A comparison of BMP2 delivery by coacervate and gene therapy for promoting human muscle-derived stem cell-mediated articular cartilage repair.
Bone morphogenetic proteins 2
Cartilage repair
Coacervate
Human muscle-derived stem cells
Osteoarthritis
Soluble fms-like tyrosine kinase-1
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
26 11 2019
26 11 2019
Historique:
received:
22
05
2019
accepted:
30
09
2019
revised:
31
07
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
22
7
2020
Statut:
epublish
Résumé
Osteoarthritis and cartilage injury treatment is an unmet clinical need. Therefore, development of new approaches to treat these diseases is critically needed. Previous work in our laboratory has shown that murine muscle-derived stem cells (MDSCs) can efficiently repair articular cartilage in an osteochondral and osteoarthritis model. However, the cartilage repair capacity of human muscle-derived stem cells has not been studied which prompt this study. In this study, we tested the in vitro chondrogenesis ability of six populations of human muscle-derived stem cells (hMDSCs), before and after lenti-BMP2/GFP transduction using pellet culture and evaluated chondrogenic differentiation of via histology and Raman spectroscopy. We further compared the in vivo articular cartilage repair of hMDSCs stimulated with BMP2 delivered through coacervate sustain release technology and lenti-viral gene therapy-mediated gene delivery in a monoiodoacetate (MIA)-induced osteoarthritis (OA) model. We used microCT and histology to evaluate the cartilage repair. We observed that all hMDSCs were able to undergo chondrogenic differentiation in vitro. As expected, lenti-BMP2/GFP transduction further enhanced the chondrogenic differentiation capacities of hMDSCs, as confirmed by Alcian blue and Col2A1staining as well as Raman spectroscopy analysis. We observed through micro-CT scanning, Col2A1 staining, and histological analyses that delivery of BMP2 with coacervate could achieve a similar articular cartilage repair to that mediated by hMDSC-LBMP2/GFP. We also found that the addition of soluble fms-like tyrosine kinase-1 (sFLT-1) protein further improved the regenerative potential of hMDSCs/BMP2 delivered through the coacervate sustain release technology. Donor cells did not primarily contribute to the repaired articular cartilage since most of the repair cells are host derived as indicated by GFP staining. We conclude that the delivery of hMDSCs and BMP2 with the coacervate technology can achieve a similar cartilage repair relative to lenti-BMP2/GFP-mediated gene therapy. The use of coacervate technology to deliver BMP2/sFLT1 with hMDSCs for cartilage repair holds promise for possible clinical translation into an effective treatment modality for osteoarthritis and traumatic cartilage injury.
Sections du résumé
BACKGROUND
Osteoarthritis and cartilage injury treatment is an unmet clinical need. Therefore, development of new approaches to treat these diseases is critically needed. Previous work in our laboratory has shown that murine muscle-derived stem cells (MDSCs) can efficiently repair articular cartilage in an osteochondral and osteoarthritis model. However, the cartilage repair capacity of human muscle-derived stem cells has not been studied which prompt this study.
METHOD
In this study, we tested the in vitro chondrogenesis ability of six populations of human muscle-derived stem cells (hMDSCs), before and after lenti-BMP2/GFP transduction using pellet culture and evaluated chondrogenic differentiation of via histology and Raman spectroscopy. We further compared the in vivo articular cartilage repair of hMDSCs stimulated with BMP2 delivered through coacervate sustain release technology and lenti-viral gene therapy-mediated gene delivery in a monoiodoacetate (MIA)-induced osteoarthritis (OA) model. We used microCT and histology to evaluate the cartilage repair.
RESULTS
We observed that all hMDSCs were able to undergo chondrogenic differentiation in vitro. As expected, lenti-BMP2/GFP transduction further enhanced the chondrogenic differentiation capacities of hMDSCs, as confirmed by Alcian blue and Col2A1staining as well as Raman spectroscopy analysis. We observed through micro-CT scanning, Col2A1 staining, and histological analyses that delivery of BMP2 with coacervate could achieve a similar articular cartilage repair to that mediated by hMDSC-LBMP2/GFP. We also found that the addition of soluble fms-like tyrosine kinase-1 (sFLT-1) protein further improved the regenerative potential of hMDSCs/BMP2 delivered through the coacervate sustain release technology. Donor cells did not primarily contribute to the repaired articular cartilage since most of the repair cells are host derived as indicated by GFP staining.
CONCLUSIONS
We conclude that the delivery of hMDSCs and BMP2 with the coacervate technology can achieve a similar cartilage repair relative to lenti-BMP2/GFP-mediated gene therapy. The use of coacervate technology to deliver BMP2/sFLT1 with hMDSCs for cartilage repair holds promise for possible clinical translation into an effective treatment modality for osteoarthritis and traumatic cartilage injury.
