Chung Seyong, Sung Hak-Joon
Department of Medical Engineering, Yonsei University College of Medicine, Seoul, Republic of Korea.
Pulse (Basel). 2024 May 29;12(1):58-65. doi: 10.1159/000538075. eCollection 2024 Jan-Dec.
Enhanced regenerative therapeutic strategies are required to treat intractable ischemic heart disease.
Since the discovery of putative endothelial progenitor cells (EPCs) in 1997, many studies have focused on their extraction, ex vivo processing, and autotransplantation under ischemic conditions. Nonetheless, numerous randomized clinical trials involving thousands of patients have yielded only marginal treatment effects, highlighting the need for advances regarding insufficient dosage and complex ex vivo processing. The prevailing paradigm of cellular differentiation highlights the potential of direct cellular reprogramming, which paves the way for in situ reprogramming. In situ reprogramming holds the promise of significantly enhancing current therapeutic strategies, yet its success hinges on the precise targeting of candidate cells for reprogramming. In this context, the spleen emerges as a pivotal "in situ reprogramming hub," owing to its dual function as both a principal site for nanoparticle distribution and a significant reservoir of putative EPCs. The in situ reprogramming of splenic EPCs offers a potential solution to overcome critical challenges, including the aforementioned insufficient dosage and complex ex vivo processing.
This review explores the latest advancements in EPC therapy and in situ reprogramming, spotlighting a pioneering study that integrates those two strategies with a specific focus on the spleen. Such an innovative approach will potentially herald a new era of regenerative therapy for ischemic heart disease.
治疗难治性缺血性心脏病需要增强再生治疗策略。
自1997年发现假定的内皮祖细胞（EPCs）以来，许多研究都集中在其提取、体外处理以及在缺血条件下的自体移植。尽管如此，涉及数千名患者的众多随机临床试验仅产生了微不足道的治疗效果，凸显了在剂量不足和复杂的体外处理方面取得进展的必要性。细胞分化的主流模式突出了直接细胞重编程的潜力，这为原位重编程铺平了道路。原位重编程有望显著增强当前的治疗策略，但其成功取决于对用于重编程的候选细胞的精确靶向。在这种背景下，脾脏成为一个关键的“原位重编程中心”，这是因为它兼具作为纳米颗粒分布的主要部位和假定EPCs的重要储存库的双重功能。脾脏EPCs的原位重编程为克服关键挑战提供了一种潜在解决方案，包括上述剂量不足和复杂的体外处理。
本综述探讨了EPC治疗和原位重编程的最新进展，重点介绍了一项开创性研究，该研究将这两种策略结合起来，特别关注脾脏。这种创新方法有望开创缺血性心脏病再生治疗的新时代。
