Cell and Molecular Therapy Center (NUCEL), School of Medicine, University of São Paulo, São Paulo, SP, 05360-130, Brazil.
Department of Biochemistry, Chemistry Institute, University of São Paulo, São Paulo, SP, 05508-000, Brazil.
Stem Cell Res Ther. 2022 Jul 15;13(1):309. doi: 10.1186/s13287-022-02977-y.
Type 1 diabetes mellitus (T1D) is a chronic disease characterized by an autoimmune destruction of insulin-producing β-pancreatic cells. Although many advances have been achieved in T1D treatment, current therapy strategies are often unable to maintain perfect control of glycemic levels. Several studies are searching for new and improved methodologies for expansion of β-cell cultures in vitro to increase the supply of these cells for pancreatic islets replacement therapy. A promising approach consists of differentiation of stem cells into insulin-producing cells (IPCs) in sufficient number and functional status to be transplanted. Differentiation protocols have been designed using consecutive cytokines or signaling modulator treatments, at specific dosages, to activate or inhibit the main signaling pathways that control the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic β-cells. Here, we provide an overview of the current approaches and achievements in obtaining stem cell-derived β-cells and the numerous challenges, which still need to be overcome to achieve this goal. Clinical translation of stem cells-derived β-cells for efficient maintenance of long-term euglycemia remains a major issue. Therefore, research efforts have been directed to the final steps of in vitro differentiation, aiming at production of functional and mature β-cells and integration of interdisciplinary fields to generate efficient cell therapy strategies capable of reversing the clinical outcome of T1D.
1 型糖尿病（T1D）是一种慢性疾病，其特征是胰岛素产生的β-胰腺细胞的自身免疫破坏。尽管在 T1D 治疗方面取得了许多进展，但目前的治疗策略往往无法维持血糖水平的完美控制。一些研究正在寻找新的和改进的方法，以体外扩增β细胞培养物，增加这些细胞用于胰岛替代治疗的供应。一种有前途的方法是将干细胞分化为具有足够数量和功能状态的胰岛素产生细胞（IPCs），以便进行移植。分化方案是使用连续的细胞因子或信号调节剂治疗，在特定剂量下，激活或抑制控制诱导多能干细胞（iPSCs）分化为胰腺β细胞的主要信号通路。在这里，我们概述了获得干细胞衍生β细胞的当前方法和成就，以及仍需要克服的许多挑战，以实现这一目标。临床转化干细胞衍生的β细胞以有效维持长期血糖正常仍然是一个主要问题。因此，研究工作一直致力于体外分化的最后阶段，旨在产生功能成熟的β细胞，并整合跨学科领域，以产生有效的细胞治疗策略，能够逆转 T1D 的临床结果。
