Generation of gene-corrected functional osteoclasts from osteopetrotic induced pluripotent stem cells
(2020) In Stem Cell Research & Therapy 11.- Abstract
BACKGROUND: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. METHODS: IMO iPSCs were generated from a patient carrying a homozygous c.11279G>A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIRG1. Embryoid bodies were generated and differentiated into monocytes. Non-adherent cells were harvested and further differentiated into osteoclasts on bovine bone slices. RESULTS: Release of the bone resorption biomarker CTX-I into the media of gene-corrected osteoclasts was 5-fold higher than that of the uncorrected osteoclasts and 35% of... (More)
BACKGROUND: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. METHODS: IMO iPSCs were generated from a patient carrying a homozygous c.11279G>A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIRG1. Embryoid bodies were generated and differentiated into monocytes. Non-adherent cells were harvested and further differentiated into osteoclasts on bovine bone slices. RESULTS: Release of the bone resorption biomarker CTX-I into the media of gene-corrected osteoclasts was 5-fold higher than that of the uncorrected osteoclasts and 35% of that of control osteoclasts. Bone resorption potential was confirmed by the presence of pits on the bones cultured with gene-corrected osteoclasts, absent in the uncorrected IMO osteoclasts. CONCLUSIONS: The disease phenotype was partially corrected in vitro, providing a valuable resource for therapy development for this form of severe osteopetrosis.
(Less)
- author
- Xian, Xiaojie
LU
; Moraghebi, Roksana
LU
; Löfvall, Henrik
LU
; Fasth, Anders ; Henriksen, Kim ; Richter, Johan LU ; Woods, Niels Bjarne LU and Moscatelli, Ilana LU
- organization
- publishing date
- 2020-05-15
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Gene transfer, Infantile malignant osteopetrosis, iPSC generation, Osteoclast differentiation
- in
- Stem Cell Research & Therapy
- volume
- 11
- article number
- 179
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:32414402
- scopus:85084787210
- ISSN
- 1757-6512
- DOI
- 10.1186/s13287-020-01701-y
- language
- English
- LU publication?
- yes
- id
- b5f46c64-8326-49c1-b163-edca5984240d
- date added to LUP
- 2020-06-16 15:23:11
- date last changed
- 2024-05-01 11:27:27
@article{b5f46c64-8326-49c1-b163-edca5984240d, abstract = {{<p>BACKGROUND: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene. METHODS: IMO iPSCs were generated from a patient carrying a homozygous c.11279G>A (IVS18+1) mutation in TCIRG1 and transduced with a lentiviral vector expressing human TCIRG1. Embryoid bodies were generated and differentiated into monocytes. Non-adherent cells were harvested and further differentiated into osteoclasts on bovine bone slices. RESULTS: Release of the bone resorption biomarker CTX-I into the media of gene-corrected osteoclasts was 5-fold higher than that of the uncorrected osteoclasts and 35% of that of control osteoclasts. Bone resorption potential was confirmed by the presence of pits on the bones cultured with gene-corrected osteoclasts, absent in the uncorrected IMO osteoclasts. CONCLUSIONS: The disease phenotype was partially corrected in vitro, providing a valuable resource for therapy development for this form of severe osteopetrosis.</p>}}, author = {{Xian, Xiaojie and Moraghebi, Roksana and Löfvall, Henrik and Fasth, Anders and Henriksen, Kim and Richter, Johan and Woods, Niels Bjarne and Moscatelli, Ilana}}, issn = {{1757-6512}}, keywords = {{Gene transfer; Infantile malignant osteopetrosis; iPSC generation; Osteoclast differentiation}}, language = {{eng}}, month = {{05}}, publisher = {{BioMed Central (BMC)}}, series = {{Stem Cell Research & Therapy}}, title = {{Generation of gene-corrected functional osteoclasts from osteopetrotic induced pluripotent stem cells}}, url = {{http://dx.doi.org/10.1186/s13287-020-01701-y}}, doi = {{10.1186/s13287-020-01701-y}}, volume = {{11}}, year = {{2020}}, }