Baek Seung-Hoon, Shim Bum-Jin, Won Heejae, Lee Sunray, Lee Yeon Kyung, Park Hyun Sook, Kim Shin-Yoon
Department of Orthopedic Surgery, Kyungpook National University Hospital, Daegu 41944, Republic of Korea.
Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Pharmaceuticals (Basel). 2024 Oct 13;17(10):1366. doi: 10.3390/ph17101366.
Although mesenchymal stem cells (MSCs) insertion has gained recent attention as a joint-preserving procedure, no study has conducted direct intralesional implantation of human umbilical cord-derived MSCs (hUCMSCs) in patients with ONFH. This is a protocol for a phase 1 clinical trial designed to assess the safety and exploratory efficacy of human umbilical cord-derived osteoblasts (hUC-Os), osteogenic differentiation-induced cells from hUCMSCs, in patients with early-stage ONFH. Nine patients with Association Research Circulation Osseous (ARCO) stage 1 or 2 will be assigned to a low-dose (1 × 10 hUC-O cells, = 3), medium-dose (2 × 10 cells, = 3), and high-dose group (4 × 10 cells, = 3) in the order of their arrival at the facility, and, depending on the occurrence of dose-limiting toxicity, up to 18 patients can be enrolled by applying the 3 + 3 escalation method. We will perform hUC-O (CF-M801) transplantation combined with core decompression and follow-up for 12 weeks according to the study protocol. Safety will be determined through adverse event assessment, laboratory tests including a panel reactive antibody test, vital sign assessment, physical examination, and electrocardiogram. Efficacy will be explored through the change in pain visual analog scale, Harris hip score, Western Ontario and McMaster Universities Osteoarthritis Index, ARCO stage, and also size and location of necrotic lesion according to Japanese Investigation Committee classification before and after the procedure. Joint preservation is important, particularly in younger, active patients with ONFH. Confirmation of the safety and efficacy of hUC-Os will lead to a further strategy to preserve joints for those suffering from ONFH and improve our current knowledge of cell therapy.
尽管间充质干细胞（MSCs）植入作为一种保关节手术最近受到了关注，但尚无研究对股骨头缺血性坏死（ONFH）患者进行人脐带间充质干细胞（hUCMSCs）的直接病灶内植入。这是一项1期临床试验方案，旨在评估人脐带来源的成骨细胞（hUC-Os，由hUCMSCs诱导成骨分化而来）对早期ONFH患者的安全性和探索性疗效。9例处于骨循环研究协会（ARCO）1期或2期的患者将按照到达研究机构的顺序被分配到低剂量组（1×10⁶ hUC-O细胞，n = 3）、中剂量组（2×10⁶细胞，n = 3）和高剂量组（4×10⁶细胞，n = 3），并且根据剂量限制性毒性的发生情况，采用3+3剂量递增法最多可纳入18例患者。我们将根据研究方案进行hUC-O（CF-M801）移植联合髓芯减压，并随访12周。通过不良事件评估、包括群体反应性抗体检测在内的实验室检查、生命体征评估、体格检查和心电图来确定安全性。通过疼痛视觉模拟量表、Harris髋关节评分、西安大略和麦克马斯特大学骨关节炎指数、ARCO分期的变化，以及根据日本调查委员会分类法评估手术前后坏死病灶的大小和位置来探索疗效。保关节很重要，尤其是对于年轻、活跃的ONFH患者。确认hUC-Os的安全性和疗效将为ONFH患者保关节带来进一步的策略，并增进我们目前对细胞治疗的认识。
