Generation of a human induced pluripotent stem cell line (BIHi002-A) from a patient with CLCN7-related infantile malignant autosomal recessive osteopetrosis

Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7-related osteopetrosis

“…( 25 ) The child deceased at the age of 14 months as a consequence of progressive respiratory failure. Given the exceptional phenotype of ARO, with predominant neurological symptoms and impaired cortical development, we decided to generate ARO hiPSCs from blood cells for follow‐up investigations (cell line BIHi002‐A ( 16 ) ).…”

“…(32) To demonstrate the usability of our osteoclast differentiation protocol for functional investigations, we applied it to the patient-derived osteopetrotic hiPSC line BIHi002-A. (16) The donor was diagnosed with ARO by a chest x-ray at the age of 7 months. Before this, the failure to thrive and neurological symptoms beginning at 4 months of age were interpreted as signs of a mitochondriopathy or a lysosomal storage disease.…”

“…Osteoclast‐related experiments were performed using hiPSC lines BIHi001‐A and BIHi004‐A (https://hpscreg.eu/cell-line/BIHi001-A, https://hpscreg.eu/cell-line/BIHi004-A, kindly provided by the BIH Core Facility Stem Cells), 10211.EURCC, UMGi014‐C clone 14, and UMGi020‐B clone 21 (isWT1.14 and isWT7.21 respectively, https://hpscreg.eu/cell-line/UMGi014-C, https://hpscreg.eu/cell-line/UMGi020-B, kindly provided by the UMG Stem Cell Unit) from control donors as well as osteopetrosis patient‐derived cell lines BIHi002‐A, ( 16 ) BIHi002‐B, and BIHi002‐C. Origins and reprogramming methods of the hiPSC lines are listed in Table S1.…”

Autosomal recessive osteopetrosis: mechanisms and treatments

“…ARO caused by osteoclast-extrinsic deficiency, such as in the case of TNFSF11 mutations, requires a different approach, because defective cells are not of hematopoietic origin. RANKL replacement therapy has been explored in Tnfsf11 −/− mice, Neri et al, 2015Chen et al, 2019Xian et al, 2020Hennig et al, 2019Rossler et al, 2018 Non-genotoxic conditioning To be tested in ARO --ARO, autosomal recessive osteopetrosis; HSCT, hematopoietic stem cell transplantation; iPSC, induced pluripotent stem cell; NSG, non-obese diabetic severe combined immunodeficiency Il2rγ −/− ; RANKL, receptor activator of nuclear factor kappa-B ligand.…”

“…In the past decades, patient-derived induced pluripotent stem cells (iPSCs) have been extensively applied to investigate the pathobiology of different diseases and to test innovative treatments, thereby overcoming the limitations imposed by the availability of specimens from patients. An iPSC line generated from a CLCN7-defective ARO patient was used to test the integration of the Sleeping Beauty transposon (Box 1) carrying CLCN7 cDNA (Hennig et al, 2019;Rossler, 2018).…”