Low-dose xenogeneic mesenchymal stem cells target canine osteoarthritis through systemic immunomodulation and homing.

"Declarations Ethics approval and consent to participateThis efficacy study (approval number EC: 2019_003), the biodistribution study (approval number EC: 2019_007), and the blood collection of the donor horses (approval number: EC_2018_002) were approved by an independent ethics committee approved by the Flemish government (recognition number: LA1700607). In addition, the Klifovet Animal Welfare Body evaluated the efficacy study and its procedures according to Directive 2010/63/EU (Klifovet Reg.-No: 18-08), concluding that the study could be conducted as planned. Both clinical studies were compliant with good clinical practices (VICH GL9), and all animal handlings were conducted according to European, national and regional animal welfare regulations (Directive 2001/82/EC as amended, Belgian animal welfare legislation (KB 29/05/2013), Directive 2010/63/EU, and EMEA/CVMP/816/00-Final), and the principle of the 3Rs was applied. An informed consent was obtained for all study participants. Consent for publicationNot applicable. Competing interestsThe authors declare that this study was sponsored by Boehringer Ingelheim Veterinary Medicine Belgium (BIVMB) NV. The sponsor had the following involvement with the study: study design, data collection and analysis, decision to publish and preparation of the manuscript. CB, SB, ED, GP, LT, LVH and JHS are all employed by Boehringer Ingelheim or an affiliated company. JHS is an inventor of a pending patent covering the described immunomodulating technology owned by BIVMB (EP19162270.3). EDP, CB and JHS are the inventors of a patent covering the 99mTc labelling of ePB-MSCs owned by BIVMB (EP19200152.7). JHS, SB, GPA and CB are inventors of pending patent covering the mesenchymal stem cells for use in the treatment of osteoarthritis in animals owned by BIVMB (EP21184474.1). The content of this manuscript contains a stem cell product under development owned by BIVMB. GB and KH are employed by Klifovet AG. ND is the owner of a private veterinarian referral practice ‘De Molenkreek’. NV, TD are employed by Anacura. Other authors have no conflict of interest to declare. Competing interests The authors declare that this study was sponsored by Boehringer Ingelheim Veterinary Medicine Belgium (BIVMB) NV. The sponsor had the following involvement with the study: study design, data collection and analysis, decision to publish and preparation of the manuscript. CB, SB, ED, GP, LT, LVH and JHS are all employed by Boehringer Ingelheim or an affiliated company. JHS is an inventor of a pending patent covering the described immunomodulating technology owned by BIVMB (EP19162270.3). EDP, CB and JHS are the inventors of a patent covering the 99mTc labelling of ePB-MSCs owned by BIVMB (EP19200152.7). JHS, SB, GPA and CB are inventors of pending patent covering the mesenchymal stem cells for use in the treatment of osteoarthritis in animals owned by BIVMB (EP21184474.1). The content of this manuscript contains a stem cell product under development owned by BIVMB. GB and KH are employed by Klifovet AG. ND is the owner of a private veterinarian referral practice ‘De Molenkreek’. NV, TD are employed by Anacura. Other authors have no conflict of interest to declare."

"Funding The authors declare that this study received funding from Boehringer Ingelheim Veterinary Medicine Belgium NV. The funder had the following involvement with the study: study design, data collection and analysis, decision to publish, and preparation of the manuscript. This study was supported by a grant (HBC.2019.2343) from the Flemish Agency for Innovation and Entrepreneurship (Vlaio)."