hiPSC-Derived M1 Macrophages Exhibit Synergistic Therapeutic Effects with Paclitaxel in Ovarian Cancer
hiPSC-Derived M1 Macrophages Exhibit Synergistic Therapeutic Effects with Paclitaxel in Ovarian Cancer
Jeong Suji(Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea); Cha Seho(KW Bio Co., Ltd, Chuncheon, Korea); Song Haengseok(Department of Biomedical Science, CHA University, Seongnam, Korea); Chang Heesoon(KW Bio Co., Ltd, Chuncheon, Korea); Na Sung Hun(Department of Obstetrics and Gynecology, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, Korea); Hong Seok Ho(Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, Korea); Park Mira(Department of Biomedical Informatics, Jeju National University, Jeju, Korea)
19권 1호, 93~101쪽
초록
Ovarian cancer remains one of the most lethal gynecologic malignancies, with limited responsiveness to standard chemotherapy and poor long-term prognosis. Tumor-associated macrophages, particularly M2-polarized populations, play a crucial role in immune suppression and tumor progression. Human induced pluripotent stem cells (hiPSCs) can differentiate into functional immune cells, providing an unlimited and patient-specific source for cell-based immunotherapy. In this study, we investigated the therapeutic potential of hiPSC-derived macrophages (hiMACs), specifically M1-polarized hiMACs, against ovarian cancer. In a co-culture system, M1-hiMACs significantly reduced the viability of ovarian cancer cells, inducing apoptosis and necrosis, whereas M0 macrophages showed minimal effects. In vivo, intravenous administration of M1-hiMACs into nude mice bearing ovarian cancer cells resulted in a dose-dependent reduction in tumor volume. Furthermore, combination therapy with paclitaxel and M1-hiMACs led to greater tumor regression and enhanced histological necrosis compared to either treatment alone. These findings demonstrate the potent anti-tumor effects of M1-hiMACs and highlight their potential for cellular immunotherapy for ovarian cancer, particularly in combination with chemotherapy.
Abstract
Ovarian cancer remains one of the most lethal gynecologic malignancies, with limited responsiveness to standard chemotherapy and poor long-term prognosis. Tumor-associated macrophages, particularly M2-polarized populations, play a crucial role in immune suppression and tumor progression. Human induced pluripotent stem cells (hiPSCs) can differentiate into functional immune cells, providing an unlimited and patient-specific source for cell-based immunotherapy. In this study, we investigated the therapeutic potential of hiPSC-derived macrophages (hiMACs), specifically M1-polarized hiMACs, against ovarian cancer. In a co-culture system, M1-hiMACs significantly reduced the viability of ovarian cancer cells, inducing apoptosis and necrosis, whereas M0 macrophages showed minimal effects. In vivo, intravenous administration of M1-hiMACs into nude mice bearing ovarian cancer cells resulted in a dose-dependent reduction in tumor volume. Furthermore, combination therapy with paclitaxel and M1-hiMACs led to greater tumor regression and enhanced histological necrosis compared to either treatment alone. These findings demonstrate the potent anti-tumor effects of M1-hiMACs and highlight their potential for cellular immunotherapy for ovarian cancer, particularly in combination with chemotherapy.
- 발행기관:
- 한국줄기세포학회
- 분류:
- 세포생물학