Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration.
Allografts
Animals
Bone Marrow Cells
Bone-Implant Interface
Cell Differentiation
Humans
Induced Pluripotent Stem Cells
/ cytology
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ cytology
Mice
Mice, Inbred NOD
Mice, SCID
Neural Crest
/ cytology
Osseointegration
Skull
/ diagnostic imaging
X-Ray Microtomography
MSC
allograft
bone healing
cranial repair
neural crest cells
Journal
Stem cells translational medicine
ISSN: 2157-6580
Titre abrégé: Stem Cells Transl Med
Pays: England
ID NLM: 101578022
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
revised:
10
10
2020
received:
03
08
2020
accepted:
09
11
2020
pubmed:
30
1
2021
medline:
24
3
2022
entrez:
29
1
2021
Statut:
ppublish
Résumé
Replacement of lost cranial bone (partly mesodermal and partly neural crest-derived) is challenging and includes the use of nonviable allografts. To revitalize allografts, bone marrow-derived mesenchymal stromal cells (mesoderm-derived BM-MSCs) have been used with limited success. We hypothesize that coating of allografts with induced neural crest cell-mesenchymal progenitor cells (iNCC-MPCs) improves implant-to-bone integration in mouse cranial defects. Human induced pluripotent stem cells were reprogramed from dermal fibroblasts, differentiated to iNCCs and then to iNCC-MPCs. BM-MSCs were used as reference. Cells were labeled with luciferase (Luc2) and characterized for MSC consensus markers expression, differentiation, and risk of cellular transformation. A calvarial defect was created in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and allografts were implanted, with or without cell coating. Bioluminescence imaging (BLI), microcomputed tomography (μCT), histology, immunofluorescence, and biomechanical tests were performed. Characterization of iNCC-MPC-Luc2 vs BM-MSC-Luc2 showed no difference in MSC markers expression and differentiation in vitro. In vivo, BLI indicated survival of both cell types for at least 8 weeks. At week 8, μCT analysis showed enhanced structural parameters in the iNCC-MPC-Luc2 group and increased bone volume in the BM-MSC-Luc2 group compared to controls. Histology demonstrated improved integration of iNCC-MPC-Luc2 allografts compared to BM-MSC-Luc2 group and controls. Human osteocalcin and collagen type 1 were detected at the allograft-host interphase in cell-seeded groups. The iNCC-MPC-Luc2 group also demonstrated improved biomechanical properties compared to BM-MSC-Luc2 implants and cell-free controls. Our results show an improved integration of iNCC-MPC-Luc2-coated allografts compared to BM-MSC-Luc2 and controls, suggesting the use of iNCC-MPCs as potential cell source for cranial bone repair.
Identifiants
pubmed: 33512772
doi: 10.1002/sctm.20-0364
pmc: PMC8046069
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
797-809Subventions
Organisme : NIAMS NIH HHS
ID : K01 AR071512
Pays : United States
Informations de copyright
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
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