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

Methods
Bone 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.

Results
Data 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.

Conclusions
Findings 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.
Acceptance Date13/09/2017
All Author(s) ListSien Lin, Wayne Yuk Wai Lee, Qian Feng, Liangliang Xu, Bin Wang, Gene Chi Wai Man, Yuanfeng Chen, Xiaohua Jiang, Liming Bian, Liao Cui, Bo Wei, Gang Li
Journal nameStem Cell Research and Therapy
Year2017
Month10
Day3
Volume Number8
PublisherBioMed Central
Pages221
ISSN1757-6512
LanguagesEnglish-United States
KeywordsTissue engineering, Mesenchymal stem cells, Chondrogenesis, Mechanotransduction, Cartilage diseases

Last updated on 2020-17-09 at 03:49