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Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen

[Display omitted] Bioactive functional scaffolds are essential for support of cell-based strategies to improve bone regeneration. Adipose-tissue-derived-stromal cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential...

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Published in:Acta biomaterialia 2018-08, Vol.76, p.135-145
Main Authors: Bothe, Friederike, Lotz, Benedict, Seebach, Elisabeth, Fischer, Jennifer, Hesse, Eliane, Diederichs, Solvig, Richter, Wiltrud
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cited_by cdi_FETCH-LOGICAL-c390t-e526c2d4e3db36b41d642a9019f3319767d1ac22109e1567a9fce07ef072e1213
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container_start_page 135
container_title Acta biomaterialia
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creator Bothe, Friederike
Lotz, Benedict
Seebach, Elisabeth
Fischer, Jennifer
Hesse, Eliane
Diederichs, Solvig
Richter, Wiltrud
description [Display omitted] Bioactive functional scaffolds are essential for support of cell-based strategies to improve bone regeneration. Adipose-tissue-derived-stromal cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential to replace BMSC for therapeutic stimulation of bone-defect healing. Their osteogenic potential is, however, lower compared to BMSC, a deficit that may be overcome in growth factor-rich orthotopic bone defects with enhanced bone-conductive scaffolds. Objective of this study was to compare the therapeutic potency of human ASC and BMSC for bone regeneration on a novel nanoparticulate β-TCP/collagen-carrier (β-TNC). Cytotoxicity of β-TCP nanoparticles and multilineage differentiation of cells were characterized in vitro. Cell-seeded β-TNC versus cell-free controls were implanted into 4 mm calvarial bone-defects in immunodeficient mice and bone healing was quantified by µCT at 4 and 8 weeks. Tissue-quality and cell-origin were assessed by histology. β-TNC was non-toxic, radiolucent and biocompatible, lent excellent support for human cell persistence and allowed formation of human bone tissue by BMSC but not ASC. Opposite to BMSC, ASC-grafting significantly inhibited calvarial bone healing compared to controls. Bone formation progressed significantly from 4 to 8 weeks only in BMSC and controls yielding 5.6-fold more mineralized tissue in BMSC versus ASC-treated defects. Conclusively, β-TNC was simple to generate, biocompatible, osteoconductive, and stimulated osteogenicity of BMSC to enhance calvarial defect healing while ASC had negative effects. Thus, an orthotopic environment and β-TNC could not compensate for cell-autonomous deficits of ASC which should systematically be considered when choosing the right cell source for tissue engineering-based stimulation of bone regeneration. Bone-marrow-derived-stromal cells (BMSC) implanted on bone replacement materials can support bone defect healing and adipose-tissue-derived-stromal cells (ASC) being more accessible and better proliferating are considered as alternate source. This first standardized comparison of the bone regeneration potency of human ASC and BMSC was performed on a novel nanoparticular β-TCP-enriched collagen-carrier (β-TNC) designed to overcome the known inferior osteogenicity of ASC. β-TNC was non-toxic, biocompatible and osteoconductive supporting human bone formation and defect-closure by BMSC but not
doi_str_mv 10.1016/j.actbio.2018.06.026
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Adipose-tissue-derived-stromal cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential to replace BMSC for therapeutic stimulation of bone-defect healing. Their osteogenic potential is, however, lower compared to BMSC, a deficit that may be overcome in growth factor-rich orthotopic bone defects with enhanced bone-conductive scaffolds. Objective of this study was to compare the therapeutic potency of human ASC and BMSC for bone regeneration on a novel nanoparticulate β-TCP/collagen-carrier (β-TNC). Cytotoxicity of β-TCP nanoparticles and multilineage differentiation of cells were characterized in vitro. Cell-seeded β-TNC versus cell-free controls were implanted into 4 mm calvarial bone-defects in immunodeficient mice and bone healing was quantified by µCT at 4 and 8 weeks. Tissue-quality and cell-origin were assessed by histology. β-TNC was non-toxic, radiolucent and biocompatible, lent excellent support for human cell persistence and allowed formation of human bone tissue by BMSC but not ASC. Opposite to BMSC, ASC-grafting significantly inhibited calvarial bone healing compared to controls. Bone formation progressed significantly from 4 to 8 weeks only in BMSC and controls yielding 5.6-fold more mineralized tissue in BMSC versus ASC-treated defects. Conclusively, β-TNC was simple to generate, biocompatible, osteoconductive, and stimulated osteogenicity of BMSC to enhance calvarial