11,12,13,14,15]. OA is still today the main cause of non-traumatic euthanasia in dogs since pharmacological drugs (FANS/FAS) mitigate articular pain without affecting OA progression. Scientific research has focused on substances able to slow down the progression of OA, regenerating the damaged tissues through local delivery instead of oral or parenteral drug administration, to avoid systematic side effects

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