Synergistic effects on mesenchymal stem cell-based cartilage regeneration by chondrogenic preconditioning and mechanical stimulation

Abstract

BackgroundMesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration. However, the efficacy of MSC-based tissue engineering is not satisfactory in the treatment of cartilage defect because of the inevitable cellular functional changes during ex vivo cell expansion. How to maintain the chondrogenic capacity of MSCs to improve their therapeutic outcomes remains an outstanding question.MethodsBone marrow-derived MSCs were firstly primed in chondrogenic induction medium which was then replaced with normal growth medium to attain the manipulated cells (M-MSCs). Methacrylated hyaluronic acid (MeHA) was synthesized as a scaffold to encapsulate the cells. The MSC- or M-MSC-laden constructs were treated with dynamic compressive loading (DL) in a bioreactor or with free loading (FL) for 14 days. Afterwards, the constructs were implanted in nude mice or rat models of osteochondral defects to test their efficiency in cartilage regeneration or repair.ResultsData showed that the resulting M-MSCs exhibited superior chondrogenic differentiation potential and survivability compared with untreated MSCs. More importantly, we found that DL significantly promoted neocartilage formation in the MeHA hydrogel encapsulated with M-MSCs after 30 days of implantation in nude mice. Furthermore, the constructs laden with M-MSCs after DL for 14 days significantly enhanced cartilage healing in a rat model of osteochondral defect.ConclusionsFindings from this study highlight the importance of maintaining chondrogenic potential of MSCs by in-vitro chondrogenic preconditioning and a synergistic effect of mechanical stimulation in cartilage engineering, which may shed light on the stem cell-based tissue engineering for cartilage repair.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0672-5) contains supplementary material, which is available to authorized users.

Recent Advances in Photo-Crosslinkable Hydrogels for Biomedical Applications

“…MeHA hydrogels have also been used to generate tissue engineered cartilage- and bone-like tissue constructs for cartilage and bone regeneration, respectively [104,106]. To further improve biofunctionality of MeHA hydrogel, incorporating other organic or inorganic components into it can enhance its mechanical and chemical properties.…”

“…Subsequently, the pre-polymer solution is dialyzed using a dialysis tubing with MW cut-offs that range from 6 to 8kDa for 23days to remove all the MA byproducts and unreacted MA [98,104]. Finally, the MeHA pre-polymers are produced by freeze-drying the dialyzed solution.…”

The effects of dynamic compressive loading on human mesenchymal stem cell osteogenesis in the stiff layer of a bilayer hydrogel

“…The dynamic mechanical loading environment is also important to consider in osteochondral tissue engineering. Current efforts place a large emphasis on understanding the effects of dynamic loading on the chondral layer with a few studies investigating its effects on the bone layer (Goldman & Barabino, ; S. Lin et al, ; Scholtes et al, ; Steinmetz et al, ). However, the bone layer will also experience dynamic loads, which can result in a range of mechanical responses that include strain, stress, fluid flow, and hydrostatic pressure.…”

“…The dynamic mechanical loading environment is also important to consider in osteochondral tissue engineering. Current efforts place a large emphasis on understanding the effects of dynamic loading on the chondral layer with a few studies investigating its effects on the bone layer (Goldman & Barabino, 2016;S. Lin et al, 2017;Scholtes et al, 2018;Steinmetz et al, 2015).…”

Optimizing growth media for <italic>in vitro</italic> expansion of human bone marrow-derived mesenchymal stem cells

“…18 The capability of MSCs to differentiate into multiple skeletal cell lineages under specific in vitro and in vivo conditions provides the potential for their clinical applications for repairing, bone, cartilage and joint damage by autologous stem cell transplantation or genetic tissue engineering. 15,[21][22][23][24][25]68 One of the challenges in the cell and gene therapy uses of hMSCs for a wide range of human conditions is to quickly obtain an adequate number of cells and meanwhile maintain their suitable differentiation potential to achieve therapeutic outcomes. Many in vivo and in vitro factors influence monolayer expansion to achieve a clinically relevant number of hMSCs, including the clinical attributes of subjects from whom the hMSCs were obtained, e.g., age, 2,61 serum PTH and vitamin D levels, 19 Chronic Kidney Disease, 61,34 exercises 27 and chronic ethanol intake 28 etc.…”