Mesenchymal stromal cells for articular cartilage repair: preclinical studies

Objectives Functions of mesenchymal stem/stromal cells (MSCs) are affected by patient-dependent factors such as age and health condition. To tackle this problem, we used the cellular reprogramming technique to epigenetically alter human MSCs derived from the synovial fluid of joints with osteoarthritis (OA) to explore the potential of reprogrammed MSCs for repairing articular cartilage. Materials and Methods MSCs isolated from the synovial fluid of three patients’ OA knees (Pa-MSCs) were reprogrammed through overexpression of pluripotency factors and then induced for differentiation to establish reprogrammed MSC (Re-MSC) lines. We compared the in vitro growth characteristics, chondrogenesis for articular cartilage chondrocytes, and immunomodulatory capacity. We also evaluated the capability of Re-MSCs to repair articular cartilage damage in an animal model with spontaneous OA. Results Our results showed that Re-MSCs increased the in vitro proliferative capacity and improved chondrogenic differentiation toward articular cartilage-like chondrocyte phenotypes with increased THBS4 and SIX1 and decreased ALPL and COL10A1, compared to Pa-MSCs. In addition, Re-MSC-derived chondrocytes expressing elevated COL2A and COL2B were more mature than parental cell-derived ones. The enhancement in chondrogenesis of Re-MSC involves the upregulation of sonic hedgehog signaling. Moreover, Re-MSCs improved the repair of articular cartilage in an animal model of spontaneous OA. Conclusions Epigenetic reprogramming promotes MSCs harvested from OA patients to increase phenotypic characteristics and gain robust functions. In addition, Re-MSCs acquire an enhanced potential for articular cartilage repair. Our study here demonstrates that the reprogramming strategy provides a potential solution to the challenge of variation in MSC quality.

Download Full-text

A Comparison of the Capacity of Mesenchymal Stromal Cells for Cartilage Regeneration Depending on Collagen-Based Injectable Biomimetic Scaffold Type

Life ◽

10.3390/life11080756 ◽

2021 ◽

Vol 11 (8) ◽

pp. 756

Author(s):

Victor I. Sevastianov ◽

Yulia B. Basok ◽

Ludmila A. Kirsanova ◽

Alexey M. Grigoriev ◽

Alexandra D. Kirillova ◽

...

Keyword(s):

Articular Cartilage ◽

Experimental Model ◽

Mesenchymal Stromal Cells ◽

Cartilage Repair ◽

Stromal Cells ◽

Cartilage Damage ◽

Cartilage Regeneration ◽

Human Adipose Tissue ◽

Rabbit Knee

Mesenchymal stromal cells (MSCs) have shown a high potential for cartilage repair. Collagen-based scaffolds are used to deliver and retain cells at the site of cartilage damage. The aim of the work was a comparative analysis of the capacity of the MSCs from human adipose tissue to differentiate into chondrocytes in vitro and to stimulate the regeneration of articular cartilage in an experimental model of rabbit knee osteoarthrosis when cultured on microheterogenic collagen-based hydrogel (MCH) and the microparticles of decellularized porcine articular cartilage (DPC). The morphology of samples was evaluated using scanning electron microscopy and histological staining methods. On the surface of the DPC, the cells were distributed more uniformly than on the MCH surface. On day 28, the cells cultured on the DPC produced glycosaminoglycans more intensely compared to the MCH with the synthesis of collagen type II. However, in the experimental model of osteoarthrosis, the stimulation of the cartilage regeneration was more effective when the MSCs were administered to the MCH carrier. The present study demonstrates the way to regulate the action of the MSCs in the area of cartilage regeneration: the MCH is more conducive to stimulating cartilage repair by the MSCs, while the DPC is an inducer for a formation of a cartilage-like tissue by the MSCs in vitro.

Download Full-text

A Comparison of the Capacity of Mesenchymal Stromal Cells for Cartilage Regeneration Depending on Collagen-Based Injectable Biomimetic Scaffold Type

10.20944/preprints202106.0739.v1 ◽

2021 ◽

Author(s):

Victor Sevastianov ◽

Yulia Basok ◽

Ludmila Kirsanova ◽

Alexey Grigoriev ◽

Alexandra Kirillova ◽

...

