Abstract：
BACKGROUND: Creating induced pluripotent stem cells (iPSCs) from somatic cells of patients with genetic diseases offers a pathway to generate disease-specific iPSCs carrying genetic markers. Differentiating these iPSCs into renal tubular cells can aid in understanding the pathophysiology of rare inherited renal tubular diseases through cellular experiments.
METHODS: Two Japanese patients with Pseudohypoparathyroidism (PHP), a 49-year-old woman and a 71-year-old man, were studied. iPSC-derived tubular cells were established from their peripheral blood mononuclear cells (PBMCs). We examined changes in intracellular and extracellular cyclic adenosine monophosphate (cAMP) levels in these cells in response to parathyroid hormone (PTH) stimulation.
RESULTS: Renal tubular cells, differentiated from iPSCs of a healthy control (648A1), showed a PTH-dependent increase in both intracellular and extracellular cAMP levels. However, the renal tubular cells derived from the PHP patients\' iPSCs showed inconsistent changes in cAMP levels upon PTH exposure.
CONCLUSIONS: We successfully created disease-specific iPSCs from PHP patients\' PBMCs, differentiated them into tubular cells, and replicated the distinctive response of the disease to PTH in vitro. This approach could enhance our understanding of the pathophysiology of inherited renal tubular diseases and contribute to developing effective treatments.
METHODS: Two Japanese patients with Pseudohypoparathyroidism (PHP), a 49-year-old woman and a 71-year-old man, were studied. iPSC-derived tubular cells were established from their peripheral blood mononuclear cells (PBMCs). We examined changes in intracellular and extracellular cyclic adenosine monophosphate (cAMP) levels in these cells in response to parathyroid hormone (PTH) stimulation.
RESULTS: Renal tubular cells, differentiated from iPSCs of a healthy control (648A1), showed a PTH-dependent increase in both intracellular and extracellular cAMP levels. However, the renal tubular cells derived from the PHP patients\' iPSCs showed inconsistent changes in cAMP levels upon PTH exposure.
CONCLUSIONS: We successfully created disease-specific iPSCs from PHP patients\' PBMCs, differentiated them into tubular cells, and replicated the distinctive response of the disease to PTH in vitro. This approach could enhance our understanding of the pathophysiology of inherited renal tubular diseases and contribute to developing effective treatments.
摘要：
背景：从患有遗传疾病的患者的体细胞中产生诱导多能干细胞（iPSC）提供了产生携带遗传标记的疾病特异性iPSC的途径。将这些iPSC分化为肾小管细胞可以通过细胞实验帮助理解罕见遗传性肾小管疾病的病理生理学。
方法：两名日本假性甲状旁腺功能减退症（PHP）患者，一个49岁的女人和一个71岁的男人,被研究过。从其外周血单核细胞(PBMC)建立iPSC衍生的肾小管细胞。我们检查了这些细胞中对甲状旁腺激素（PTH）刺激的细胞内和细胞外环磷酸腺苷（cAMP）水平的变化。
结果：肾小管细胞，从健康对照（648A1）的iPSC分化，显示细胞内和细胞外cAMP水平的PTH依赖性增加。然而,来自PHP患者iPSCs的肾小管细胞在PTH暴露后显示cAMP水平变化不一致。
结论：我们成功地从PHP患者的PBMC中创建了疾病特异性iPSCs，将它们分化为肾小管细胞，并在体外复制了该疾病对PTH的独特反应。这种方法可以增强我们对遗传性肾小管疾病的病理生理学的理解，并有助于开发有效的治疗方法。
方法：两名日本假性甲状旁腺功能减退症（PHP）患者，一个49岁的女人和一个71岁的男人,被研究过。从其外周血单核细胞(PBMC)建立iPSC衍生的肾小管细胞。我们检查了这些细胞中对甲状旁腺激素（PTH）刺激的细胞内和细胞外环磷酸腺苷（cAMP）水平的变化。
结果：肾小管细胞，从健康对照（648A1）的iPSC分化，显示细胞内和细胞外cAMP水平的PTH依赖性增加。然而,来自PHP患者iPSCs的肾小管细胞在PTH暴露后显示cAMP水平变化不一致。
结论：我们成功地从PHP患者的PBMC中创建了疾病特异性iPSCs，将它们分化为肾小管细胞，并在体外复制了该疾病对PTH的独特反应。这种方法可以增强我们对遗传性肾小管疾病的病理生理学的理解，并有助于开发有效的治疗方法。
