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

Wayne Yuk Wai Lee,Liming Bian,Yuanfeng Chen,Gene Chi Wai Man,Sien Lin,Qian Feng,Liao Cui,Bo Wei,Liangliang Xu,Bin Wang,Gang Li,Xiaohua Jiang

doi:10.1186/s13287-017-0672-5

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.

Highlights

Mesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration
Manipulated mesenchymal stem cell (M-MSC) exhibited higher chondrogenic capacity compared with untreated MSCs (Fig. 2a and c) which was consistent with our recent report [19]
Results illustrated that large amounts of GAG and Col Type collagen (II), a much larger pellet size (P < 0.001), and upregulated expressions of Col2a1 (P < 0.01), Acan (P > 0.05), and Sox9 (P < 0.05) were found in the M-MSC pellets compared with untreated MSCs (Fig. 2a and b)

Summary

Introduction

Mesenchymal stem cells (MSCs) hold promising translational potential in cartilage regeneration. 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. Articular cartilage damage resulting from a sudden injury or wear and tear could predispose to development of traumatic osteoarthritis (OA). Conventional surgical procedures including arthroscopic debridement [3], bone marrow stimulation [4, 5], and autograft or allograft mosaicplasty [6] are used to stimulate cartilage repair, but none of these treatments can prevent the affected cartilage from progressive destruction [7]

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