Orthotopic Bone Formation by Streamlined Engineering and Devitalization of Human Hypertrophic Cartilage.
Animals
Apoptosis
/ genetics
Bone Remodeling
/ genetics
Bone Substitutes
/ therapeutic use
Cartilage
/ growth & development
Cell Differentiation
/ genetics
Extracellular Matrix
/ genetics
Humans
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ cytology
Osteogenesis
/ genetics
Rabbits
Skull
/ growth & development
Tissue Engineering
/ methods
Tissue Scaffolds
Wound Healing
/ genetics
apoptosis
bioreactors
bone repair
endochondral ossification
hypertrophic cartilage
regenerative medicine
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Sep 2020
30 Sep 2020
Historique:
received:
02
09
2020
revised:
22
09
2020
accepted:
26
09
2020
entrez:
3
10
2020
pubmed:
4
10
2020
medline:
24
2
2021
Statut:
epublish
Résumé
Most bones of the human body form and heal through endochondral ossification, whereby hypertrophic cartilage (HyC) is formed and subsequently remodeled into bone. We previously demonstrated that HyC can be engineered from human mesenchymal stromal cells (hMSC), and subsequently devitalized by apoptosis induction. The resulting extracellular matrix (ECM) tissue retained osteoinductive properties, leading to ectopic bone formation. In this study, we aimed at engineering and devitalizing upscaled quantities of HyC ECM within a perfusion bioreactor, followed by in vivo assessment in an orthotopic bone repair model. We hypothesized that the devitalized HyC ECM would outperform a clinical product currently used for bone reconstructive surgery. Human MSC were genetically engineered with a gene cassette enabling apoptosis induction upon addition of an adjuvant. Engineered hMSC were seeded, differentiated, and devitalized within a perfusion bioreactor. The resulting HyC ECM was subsequently implanted in a 10-mm rabbit calvarial defect model, with processed human bone (Maxgraft
Identifiants
pubmed: 33008121
pii: ijms21197233
doi: 10.3390/ijms21197233
pmc: PMC7582540
pii:
doi:
Substances chimiques
Bone Substitutes
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Eurostars Program
ID : E!7865
Organisme : Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
ID : 310030-133110
Références
Transfus Med Hemother. 2012 Feb;39(1):36-40
pubmed: 22896765
Bone. 2016 Oct;91:30-8
pubmed: 27353702
Bone. 2015 Jan;70:66-72
pubmed: 25260931
Sci Transl Med. 2014 Apr 16;6(232):232fs16
pubmed: 24739757
Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3997-4002
pubmed: 23401508
Bone Joint J. 2016 Jan;98-B(1 Suppl A):6-9
pubmed: 26733632
Adv Drug Deliv Rev. 2015 Apr;84:1-29
pubmed: 25236302
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17426-31
pubmed: 25422415
Blood. 2013 Nov 14;122(20):3461-72
pubmed: 24016461
Nat Rev Endocrinol. 2016 Apr;12(4):203-21
pubmed: 26893264
Sports Med Arthrosc Rev. 2007 Sep;15(3):106-13
pubmed: 17700369
Biomaterials. 2019 Oct;218:119336
pubmed: 31310952
BMC Musculoskelet Disord. 2011 Jan 31;12:31
pubmed: 21281488
Semin Cell Dev Biol. 2008 Oct;19(5):459-66
pubmed: 18692584
Biomaterials. 2011 Apr;32(12):3233-43
pubmed: 21296410
Methods Mol Biol. 2016;1416:413-24
pubmed: 27236686
Adv Biochem Eng Biotechnol. 2013;129:73-88
pubmed: 22457052
Tissue Eng. 2007 Aug;13(8):2021-8
pubmed: 17590148
Stem Cells. 2014 Jun;32(6):1408-19
pubmed: 24578244
Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7251-6
pubmed: 20406908
Cell Tissue Bank. 2014 Sep;15(3):307-17
pubmed: 23999650
Tissue Eng Part A. 2009 Mar;15(3):635-43
pubmed: 18759673
J Biomech. 2008 Oct 20;41(14):2918-25
pubmed: 18789444
Toxicol Pathol. 2007 Jun;35(4):495-516
pubmed: 17562483
Adv Drug Deliv Rev. 2018 Apr;129:285-294
pubmed: 29357301
Stem Cells. 2005 Sep;23(8):1066-72
pubmed: 16002780
J Tissue Eng Regen Med. 2016 Apr;10(4):E250-62
pubmed: 23922276
Tissue Eng Part B Rev. 2014 Dec;20(6):596-608
pubmed: 24749845
J Cell Biochem. 2014 Jun;115(6):1089-96
pubmed: 24357502
J Tissue Eng Regen Med. 2015 Aug;9(8):889-902
pubmed: 24916192
Biomaterials. 2013 Aug;34(26):6099-108
pubmed: 23721795
Nat Rev Rheumatol. 2015 Jan;11(1):45-54
pubmed: 25266456
Glycobiology. 2003 Sep;13(9):647-53
pubmed: 12773478
Stem Cell Res Ther. 2015 Apr 23;6:84
pubmed: 25900045
Tissue Eng Part A. 2009 Mar;15(3):625-34
pubmed: 18759672
Bone. 2011 Feb;48(2):171-81
pubmed: 20932947
Nat Methods. 2013 Aug;10(8):788-94
pubmed: 23793238
Trends Mol Med. 2011 Aug;17(8):424-32
pubmed: 21514224
Biotechnol J. 2013 Jun;8(6):644-54
pubmed: 23625834