Wang Long-Hai, Ernst Alexander Ulrich, Flanders James Arthur, Liu Wanjun, Wang Xi, Datta Ashim K, Epel Boris, Kotecha Mrignayani, Papas Klearchos K, Ma Minglin
Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853, USA.
Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.
Sci Adv. 2021 May 14;7(20). doi: 10.1126/sciadv.abd5835. Print 2021 May.
Cell encapsulation represents a promising therapeutic strategy for many hormone-deficient diseases such as type 1 diabetes (T1D). However, adequate oxygenation of the encapsulated cells remains a challenge, especially in the poorly oxygenated subcutaneous site. Here, we present an encapsulation system that generates oxygen (O) for the cells from their own waste product, carbon dioxide (CO), in a self-regulated (i.e., "inverse breathing") way. We leveraged a gas-solid (CO-lithium peroxide) reaction that was completely separated from the aqueous cellular environment by a gas permeable membrane. O measurements and imaging validated CO-responsive O release, which improved cell survival in hypoxic conditions. Simulation-guided optimization yielded a device that restored normoglycemia of immunocompetent diabetic mice for over 3 months. Furthermore, functional islets were observed in scaled-up device implants in minipigs retrieved after 2 months. This inverse breathing device provides a potential system to support long-term cell function in the clinically attractive subcutaneous site.
细胞封装是治疗许多激素缺乏性疾病（如1型糖尿病，T1D）的一种很有前景的治疗策略。然而，如何使封装的细胞获得充足的氧气仍然是一个挑战，尤其是在皮下低氧部位。在此，我们展示了一种封装系统，该系统能以自我调节（即“逆呼吸”）的方式，利用细胞自身的废物二氧化碳（CO₂）为细胞产生氧气（O₂）。我们利用了一种气固（CO₂-过氧化锂）反应，该反应通过透气膜与细胞的水性环境完全分隔开。氧气测量和成像验证了CO₂响应性氧气释放，这提高了低氧条件下细胞的存活率。模拟引导的优化产生了一种装置，该装置能使具有免疫活性的糖尿病小鼠的血糖恢复正常超过3个月。此外，在2个月后取出的小型猪的放大装置植入物中观察到了功能性胰岛。这种逆呼吸装置为在临床上有吸引力的皮下部位支持细胞长期功能提供了一个潜在的系统。
