Structured three‐dimensional co‐culture of mesenchymal stem cells with meniscus cells promotes meniscal phenotype without hypertrophy

Abstract

Menisci play a crucial role in weight distribution, load bearing, shock absorption, lubrication, and nutrition of articular cartilage within the knee joint. Damage to the meniscus typically does not heal spontaneously due to its partial avascular nature. Partial or complete meniscectomy is a common clinical treatment of the defective meniscus. However, this procedure ultimately leads to osteoarthritis due to increased mechanical stress to the articular cartilage. Meniscus tissue engineering offers a promising solution for partial or complete meniscus deficiency. Mesenchymal stem cells (MSC) have the potential to differentiate into meniscal fibrochondrocyte as well as deliver trophic effects to the differentiated cells. This study tested the feasibility of using MSC co‐cultured with mature meniscal cells (MC) for meniscus tissue engineering. Structured cell pellets were created using MC and MSC at varying ratios (100:0, 75:25, 50:50, 25:75, and 0:100) and cultured with or without transforming growth factor‐beta 3 supplemented chondrogenic media for 21 days. The meniscal and hypertrophic gene expression, gross appearance and structure of the pellets, meniscus extracellular matrix (ECM), histology and immunohistochemistry of proteoglycan and collagen were evaluated. Co‐culture of MC with MSC at 75:25 demonstrated highest levels of collagen type I and glycosaminoglycans (GAG) production, as well as the lowest levels of hypertrophic genes, such as COL10A1 and MMP13. All co‐culture conditions showed better meniscus ECM production and hypertrophic inhibition as compared to MSC culture alone. The collagen fiber bundles observed in the co‐cultures are important to produce heterogenic ECM structure of meniscus. In conclusion, co‐culturing MC and MSC is a feasible and efficient approach to engineer meniscus tissue with enhanced ECM production without hypertrophy. Biotechnol. Bioeng. 2012;109: 2369–2380. © 2012 Wiley Periodicals, Inc.

Inkjet‐bioprinted acrylated peptides and PEG hydrogel with human mesenchymal stem cells promote robust bone and cartilage formation with minimal printhead clogging

“…In contrast, the same hypertrophic expression in PEG-Peptide scaffold was substantially lower than that in PEG group. This strongly inhibited hypertrophy was striking comparing to previous hMSCs chondrogenic studies using TGFβ [12], in which MSC hypertrophy persists as a consistent hallmark despite strong chondrogenic effect delivered by TGFβ. It suggests that the persistent hMSCs hypertrophy in chondrogenic differentiation could be significantly alleviated by an uncomplicated bioprinted PEG-Peptide system.…”

“…Cells were expanded as previously reported [12,15]. Fifth passage (P5) hMSCs were used in this study.…”

Stem cell delivery in tissue-specific hydrogel enabled meniscal repair in an orthotopic rat model

“…Previous studies have found that the meniscus itself contains a subpopulation of multipotential cells [23,30,36,64], which can be utilized to regenerate tissue. Moreover, the combination of MSCs with native meniscal cells is known to prevent MSC hypertrophy [65,66]. Future work will focus on the interactions between exogenously delivered MSCs and endogenous meniscal cells under the direction of meniscus tissue-specific cues present in mECM hydrogel.…”

Human Cartilage Tissue Fabrication Using Three-dimensional Inkjet Printing Technology

“…With digital control and high throughput printheads cells, scaffolds, and growth factors can be precisely deposited to the desired twodimensional (2D) and three-dimensional (3D) positions rapidly. Many successful applications have been achieved using this technology in tissue engineering and regenerative medicine [1][2][3][4][5][6][7][8][9] . In this paper, a bioprinting platform was established with a modified Hewlett-Packard (HP) Deskjet 500 thermal inkjet printer and a simultaneous photopolymerization system.…”