Vignon Christine, Hilpert Morgane, Toupet Karine, Goubaud Aurélien, Noël Danièle, de Kalbermatten Matthieu, Hénon Philippe, Jorgensen Christian, Barbero Andrea, Garitaonandia Ibon
CellProthera, Mulhouse, France.
Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Front Bioeng Biotechnol. 2023 May 23;11:1150522. doi: 10.3389/fbioe.2023.1150522. eCollection 2023.
Knee osteoarthritis (OA) is a degenerative joint disease of the knee that results from the progressive loss of articular cartilage. It is most common in the elderly and affects millions of people worldwide, leading to a continuous increase in the number of total knee replacement surgeries. These surgeries improve the patient's physical mobility, but can lead to late infection, loosening of the prosthesis, and persistent pain. We would like to investigate if cell-based therapies can avoid or delay such surgeries in patients with moderate OA by injecting expanded autologous peripheral blood derived CD34+ cells (ProtheraCytes) into the articular joint. In this study we evaluated the survival of ProtheraCytes when exposed to synovial fluid and their performance with a model consisting of their co-culture with human OA chondrocytes in separate layers of Transwells and with a murine model of OA. Here we show that ProtheraCytes maintain high viability (>95%) when exposed for up to 96 hours to synovial fluid from OA patients. Additionally, when co-cultured with OA chondrocytes, ProtheraCytes can modulate the expression of some chondrogenic (collagen II and Sox9) and inflammatory/degrading (IL1β, TNF, and MMP-13) markers at gene or protein levels. Finally, ProtheraCytes survive after injection into the knee of a collagenase-induced osteoarthritis mouse model, engrafting mainly in the synovial membrane, probably due to the fact that ProtheraCytes express CD44, a receptor of hyaluronic acid, which is abundantly present in the synovial membrane. This report provides preliminary evidence of the therapeutic potential of CD34+ cells on OA chondrocytes and their survival after implantation in the knee of mice and merits further investigation in future preclinical studies in OA models.
膝关节骨关节炎（OA）是一种膝关节退行性关节疾病，由关节软骨的逐渐丧失引起。它在老年人中最为常见，影响着全球数百万人，导致全膝关节置换手术的数量持续增加。这些手术可改善患者的身体活动能力，但可能导致晚期感染、假体松动和持续疼痛。我们想研究基于细胞的疗法是否可以通过将扩增的自体外周血来源的CD34+细胞（ProtheraCytes）注入关节，避免或延迟中度OA患者进行此类手术。在本研究中，我们评估了ProtheraCytes暴露于滑液时的存活率，以及在Transwells的不同层中与人类OA软骨细胞共培养的模型和OA小鼠模型中的表现。在这里，我们表明，当暴露于OA患者的滑液长达96小时时，ProtheraCytes保持高存活率（>95%）。此外，当与OA软骨细胞共培养时，ProtheraCytes可以在基因或蛋白质水平上调节一些软骨生成（胶原蛋白II和Sox9）以及炎症/降解（IL1β、TNF和MMP-13）标志物的表达。最后，ProtheraCytes注射到胶原酶诱导的骨关节炎小鼠模型的膝关节后能够存活，主要植入滑膜，这可能是因为ProtheraCytes表达CD44，一种透明质酸受体，而透明质酸在滑膜中大量存在。本报告提供了CD34+细胞对OA软骨细胞的治疗潜力及其植入小鼠膝关节后的存活情况的初步证据，值得在未来OA模型的临床前研究中进一步研究。