Identifiants
pubmed: 31771623
doi: 10.1186/s13287-019-1434-3
pii: 10.1186/s13287-019-1434-3
pmc: PMC6880474
doi:
Substances chimiques
BMP2 protein, human
0
Bone Morphogenetic Protein 2
0
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
346Subventions
Organisme : NIAMS NIH HHS
ID : R21 AR066206
Pays : United States
Organisme : National Institute of Health of United States
ID : R21AR066206
Pays : International
Références
Arthritis Rheum. 2008 Dec;58(12):3809-19
pubmed: 19035511
Arthroscopy. 2016 Jan;32(1):97-109
pubmed: 26585585
Tissue Eng. 2007 Jul;13(7):1615-21
pubmed: 17518742
Biomaterials. 2012 Mar;33(7):2016-24
pubmed: 22189147
Tissue Eng Part A. 2015 Nov;21(21-22):2733-43
pubmed: 26414238
Stem Cells Transl Med. 2013 Sep;2(9):667-77
pubmed: 23884640
Osteoarthritis Cartilage. 2006 Jan;14(1):13-29
pubmed: 16242352
Hum Mol Genet. 2016 Aug 1;25(15):3216-3231
pubmed: 27354351
J Control Release. 2015 Jun 10;207:7-17
pubmed: 25836592
Cell Transplant. 2013;22(12):2393-408
pubmed: 23244588
Biomaterials. 2012 Oct;33(29):7008-18
pubmed: 22818985
Biomaterials. 2015 Dec;72:138-51
pubmed: 26370927
Nature. 1977 Dec 22-29;270(5639):725-7
pubmed: 563524
Osteoarthritis Cartilage. 2015 Mar;23(3):433-42
pubmed: 25463442
J Orthop Res. 2014 Sep;32(9):1167-74
pubmed: 24839120
Osteoarthritis Cartilage. 2016 Jul;24(7):1284-91
pubmed: 26915639
J Control Release. 2013 Mar 10;166(2):124-9
pubmed: 23154193
Image J Nurs Sch. 1990 Spring;22(1):8-13
pubmed: 2180804
Arthritis Rheum. 2009 Jan;60(1):155-65
pubmed: 19116905
J Orthop Surg Res. 2017 Mar 9;12(1):39
pubmed: 28279182
Am J Sports Med. 2019 Jun;47(7):1621-1628
pubmed: 31095402
J Control Release. 2011 Mar 10;150(2):157-63
pubmed: 21118705
Mol Ther Methods Clin Dev. 2016 Nov 30;3:16065
pubmed: 27990446
Stem Cell Res Ther. 2019 Mar 5;10(1):72
pubmed: 30837004
Arthritis Rheum. 2006 Feb;54(2):433-42
pubmed: 16447218
Arthritis Rheum. 2009 May;60(5):1390-405
pubmed: 19404941
Wound Repair Regen. 2015 Jul-Aug;23(4):591-600
pubmed: 26032846
J Tissue Eng Regen Med. 2018 Jun;12(6):1327-1338
pubmed: 29522657
J Cell Biol. 1994 Jun;125(6):1275-87
pubmed: 8207057
Acta Biomater. 2013 Jul;9(7):7276-88
pubmed: 23535234
Mol Ther. 2014 Jan;22(1):186-95
pubmed: 23851345
Cartilage. 2018 Oct;9(4):410-416
pubmed: 28608754
J Bone Joint Surg Am. 2016 Jan 6;98(1):23-34
pubmed: 26738900
Biomaterials. 2013 Feb;34(6):1747-56
pubmed: 23211448
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13444-9
pubmed: 21808045
Biomaterials. 2017 Apr;124:65-77
pubmed: 28188996
PLoS One. 2013 May 14;8(5):e63075
pubmed: 23690982
Stem Cell Res Ther. 2018 Nov 21;9(1):316
pubmed: 30463597
FASEB J. 2014 Aug;28(8):3792-809
pubmed: 24843069
Proc Natl Acad Sci U S A. 1968 Oct;61(2):477-83
pubmed: 5245982
Stem Cell Res Ther. 2017 Nov 15;8(1):264
pubmed: 29141683
Stem Cell Res Ther. 2019 May 21;10(1):143
pubmed: 31113476
Methods Mol Biol. 2013;976:53-65
pubmed: 23400434
J Control Release. 2017 May 10;253:73-81
pubmed: 28315407
Biomaterials. 2009 May;30(14):2683-93
pubmed: 19217157