Bone marrow mesenchymal stem cells combined with ultra-purified alginate gel as a regenerative therapeutic strategy after discectomy for degenerated intervertebral discs.
Biomaterial
Bone marrow mesenchymal stem cell
Herniated disc
Intervertebral disc
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Mar 2020
Mar 2020
Historique:
received:
01
01
2020
revised:
07
02
2020
accepted:
18
02
2020
pubmed:
7
3
2020
medline:
18
12
2020
entrez:
7
3
2020
Statut:
ppublish
Résumé
Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs. Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs. Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs. These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs. Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
Sections du résumé
BACKGROUND
BACKGROUND
Because the regenerative ability of intervertebral discs (IVDs) is restricted, defects caused by discectomy may induce insufficient tissue repair leading to further IVD degeneration. An acellular bioresorbable biomaterial based on ultra-purified alginate (UPAL) gel was developed to fill the IVD cavity and prevent IVD degeneration. However, an acellular matrix-based strategy may have limitations, particularly in the elderly population, who exhibit low self-repair capability. Therefore, further translational studies involving product combinations, such as UPAL gel plus bone marrow-derived mesenchymal stem cells (BMSCs), are required to evaluate the regenerative effects of BMSCs embedded in UPAL gel on degenerated IVDs.
METHODS
METHODS
Rabbit BMSCs and nucleus pulposus cells (NPCs) were co-cultured in a three-dimensional (3D) system in UPAL gel. In addition, rabbit or human BMSCs combined with UPAL gel were implanted into IVDs following partial discectomy in rabbits with degenerated IVDs.
FINDINGS
RESULTS
Gene expression of NPC markers, growth factors, and extracellular matrix was significantly increased in the NPC and BMSC 3D co-culture compared to that in each 3D mono-culture. In vivo, whereas UPAL gel alone suppressed IVD degeneration as compared to discectomy, the combination of BMSCs and UPAL gel exerted a more potent effect to induce IVD regeneration. Similar IVD regeneration was observed using human BMSCs.
INTERPRETATION
CONCLUSIONS
These findings demonstrate the therapeutic potential of BMSCs combined with UPAL gel as a regenerative strategy following discectomy for degenerated IVDs.
FUNDING
BACKGROUND
Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.
Identifiants
pubmed: 32143180
pii: S2352-3964(20)30073-6
doi: 10.1016/j.ebiom.2020.102698
pmc: PMC7057222
pii:
doi:
Substances chimiques
Alginates
0
Hydrogels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
102698Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest Patents pertaining to this work have been filed (inventors H. S., T. T., and N. I.). The other authors declare that they have no competing interests.
Références
J Orthop Res. 2008 May;26(5):589-600
pubmed: 18203202
Eur Spine J. 2018 Oct;27(10):2639-2649
pubmed: 30141058
Arthritis Res Ther. 2012 Feb 07;14(1):R31
pubmed: 22314040
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Spine (Phila Pa 1976). 2008 Aug 15;33(18):1951-7
pubmed: 18708927
Spine (Phila Pa 1976). 1998 Jul 15;23(14):1531-8; discussion 1539
pubmed: 9682309
Pain Physician. 2019 Jul;22(4):353-360
pubmed: 31337166
Am J Transl Res. 2017 Mar 15;9(3):900-909
pubmed: 28386320
Tissue Eng Part C Methods. 2012 Feb;18(2):156-65
pubmed: 21951128
J Orthop Res. 2017 Jan;35(1):61-73
pubmed: 27699833
Regen Med. 2010 Sep;5(5):701-11
pubmed: 20868326
Biochem Soc Trans. 2007 Aug;35(Pt 4):652-5
pubmed: 17635113
Spine (Phila Pa 1976). 2005 Nov 1;30(21):2379-87
pubmed: 16261113
J Orthop Res. 2010 Oct;28(10):1267-75
pubmed: 20839317
Stem Cells Int. 2012;2012:658356
pubmed: 22701494
Am J Pathol. 2014 Mar;184(3):753-64
pubmed: 24389166
Transplantation. 2017 Aug;101(8):1945-1951
pubmed: 27661661
J Orthop Res. 2019 Sep;37(9):1963-1971
pubmed: 31106893
J Neurosurg Spine. 2014 Jun;20(6):657-69
pubmed: 24702507
Tissue Eng Part A. 2015 Jan;21(1-2):288-99
pubmed: 25060596
Spine (Phila Pa 1976). 2001 Sep 1;26(17):1873-8
pubmed: 11568697
J Orthop Res. 2015 Mar;33(3):283-93
pubmed: 25411088
Stem Cells. 2006 Mar;24(3):707-16
pubmed: 16223853
J Tissue Eng Regen Med. 2012 May;6(5):348-55
pubmed: 21671407
Tissue Eng Part A. 2014 Mar;20(5-6):908-20
pubmed: 24102374
Biomaterials. 2006 Jan;27(3):335-45
pubmed: 16112726
Stem Cells Int. 2019 Oct 15;2019:8496025
pubmed: 31737077
Spine (Phila Pa 1976). 2004 Dec 1;29(23):2627-32
pubmed: 15564911
Arthritis Rheum. 2011 Jun;63(6):1648-57
pubmed: 21305515
Tissue Eng Part A. 2014 May;20(9-10):1379-91
pubmed: 24372278
EBioMedicine. 2018 Nov;37:521-534
pubmed: 30389504
Spine (Phila Pa 1976). 2004 Jul 15;29(14):1508-14
pubmed: 15247571