Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration
Abstract 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 hypoth...
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Wiley
2021-05-01
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Series: | Stem Cells Translational Medicine |
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Online Access: | https://doi.org/10.1002/sctm.20-0364 |
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doaj-623fd8f367c6432984c32584341c5193 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juliane D. Glaeser Phillip Behrens Tina Stefanovic Khosrowdad Salehi Angela Papalamprou Wafa Tawackoli Melodie F. Metzger Samuel Eberlein Trevor Nelson Yasaman Arabi Kevin Kim Robert H. Baloh Shiran Ben‐David Doron Cohn‐Schwartz Robert Ryu Hyun W. Bae Zulma Gazit Dmitriy Sheyn |
spellingShingle |
Juliane D. Glaeser Phillip Behrens Tina Stefanovic Khosrowdad Salehi Angela Papalamprou Wafa Tawackoli Melodie F. Metzger Samuel Eberlein Trevor Nelson Yasaman Arabi Kevin Kim Robert H. Baloh Shiran Ben‐David Doron Cohn‐Schwartz Robert Ryu Hyun W. Bae Zulma Gazit Dmitriy Sheyn Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration Stem Cells Translational Medicine allograft bone healing cranial repair MSC neural crest cells |
author_facet |
Juliane D. Glaeser Phillip Behrens Tina Stefanovic Khosrowdad Salehi Angela Papalamprou Wafa Tawackoli Melodie F. Metzger Samuel Eberlein Trevor Nelson Yasaman Arabi Kevin Kim Robert H. Baloh Shiran Ben‐David Doron Cohn‐Schwartz Robert Ryu Hyun W. Bae Zulma Gazit Dmitriy Sheyn |
author_sort |
Juliane D. Glaeser |
title |
Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
title_short |
Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
title_full |
Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
title_fullStr |
Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
title_full_unstemmed |
Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
title_sort |
neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integration |
publisher |
Wiley |
series |
Stem Cells Translational Medicine |
issn |
2157-6564 2157-6580 |
publishDate |
2021-05-01 |
description |
Abstract 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. |
topic |
allograft bone healing cranial repair MSC neural crest cells |
url |
https://doi.org/10.1002/sctm.20-0364 |
work_keys_str_mv |
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doaj-623fd8f367c6432984c32584341c51932021-04-14T16:20:02ZengWileyStem Cells Translational Medicine2157-65642157-65802021-05-0110579780910.1002/sctm.20-0364Neural crest‐derived mesenchymal progenitor cells enhance cranial allograft integrationJuliane D. Glaeser0Phillip Behrens1Tina Stefanovic2Khosrowdad Salehi3Angela Papalamprou4Wafa Tawackoli5Melodie F. Metzger6Samuel Eberlein7Trevor Nelson8Yasaman Arabi9Kevin Kim10Robert H. Baloh11Shiran Ben‐David12Doron Cohn‐Schwartz13Robert Ryu14Hyun W. Bae15Zulma Gazit16Dmitriy Sheyn17Orthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USADepartment of Orthopedics Cedars‐Sinai Medical Center Los Angeles California USADepartment of Orthopedics Cedars‐Sinai Medical Center Los Angeles California USADepartment of Orthopedics Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USADepartment of Surgery Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USAOrthopaedic Stem Cell Research Laboratory Cedars‐Sinai Medical Center Los Angeles California USAAbstract 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.https://doi.org/10.1002/sctm.20-0364allograftbone healingcranial repairMSCneural crest cells |