Neural crest-derived mesenchymal progenitor cells enhance cranial allograft integration

Autor: Zulma Gazit, Wafa Tawackoli, Robert H. Baloh, Melodie F. Metzger, Angela Papalamprou, Juliane D. Glaeser, Samuel Eberlein, Tina Stefanovic, Trevor J. Nelson, Doron Cohn‐Schwartz, Shiran Ben-David, Dmitriy Sheyn, Khosrowdad Salehi, Robert K. Ryu, Kevin J. Kim, Hyun W. Bae, Yasaman Arabi, Phillip H. Behrens
Rok vydání: 2021
Předmět:
0301 basic medicine
allograft
Pathology
Mice
SCID
Mice
0302 clinical medicine
Mice
Inbred NOD
Tissue‐specific Progenitor and Stem Cells
cranial repair
neural crest cells
lcsh:R5-920
biology
lcsh:Cytology
Neural crest
Cell Differentiation
General Medicine
Allografts
Neural Crest
Osteocalcin
bone healing
lcsh:Medicine (General)
Cell type
medicine.medical_specialty
Induced Pluripotent Stem Cells
Bone Marrow Cells
Bone healing
Mesenchymal Stem Cell Transplantation
MSC
03 medical and health sciences
Osseointegration
Bone-Implant Interface
medicine
Animals
Humans
Bioluminescence imaging
lcsh:QH573-671
Progenitor cell
Severe combined immunodeficiency
business.industry
Skull
Mesenchymal stem cell
Mesenchymal Stem Cells
X-Ray Microtomography
Cell Biology
medicine.disease
030104 developmental biology
biology.protein
business
030217 neurology & neurosurgery
Developmental Biology
Zdroj: Stem Cells Translational Medicine
Stem Cells Translational Medicine, Vol 10, Iss 5, Pp 797-809 (2021)
ISSN: 2157-6580
2157-6564
Popis: 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.
Bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) were obtained from human bone marrow. Induced neural crest cell‐mesenchymal progenitor cells (iNCC‐MPCs) were generated from induced pluripotent stem cell‐derived iNCCs. Cells were luciferase transfected and seeded onto decellularized allografts, which were implanted into 5 mm circular calvarial defects in non‐obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Allograft only was used as controls. Mice were followed for a duration of 8 weeks. Cell survival, allograft integration, and tissue morphology and transplanted cell contribution were monitored via bioluminescence imaging (BLI), micro‐computed tomography (μCT), and histology and immunofluorescence (IF). Green arrow: BLI; yellow arrow: μCT; Orange arrow: histology and IF; Blue arrow: biomechanical test.
Databáze: OpenAIRE
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