Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Center of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.
Department of Thyroid, Sichuan Second Hospital of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Front Immunol. 2024 Apr 17;15:1385022. doi: 10.3389/fimmu.2024.1385022. eCollection 2024.
Liver failure represents a critical medical condition with a traditionally grim prognosis, where treatment options have been notably limited. Historically, liver transplantation has stood as the sole definitive cure, yet the stark disparity between the limited availability of liver donations and the high demand for such organs has significantly hampered its feasibility. This discrepancy has necessitated the exploration of hepatocyte transplantation as a temporary, supportive intervention. In light of this, our review delves into the burgeoning field of hepatocyte transplantation, with a focus on the latest advancements in maintaining hepatocyte function, co-microencapsulation techniques, xenogeneic hepatocyte transplantation, and the selection of materials for microencapsulation. Our examination of hepatocyte microencapsulation research highlights that, to date, most studies have been conducted or using liver failure mouse models, with a notable paucity of experiments on larger mammals. The functionality of microencapsulated hepatocytes is primarily inferred through indirect measures such as urea and albumin production and the rate of ammonia clearance. Furthermore, research on the mechanisms underlying hepatocyte co-microencapsulation remains limited, and the practicality of xenogeneic hepatocyte transplantation requires further validation. The potential of hepatocyte microencapsulation extends beyond the current scope of application, suggesting a promising horizon for liver failure treatment modalities. Innovations in encapsulation materials and techniques aim to enhance cell viability and function, indicating a need for comprehensive studies that bridge the gap between small-scale laboratory success and clinical applicability. Moreover, the integration of bioengineering and regenerative medicine offers novel pathways to refine hepatocyte transplantation, potentially overcoming the challenges of immune rejection and ensuring the long-term functionality of transplanted cells. In conclusion, while hepatocyte microencapsulation and transplantation herald a new era in liver failure therapy, significant strides must be made to translate these experimental approaches into viable clinical solutions. Future research should aim to expand the experimental models to include larger mammals, thereby providing a clearer understanding of the clinical potential of these therapies. Additionally, a deeper exploration into the mechanisms of cell survival and function within microcapsules, alongside the development of innovative encapsulation materials, will be critical in advancing the field and offering new hope to patients with liver failure.
肝脏衰竭是一种严重的医疗状况,传统上预后不佳,治疗选择非常有限。历史上,肝移植是唯一的根治方法,但由于可供移植的肝脏数量有限,而对这些器官的需求却很高,这使得肝移植的可行性受到了严重限制。这种差异促使人们探索肝细胞移植作为一种临时的支持性干预措施。有鉴于此,我们的综述深入探讨了肝细胞移植这一日益发展的领域,重点介绍了维持肝细胞功能、共微囊化技术、异种肝细胞移植以及微囊化材料选择方面的最新进展。我们对肝细胞微囊化研究的考察表明,迄今为止,大多数研究都是在肝衰竭小鼠模型上进行的,而在较大型哺乳动物上进行的实验则明显较少。微囊化肝细胞的功能主要通过间接测量来推断,如尿素和白蛋白的产生以及氨清除率。此外,肝细胞共微囊化的机制研究仍然有限,异种肝细胞移植的实用性还需要进一步验证。肝细胞微囊化的潜力超出了当前的应用范围,为肝脏衰竭治疗方法提供了广阔的前景。封装材料和技术的创新旨在提高细胞的活力和功能,这表明需要进行全面的研究,以弥合小规模实验室成功与临床应用之间的差距。此外,生物工程和再生医学的结合为改进肝细胞移植提供了新的途径,有可能克服免疫排斥的挑战,确保移植细胞的长期功能。总之,尽管肝细胞微囊化和移植为肝脏衰竭治疗带来了新的时代,但要将这些实验方法转化为可行的临床解决方案,还需要做出重大努力。未来的研究应旨在将实验模型扩展到包括较大型哺乳动物,从而更清楚地了解这些疗法的临床潜力。此外,深入探讨细胞在微囊中存活和发挥功能的机制,以及开发创新的封装材料,对于推动该领域的发展和为肝脏衰竭患者带来新的希望至关重要。