Co-culture of hWJMSCs and pACs in double biomimetic ACECM oriented scaffold enhances mechanical properties and accelerates articular cartilage regeneration in a caprine model.
Acellular cartilage extracellular matrix-oriented scaffold
Co-culture system
Human umbilical cord Wharton’s jelly-derived mesenchymal stem cell
Primary cartilage cell
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:
19 05 2020
19 05 2020
Historique:
received:
28
01
2020
accepted:
06
04
2020
revised:
20
03
2020
entrez:
21
5
2020
pubmed:
21
5
2020
medline:
22
6
2021
Statut:
epublish
Résumé
The dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton's jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage. A double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area. Relative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young's modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system. The structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.
Sections du résumé
BACKGROUND
The dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton's jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage.
METHODS
A double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area.
RESULTS
Relative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young's modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system.
CONCLUSION
The structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.
Identifiants
pubmed: 32430067
doi: 10.1186/s13287-020-01670-2
pii: 10.1186/s13287-020-01670-2
pmc: PMC7238567
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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