Human Adipose- and Amnion-Derived Mesenchymal Stromal Cells Similarly Mitigate Osteoarthritis Progression in the Dunkin Hartley Guinea Pig

Abstract

Background: Clinical trials are currently underway to investigate the efficacy of intra-articular administration of mesenchymal stromal cells (MSCs) to mitigate osteoarthritis (OA) progression in the knee. Although multiple MSC sources exist, studies have yet to determine whether differences in therapeutic efficacy exist between them. Purpose: To compare the ability of intra-articularly injected adipose-derived MSCs (AD-MSCs) and amnion-derived MSCs (AM-MSCs) to mitigate the progression of knee OA in a small animal model of spontaneous OA, as well as to compare the therapeutic potential of MSCs in hyaluronic acid (HA) and in HA only with saline (OA) controls. Study Design: Controlled laboratory study. Methods: Injections of AD-MSCs or AM-MSCs suspended in HA or HA only were performed in the rear stifle joints of 3-month-old Dunkin Hartley guinea pigs (DHGPs). Repeat injections occurred at 2 and 4 months after the initial injection in each animal. Contralateral limbs received saline injections and served as untreated controls. Subsequently, joints were analyzed for osteoarthritic changes of the cartilage and subchondral bone via histologic and biochemical analyses. To evaluate MSC retention time in the joint space, DHGPs received a single intra-articular injection of fluorescently labeled AD-MSCs or AM-MSCs, and the fluorescence intensity was longitudinally tracked via an in vivo imaging system. Results: No statistically significant differences in outcomes were found when comparing the ability of AD-MSCs and AM-MSCs to mitigate OA. However, the injection of AD-MSCs, AM-MSCs, and HA-only treatments more effectively mitigated cartilage damage compared with that of saline controls by demonstrating higher amounts of cartilage glycosaminoglycan content and improved histological proteoglycan scoring while reducing the percentage of osteophytes present. Conclusion: Intra-articular injection of AD-MSCs, AM-MSCs, or HA only was able to similarly mitigate the progression of cartilage damage and reduce the percentage of osteophytes compared with that of saline controls in the DHGP. However, this study was unable to establish the superiority of AD-MSCs versus AM-MSCs as a treatment to mitigate spontaneous OA. Clinical Relevance: MSCs demonstrate the ability to mitigate the progression of knee OA and thus may be used in a prophylactic approach to delay the need for end-stage treatment strategies.

Protecting the regenerative environment: selecting the optimal delivery vehicle for cartilage repair—a narrative review

“…Small animal models of OA have the advantage of allowing larger sample size, less animal housing space requirement, and reduced cost versus larger animal models ( Mukherjee et al, 2022 ). Small animal models of OA include mouse, rat, guinea pig and rabbit ( Sato et al, 2012 ; Toghraie et al, 2012 ; ter Huurne et al, 2012 ; van Buul et al, 2014 ; Kim et al, 2014 ; Singh et al, 2014 ; Deng et al, 2015 ; Kuroda et al, 2015 ; Saulnier et al, 2015 ; Wang et al, 2015 ; Yang et al, 2015 ; Chiang et al, 2016 ; Hermeto et al, 2016 ; Latief et al, 2016 ; Li et al, 2016 ; Morille et al, 2016 ; Ozeki et al, 2016 ; Mei et al, 2017a ; Mei et al, 2017b ; Parrilli et al, 2017 ; Chang et al, 2018 ; Choi et al, 2018 ; Desando et al, 2018 ; Fan et al, 2018 ; Neybecker et al, 2018 ; Cheng et al, 2019 ; Desando et al, 2019 ; Mahmoud et al, 2019 ; McKinney et al, 2019 ; Vinod et al, 2019 ; Zhou et al, 2019 ; Jeon et al, 2020 ; Tong et al, 2020 ; Wang et al, 2020 ; Xing et al, 2020 ; Zhi et al, 2020 ; Tang et al, 2021 ; Xing et al, 2021 ; Juskovic et al, 2022 ; Kwapisz et al, 2022 ; Wang et al, 2023 ) ( Table 2 ). Techniques to initiate OA include anterior cruciate transection (ACLT), ACLT with destabilization of the medial meniscus (DMM), chemically- (e.g., Mono-iodoacetate [MIA] or papain intraarticular injection) or collagenase-induced, as well as spontaneous OA ( Culley et al, 2015 ).…”

“…In order to treat the entire articular surface, investigators have largely relied on fluid-based vehicles to deliver their regenerative biological elements, including saline/PBS, serum, and media ( Toghraie et al, 2012 ; ter Huurne et al, 2012 ; van Buul et al, 2014 ; Singh et al, 2014 ; Saulnier et al, 2015 ; Yang et al, 2015 ; Latief et al, 2016 ; Li et al, 2016 ; Ozeki et al, 2016 ; Mei et al, 2017b ; Chang et al, 2018 ; Choi et al, 2018 ; Fan et al, 2018 ; Neybecker et al, 2018 ; Cheng et al, 2019 ; Desando et al, 2019 ; Mahmoud et al, 2019 ; Zhou et al, 2019 ; Jeon et al, 2020 ; Tong et al, 2020 ; Zhi et al, 2020 ; Tang et al, 2021 ; Xing et al, 2021 ; Juskovic et al, 2022 ; Wang et al, 2023 ) ( Table 2 ; Figure 1 ). More recently, HA has become commonly used ( Sato et al, 2012 ; Deng et al, 2015 ; Kuroda et al, 2015 ; Wang et al, 2015 ; Chiang et al, 2016 ; Vinod et al, 2019 ; Wang et al, 2020 ; Xing et al, 2020 ; Kwapisz et al, 2022 ). As well, semi-permeable microspheres, such as Poly (D,L-lactide-co-glycolide)-poloxamer P188-poly (D,L-lactideco-glycolide) polymer microspheres ( Morille et al, 2016 ) and sodium alginate microspheres ( McKinney et al, 2019 ), have been used to encapsulate bone marrow-derived MSCs.…”