Dekompense Sirozu Olan Hastalar İçin Otolog CLiP Hücre Nakli Protokolü Faz I/II Çalışması

Özet (abstract)

Introduction Decompensated cirrhosis is associated with a poor prognosis and limited therapeutic options for patients who are not candidates for liver transplantation. Although various cell-based regenerative therapies have been investigated, their clinical benefits are limited. Autologous chemically-induced liver progenitor cells (CLiPs) are expandable progenitor-like cells generated from mature hepatocytes using small-molecule reprogramming and have demonstrated regenerative potential in multiple preclinical models. Because CLiPs are bipotent and can differentiate toward both hepatocytic and biliary epithelial lineages, their lineage fate after transplantation may be influenced by the recipient liver microenvironment, and whether transplanted CLiPs undergo hepatocytic maturation in the human decompensated cirrhotic liver to the extent observed in animal models remains unknown. We describe the rationale and design of the first-in-human clinical trial evaluating autologous CLiP transplantation for decompensated cirrhosis. Setting Autologous CLiP cells (CLP-001) are manufactured from liver tissue obtained by laparoscopic partial hepatectomy and expanded in a certified Cell Processing Center under controlled conditions. Quality and safety assessment includes histopathological examination of the harvested liver tissue, sterility, endotoxin and mycoplasma testing, viable cell count, cell viability, cell-surface marker characterization, copy-number variation (CNV) analysis, and targeted cancer-related gene-panel testing (Table 1). The study is conducted under the Japanese Act on the Safety of Regenerative Medicine and has been approved by a Certified Special Committee for Regenerative Medicine. Methods This is a first-in-human, single-center, open-label, single-arm phase I/II study. Three adults with Child–Pugh class B decompensated cirrhosis who are not candidates for liver transplantation will be enrolled. Approximately 30 g of liver tissue will be harvested laparoscopically and used for CLiP manufacturing over a 12–16 week period. Following successful quality and safety testing, CLP-001 will be administered into the portal venous system through surgical cannulation of the ileocolic vein. The primary endpoint is safety, defined as adverse events and product-related deficiencies from tissue procurement through 1 month after transplantation. Secondary and exploratory endpoints include safety through 12 months and descriptive changes in liver function, fibrosis-related biomarkers, liver stiffness, and clinical manifestations of cirrhosis. Conclusion This is, to our knowledge, the first clinical evaluation of autologous CLiP transplantation in patients with decompensated cirrhosis. The trial is designed to establish the safety and procedural feasibility of the entire therapeutic workflow, including tissue procurement, cell manufacturing, quality assurance, and portal venous administration. Efficacy-related observations are exploratory, and the lineage fate of transplanted CLiPs cannot be directly established in this study. The findings are expected to provide the first clinical evidence regarding the safety and feasibility of autologous CLiP transplantation and support the future development of CLiP-based regenerative therapy for advanced chronic liver disease. At the time of submission, patient enrollment has commenced, and no participant has yet undergone CLiP transplantation.

Yazarların özeti; kaynağından alınmıştır. Regenerative Therapy, 2026 · DOI ↗