defect healing while ASC had negative effects. Thus, an orthotopic environment and β-TNC could not compensate for cell-autonomous deficits of ASC which should systematically be considered when choosing the right cell source for tissue engineering-based stimulation of bone regeneration. Bone-marrow-derived-stromal cells (BMSC) implanted on bone replacement materials can support bone defect healing and adipose-tissue-derived-stromal cells (ASC) being more accessible and better proliferating are considered as alternate source. This first standardized comparison of the bone regeneration potency of human ASC and BMSC was performed on a novel nanoparticular β-TCP-enriched collagen-carrier (β-TNC) designed to overcome the known inferior osteogenicity of ASC. β-TNC was non-toxic, biocompatible and osteoconductive supporting human bone formation and defect-closure by BMSC but not ASC. Long-term cell-persistence and the distinct secretome of ASC appear as main reasons why ASC inhibited bone healing opposite to BMSC. Overall, ASC-grafting is at considerable risk of producing negative effects on bone-healing while no such risks are known for BMSC.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2018.06.026</identifier><identifier>PMID: 29933108</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Accessibility ; Adipose Tissue - metabolism ; Adipose Tissue - pathology ; Adipose tissue-derived stromal cells ; Animals ; Biocompatibility ; Biomedical materials ; Bone growth ; Bone healing ; Bone marrow ; Bone Marrow Cells - metabolism ; Bone Marrow Cells - pathology ; Bone-marrow-derived mesenchymal stromal cells ; Calcium Phosphates - chemistry ; Calcium Phosphates - pharmacology ; Calvarial bone regeneration ; Cell growth ; Cell proliferation ; Collagen ; Cytotoxicity ; Defects ; Differentiation (biology) ; Environmental effects ; Female ; Fracture Healing ; Grafting ; Growth factors ; Healing ; Histology ; Humans ; Immunodeficiency ; Mice ; Mice, SCID ; Nanoparticles ; Nanoparticles - chemistry ; Nanoparticles - therapeutic use ; Osteoconduction ; Osteogenesis ; Quality assessment ; Regeneration ; Regeneration (physiology) ; Scaffolds ; Secretome ; Skull - injuries ; Skull - metabolism ; Skull - pathology ; Stimulation ; Stromal cells ; Stromal Cells - metabolism ; Stromal Cells - pathology ; Stromal Cells - transplantation ; Tissue engineering ; Toxicity ; Wound healing ; β-TCP</subject><ispartof>Acta biomaterialia, 2018-08, Vol.76, p.135-145</ispartof><rights>2018 Acta Materialia Inc.</rights><rights>Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier BV Aug 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-e526c2d4e3db36b41d642a9019f3319767d1ac22109e1567a9fce07ef072e1213</citedby><cites>FETCH-LOGICAL-c390t-e526c2d4e3db36b41d642a9019f3319767d1ac22109e1567a9fce07ef072e1213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29933108$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bothe, Friederike</creatorcontrib><creatorcontrib>Lotz, Benedict</creatorcontrib><creatorcontrib>Seebach, Elisabeth</creatorcontrib><creatorcontrib>Fischer, Jennifer</creatorcontrib><creatorcontrib>Hesse, Eliane</creatorcontrib><creatorcontrib>Diederichs, Solvig</creatorcontrib><creatorcontrib>Richter, Wiltrud</creatorcontrib><title>Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted] Bioactive functional scaffolds are essential for support of cell-based strategies to improve bone regeneration. Adipose-tissue-derived-stromal cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential to replace BMSC for therapeutic stimulation of bone-defect healing. Their osteogenic potential is, however, lower compared to BMSC, a deficit that may be overcome in growth factor-rich orthotopic bone defects with enhanced bone-conductive scaffolds. Objective of this study was to compare the therapeutic potency of human ASC and BMSC for bone regeneration on a novel nanoparticulate β-TCP/collagen-carrier (β-TNC). Cytotoxicity of β-TCP nanoparticles and multilineage differentiation of cells were characterized in vitro. Cell-seeded β-TNC versus cell-free controls were implanted into 4 mm calvarial bone-defects in immunodeficient mice and bone healing was quantified by µCT at 4 and 8 weeks. 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Bone-marrow-derived-stromal cells (BMSC) implanted on bone replacement materials can support bone defect healing and adipose-tissue-derived-stromal cells (ASC) being more accessible and better proliferating are considered as alternate source. This first standardized comparison of the bone regeneration potency of human ASC and BMSC was performed on a novel nanoparticular β-TCP-enriched collagen-carrier (β-TNC) designed to overcome the known inferior osteogenicity of ASC. β-TNC was non-toxic, biocompatible and osteoconductive supporting human bone formation and defect-closure by BMSC but not ASC. Long-term cell-persistence and the distinct secretome of ASC appear as main reasons why ASC inhibited bone healing opposite to BMSC. 