TY - JOUR
T1 - In Vitro Modelling of Osteogenesis Imperfecta with Patient-Derived Induced Mesenchymal Stem Cells
AU - Claeys, Lauria
AU - Zhytnik, Lidiia
AU - Ventura, Laura
AU - Wisse, Lisanne E.
AU - Eekhoff, Elisabeth M.W.
AU - Pals, Gerard
AU - Bravenboer, Nathalie
AU - Heine, Vivi M.
AU - Micha, Dimitra
N1 - This article belongs to the Special Issue Stem Cells in Health and Disease 2.0) Publisher Copyright: © 2024 by the authors.
PY - 2024/3/2
Y1 - 2024/3/2
N2 - (1) Mesenchymal stem cells (MSCs) are a valuable cell model to study the bone pathology of Osteogenesis Imperfecta (OI), a rare genetic collagen-related disorder characterized by bone fragility and skeletal dysplasia. We aimed to generate a novel OI induced mesenchymal stem cell (iMSC) model from induced pluripotent stem cells (iPSCs) derived from human dermal fibroblasts. For the first time, OI iMSCs generation was based on an intermediate neural crest cell (iNCC) stage. (2) Skin fibroblasts from healthy individuals and OI patients were reprogrammed into iPSCs and subsequently differentiated into iMSCs via iNCCs. (3) Successful generation of iPSCs from acquired fibroblasts was confirmed with changes in cell morphology, expression of iPSC markers SOX2, NANOG, and OCT4 and three germ-layer tests. Following differentiation into iNCCs, cells presented increased iNCC markers including P75NTR, TFAP2A, and HNK-1 and decreased iPSC markers, shown to reach the iNCC stage. Induction into iMSCs was confirmed by the presence of CD73, CD105, and CD90 markers, low expression of the hematopoietic, and reduced expression of the iNCC markers. iMSCs were trilineage differentiation-competent, confirmed using molecular analyses and staining for cell-type-specific osteoblast, adipocyte, and chondrocyte markers. (4) In the current study, we have developed a multipotent in vitro iMSC model of OI patients and healthy controls able to differentiate into osteoblast-like cells.
AB - (1) Mesenchymal stem cells (MSCs) are a valuable cell model to study the bone pathology of Osteogenesis Imperfecta (OI), a rare genetic collagen-related disorder characterized by bone fragility and skeletal dysplasia. We aimed to generate a novel OI induced mesenchymal stem cell (iMSC) model from induced pluripotent stem cells (iPSCs) derived from human dermal fibroblasts. For the first time, OI iMSCs generation was based on an intermediate neural crest cell (iNCC) stage. (2) Skin fibroblasts from healthy individuals and OI patients were reprogrammed into iPSCs and subsequently differentiated into iMSCs via iNCCs. (3) Successful generation of iPSCs from acquired fibroblasts was confirmed with changes in cell morphology, expression of iPSC markers SOX2, NANOG, and OCT4 and three germ-layer tests. Following differentiation into iNCCs, cells presented increased iNCC markers including P75NTR, TFAP2A, and HNK-1 and decreased iPSC markers, shown to reach the iNCC stage. Induction into iMSCs was confirmed by the presence of CD73, CD105, and CD90 markers, low expression of the hematopoietic, and reduced expression of the iNCC markers. iMSCs were trilineage differentiation-competent, confirmed using molecular analyses and staining for cell-type-specific osteoblast, adipocyte, and chondrocyte markers. (4) In the current study, we have developed a multipotent in vitro iMSC model of OI patients and healthy controls able to differentiate into osteoblast-like cells.
KW - Osteogenesis Imperfecta
KW - bone
KW - cell model
KW - induced mesenchymal stem cells
KW - osteoblast
KW - skeletal dysplasia
UR - http://www.scopus.com/inward/record.url?scp=85189085831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85189085831&partnerID=8YFLogxK
U2 - 10.3390/ijms25063417
DO - 10.3390/ijms25063417
M3 - Article
C2 - 38542391
SN - 1661-6596
VL - 25
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 6
M1 - 3417
ER -