Department of Bioengineering, College of Engineering, and BK FOUR Biopharmaceutical Innovation Leader for Education and Research Group, Hanyang University, Seoul, Republic of Korea.
Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA, USA.
Nat Commun. 2024 Oct 23;15(1):9151. doi: 10.1038/s41467-024-53246-w.
In this study, we address the persistent challenge of providing adequate oxygen to transplanted cells by introducing a respiratoid biosystem. Central to our strategy is the chloroplast-transit-peptide (CTP), crucial for optimal oxygenation. Through conjugation of CTP with alginate, we achieve stabilization of chloroplast structure. Strategically anchored to the outer chloroplast membrane, CTP not only ensures structural integrity but also upregulates key photosynthesis-associated genes. This biosystem demonstrates exceptional efficacy in spontaneously generating oxygen, particularly under hypoxic conditions (~1% pO). In an application, pancreatic islets encapsulated within the respiratoid biosystem and intraperitoneally implanted in diabetic mice maintain normal glucose levels effectively. Insulin secretion persists for 100 days post-xenotransplantation without the need for immunosuppressant administration, highlighting the reliance on the respiratoid biosystem's oxygen supply and structural stability. Our study demonstrates the respiratoid biosystem as a platform in tissue engineering, offering a nature-inspired solution to the critical challenge of spontaneous oxygen supply.
在这项研究中，我们通过引入(respiratoid)生物系统来解决移植细胞供氧不足的难题。我们的策略核心是叶绿体转运肽（chloroplast-transit-peptide，CTP），它对于优化氧合至关重要。通过将 CTP 与藻酸盐结合，我们实现了叶绿体结构的稳定。叶绿体转运肽（CTP）被策略性地锚定在叶绿体外膜上，不仅确保了结构的完整性，还上调了关键的光合作用相关基因。该生物系统在自发产生氧气方面表现出了卓越的功效，特别是在缺氧条件下（~1% pO）。在一项应用中，封装在(respiratoid)生物系统中的胰岛被腹膜内植入糖尿病小鼠体内，有效地维持了正常的血糖水平。在异种移植后 100 天内，无需免疫抑制剂治疗即可持续分泌胰岛素，这凸显了对(respiratoid)生物系统供氧和结构稳定性的依赖。我们的研究表明，respiratoid 生物系统是组织工程中的一个平台，为自发供氧这一关键挑战提供了一种受自然启发的解决方案。
