Baafi Kelvin, March John C
Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, 14853, USA.
Biotechnol Notes. 2022 Dec 9;4:7-13. doi: 10.1016/j.biotno.2022.11.005. eCollection 2023.
Reprogrammed glucose-responsive, insulin + cells ("-like") exhibit the potential to bypass the hurdles of exogenous insulin delivery in treating diabetes mellitus. Current cell-based therapies-transcription factor regulation, biomolecule-mediated enteric signaling, and transgenics - have demonstrated the promise of reprogramming either mature or progenitor gut cells into surrogate "-like" cells. However, there are predominant challenges impeding the use of gut "-like" cells as clinical replacements for insulin therapy. Reprogrammed "-like" gut cells, even those of enteroendocrine origin, mostly do not exhibit glucose - potentiated insulin secretion. Despite the exceptionally low conversion rate of gut cells into surrogate "-like" cells, the therapeutic quantity of gut "-like" cells needed for normoglycemia has not even been established. There is also a lingering uncertainty regarding the functionality and bioavailability of gut derived insulin. Herein, we review the strategies, challenges, and opportunities in the generation of functional, reprogrammed "-like" cells.
重编程的葡萄糖反应性胰岛素+细胞（“类”细胞）在治疗糖尿病方面展现出绕过外源性胰岛素递送障碍的潜力。当前基于细胞的疗法——转录因子调控、生物分子介导的肠道信号传导和转基因技术——已证明将成熟或祖细胞肠道细胞重编程为替代“类”细胞的前景。然而，存在一些主要挑战阻碍了将肠道“类”细胞用作胰岛素治疗的临床替代物。重编程的“类”肠道细胞，即使是肠内分泌起源的细胞，大多也不表现出葡萄糖增强的胰岛素分泌。尽管肠道细胞向替代“类”细胞的转化率极低，但正常血糖所需的肠道“类”细胞治疗量甚至尚未确定。关于肠道来源胰岛素的功能和生物利用度也一直存在不确定性。在此，我们综述了生成功能性重编程“类”细胞的策略、挑战和机遇。
