Combining canine mesenchymal stromal cells and hyaluronic acid for cartilage repair

Abstract

Cell therapy and tissue engineering have been intensively researched for repair of articular cartilage. In this study, we investigated the chondrogenic potential of canine adipose-derived mesenchymal stromal cells (ASCs) combined to high molecular weight hyaluronic acid (HA) in vitro, and their therapeutic effect in dogs with chronic osteoarthritis (OA) associated with bilateral hip dysplasia. Canine ASCs were characterized after conventional 2D culture or 3D culture in HA, showing adequate immunophenotype, proliferation and trilineage differentiation, as well as chondrogenesis after cultivation in HA. ASC/HA constructs were used to treat 12 dogs with OA, sequentially assigned to control, ASC and ASC/HA groups. Animals were examined for clinical, orthopedic and radiological parameters. Lameness at walk and pain on manipulation were reduced in the ASC group and mainly in the ASC/HA group. Range of motion and detection of crepitus on hip rotation and abduction improved similarly in all groups. For articular edema, muscle atrophy, Norberg angle values and radiographic analyses, there were no variations throughout the period. These results indicate that ASC/HA constructs are safe and may be an effective therapeutic tool in treating canine chronic osteoarthritis, which should be confirmed with larger studies and additional clinical parameters.

Review: Mesenchymal Stem Cell Therapy in Canine Osteoarthritis Research: “Experientia Docet” (Experience Will Teach Us)

“…None of the studies on autologous and allogeneic MSC in dogs with naturally-occurring OA involving radiographic and CT imaging did show improvement of superficial bone changes 3 -12 months post-treatment (36,41,42,49,60). Nevertheless, throughout the study period, no radiographic OA progression was detected after IA application of autologous and allogeneic adipose tissue-derived MSCs (41,49).…”

“…To apply autologous, allogeneic or xenogeneic MSCs as a therapeutic tool, cells need to be harvested from tissue and cultured in laboratory conditions. In canine OA research, the use of a variety of MSC sources is described, such as adipose tissue (28,32,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51), bone marrow (52)(53)(54)(55)(56)(57)(58), synovium (59), dental pulp (60), fetal adnexa (61), umbilical cord (62,63) and peripheral blood (31). Currently, adipose tissue and bone marrow seem to be the most popular MSC sources.…”

“…Current canine OA research on auto-, allo-, and xenotransplantation of MSCs, can be subdivided into two study types (based on the study population) (Figure 1). The first type and majority of canine OA studies include companion animals suffering from naturally-occurring OA (Tables 1, 2, 3) (28,31,32,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(60)(61)(62). In studies of a second type, joint damage is induced in purpose-bred dogs in order to investigate the potential of MSCs to heal cartilage (Tables 4, 5) (51)(52)(53)(54)(55)(56)(57)(58)(59)63).…”

“…Studies evaluating naturally-occurring OA have an advantage over model-based studies since they evaluate the effect of MSCs on a real world (field) condition (28,31,32,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(60)(61)(62). Nevertheless, establishing natural OA studies often encounters some difficulties.…”

“…The types of lacking analyses differed greatly between studies, but in general cell morphology and proliferation were the least evaluated MSC characteristics. An analyzation of the cell surface markers was described most commonly (28,32,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(60)(61)(62). Daems et al (31), who investigated the use of xenogeneic MSCs in dogs with naturally occurring OA, presented the most complete set of MSC characterizing analyses (31).…”