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Adipose-tissue-derived-stromal cells (ASC) are more accessible multipotent cells with faster proliferation than bone-marrow-derived-stromal-cells (BMSC) having potential to replace BMSC for therapeutic stimulation of bone-defect healing. Their osteogenic potential is, however, lower compared to BMSC, a deficit that may be overcome in growth factor-rich orthotopic bone defects with enhanced bone-conductive scaffolds. Objective of this study was to compare the therapeutic potency of human ASC and BMSC for bone regeneration on a novel nanoparticulate β-TCP/collagen-carrier (β-TNC). Cytotoxicity of β-TCP nanoparticles and multilineage differentiation of cells were characterized in vitro. Cell-seeded β-TNC versus cell-free controls were implanted into 4 mm calvarial bone-defects in immunodeficient mice and bone healing was quantified by µCT at 4 and 8 weeks. Tissue-quality and cell-origin were assessed by histology. β-TNC was non-toxic, radiolucent and biocompatible, lent excellent support for human cell persistence and allowed formation of human bone tissue by BMSC but not ASC. Opposite to BMSC, ASC-grafting significantly inhibited calvarial bone healing compared to controls. Bone formation progressed significantly from 4 to 8 weeks only in BMSC and controls yielding 5.6-fold more mineralized tissue in BMSC versus ASC-treated defects. Conclusively, β-TNC was simple to generate, biocompatible, osteoconductive, and stimulated osteogenicity of BMSC to enhance calvarial defect healing while ASC had negative effects. Thus, an orthotopic environment and β-TNC could not compensate for cell-autonomous deficits of ASC which should systematically be considered when choosing the right cell source for tissue engineering-based stimulation of bone regeneration. Bone-marrow-derived-stromal cells (BMSC) implanted on bone replacement materials can support bone defect healing and adipose-tissue-derived-stromal cells (ASC) being more accessible and better proliferating are considered as alternate source. This first standardized comparison of the bone regeneration potency of human ASC and BMSC was performed on a novel nanoparticular β-TCP-enriched collagen-carrier (β-TNC) designed to overcome the known inferior osteogenicity of ASC. β-TNC was non-toxic, biocompatible and osteoconductive supporting human bone formation and defect-closure by BMSC but not ASC. Long-term cell-persistence and the distinct secretome of ASC appear as main reasons why ASC inhibited bone healing opposite to BMSC. Overall, ASC-grafting is at considerable risk of producing negative effects on bone-healing while no such risks are known for BMSC.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>29933108</pmid><doi>10.1016/j.actbio.2018.06.026</doi><tpages>11</tpages></addata></record>
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identifier ISSN: 1742-7061
ispartof Acta biomaterialia, 2018-08, Vol.76, p.135-145
issn 1742-7061
1878-7568
language eng
recordid cdi_proquest_miscellaneous_2058508346
source ScienceDirect Journals
subjects Accessibility
Adipose Tissue - metabolism
Adipose Tissue - pathology
Adipose tissue-derived stromal cells
Animals
Biocompatibility
Biomedical materials
Bone growth
Bone healing
Bone marrow
Bone Marrow Cells - metabolism
Bone Marrow Cells - pathology
Bone-marrow-derived mesenchymal stromal cells
Calcium Phosphates - chemistry
Calcium Phosphates - pharmacology
Calvarial bone regeneration
Cell growth
Cell proliferation
Collagen
Cytotoxicity
Defects
Differentiation (biology)
Environmental effects
Female
Fracture Healing
Grafting
Growth factors
Healing
Histology
Humans
Immunodeficiency
Mice
Mice, SCID
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - therapeutic use
Osteoconduction
Osteogenesis
Quality assessment
Regeneration
Regeneration (physiology)
Scaffolds
Secretome
Skull - injuries
Skull - metabolism
Skull - pathology
Stimulation
Stromal cells
Stromal Cells - metabolism
Stromal Cells - pathology
Stromal Cells - transplantation
Tissue engineering
Toxicity
Wound healing
β-TCP
title Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T01%3A19%3A43IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Stimulation%20of%20calvarial%20bone%20healing%20with%20human%20bone%20marrow%20stromal%20cells%20versus%20inhibition%20with%20adipose-tissue%20stromal%20cells%20on%20nanostructured%20%CE%B2-TCP-collagen&rft.jtitle=Acta%20biomaterialia&rft.au=Bothe,%20Friederike&rft.date=2018-08&rft.volume=76&rft.spage=135&rft.epage=145&rft.pages=135-145&rft.issn=1742-7061&rft.eissn=1878-7568&rft_id=info:doi/10.1016/j.actbio.2018.06.026&rft_dat=%3Cproquest_cross%3E2114220424%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c390t-e526c2d4e3db36b41d642a9019f3319767d1ac22109e1567a9fce07ef072e1213%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2114220424&rft_id=info:pmid/29933108&rfr_iscdi=true