Induced pluripotent stem cells derived renal tubular cells from a patient with pseudohypoparathyroidism and its response to parathyroid hormone stimulation

期刊论文
发表日期：

2024年7月11日

查看全文

Yoshihiro Nakamura,
Hiroki Kobayashi,
Noboru Fukuda,
Sho Tanaka,
Yusuke Murata,
Yoshinari Hatanaka,
Akira Haketa,
Akiko Tsunemi,
Lan Chen,
Masanori Abe

摘要

Introduction

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.

Materials and 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.

Conclusion

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.