Keyword(s):

Articular Cartilage ◽

Experimental Model ◽

Mesenchymal Stromal Cells ◽

Cartilage Repair ◽

Stromal Cells ◽

Cartilage Damage ◽

Cartilage Regeneration ◽

Human Adipose Tissue ◽

Rabbit Knee

Mesenchymal stromal cells (MSCs) have shown a high potential for cartilage repair. Collagen-based scaffolds are used to deliver and retain cells at the site of cartilage damage. The aim of the work was a comparative analysis of the capacity of the MSCs from human adipose tissue to differentiate into chondrocytes in vitro and to stimulate the regeneration of articular cartilage in an experimental model of rabbit knee osteoarthrosis when cultured on microheterogenic collagen-based hydrogel (МCH) and the microparticles of decellularized porcine articular cartilage (DPC). The morphology of samples was evaluated using scanning electron microscopy and histological staining methods. On the surface of the DPC, the cells were distributed more uniformly than on the MCH surface. On day 28, the cells cultured on the DPC produced glycosaminoglycans more intensely compared to the MCH with the synthesis of collagen type II. However, in the experimental model of osteoarthrosis, the stimulation of the cartilage regeneration was more effective when the MSCs were administered to the MCH carrier. The present study demonstrates the way to regulate the action of the MSCs in the area of cartilage regeneration: the MCH is more conducive to stimulating cartilage repair by the MSCs, while the DPC is an inducer for a formation of a cartilage-like tissue by the MSCs in vitro.

Download Full-text

PVA‐Based Hydrogels: Promising Candidates for Articular Cartilage Repair

Macromolecular Bioscience ◽

10.1002/mabi.202100147 ◽

2021 ◽

pp. 2100147

Author(s):

Yuru Chen ◽

Jian Song ◽

Song Wang ◽

Weiqiang Liu

Keyword(s):

Articular Cartilage ◽

Cartilage Repair ◽

Articular Cartilage Repair

Download Full-text

Human Mesenchymal Stromal Cells Enhance Cartilage Healing in a Murine Joint Surface Injury Model

Cells ◽

10.3390/cells10081999 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1999

Author(s):

Jade Perry ◽

Anke J. Roelofs ◽

Claire Mennan ◽

Helen S. McCarthy ◽

Alison Richmond ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Cartilage Repair ◽

Stromal Cells ◽

Fluorescent Protein ◽

Joint Surface ◽

Human Umbilical Cord ◽

Repair Tissue ◽

Adult Mice ◽

Chondral Defects ◽

Repair Mechanisms

Human umbilical cord (hUC)- or bone marrow (hBM)-derived mesenchymal stromal cells (MSCs) were evaluated as an allogeneic source of cells for cartilage repair. We aimed to determine if they could enhance healing of chondral defects with or without the recruitment of endogenous cells. hMSCs were applied into a focal joint surface injury in knees of adult mice expressing tdTomato fluorescent protein in cells descending from Gdf5-expressing embryonic joint interzone cells. Three experimental groups were used: (i) hUC-MSCs, (ii) hBM-MSCs and (iii) PBS (vehicle) without cells. Cartilage repair was assessed after 8 weeks and tdTomato-expressing cells were detected by immunostaining. Plasma levels of pro-inflammatory mediators and other markers were measured by electrochemiluminescence. Both hUC-MSC (n = 14, p = 0.009) and hBM-MSC (n = 13, p = 0.006) treatment groups had significantly improved cartilage repair compared to controls (n = 18). While hMSCs were not detectable in the repair tissue at 8 weeks post-implantation, increased endogenous Gdf5-lineage cells were detected in repair tissue of hUC-MSC-treated mice. This xenogeneic study indicates that hMSCs enhance intrinsic cartilage repair mechanisms in mice. Hence, hMSCs, particularly the more proliferative hUC-MSCs, could represent an attractive allogeneic cell population for treating patients with chondral defects and perhaps prevent the onset and progression of osteoarthritis.

Download Full-text