Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model.
: The regeneration of tissue-engineered cartilage in an immunocompetent environment usually fails due to severe inflammation induced by the scaffold and their degradation products. In the present study, we compared the tissue remodeling and the inflammatory responses of engineered cartilage constructed with bone marrow mesenchymal stem cells (BMSCs), chondrocytes, or both and scaffold group in pigs. The cartilage-forming capacity of the constructs in vitro and in vivo was evaluated by histological, biochemical, and biomechanical analyses, and the inflammatory response was investigated by quantitative analysis of foreign body giant cells and macrophages. Our data revealed that BMSC-based engineered cartilage suppressed in vivo inflammation through the alteration of macrophage phenotype, resulting in better tissue survival compared with those regenerated with chondrocytes alone or in combination with BMSCs. To further confirm the macrophage phenotype, an in vitro coculture system established by engineered cartilage and macrophages was studied using immunofluorescence, enzyme-linked immunosorbent assay, and gene expression analysis. The results demonstrated that BMSC-based engineered cartilage promoted M2 polarization of macrophages with anti-inflammatory phenotypes including the upregulation of CD206, increased IL-10 synthesis, decreased IL-1β secretion, and alterations in gene expression indicative of M1 to M2 transition. It was suggested that BMSC-seeded constructs have the potential to ameliorate scaffold-induced inflammation and improve cartilaginous tissue regeneration through M2 polarization of macrophages.



Finding a strategy that can prevent scaffold-induced inflammation is of utmost importance for the regeneration of tissue-engineered cartilage in an immunocompetent environment. This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting in better tissue survival in a pig model. Additionally, the effect of BMSC-based cartilage on the phenotype conversion of macrophages was further studied through an in vitro coculture system. This study could provide further support for the regeneration of cartilage engineering in immunocompetent animal models and provide new insight into the interaction of tissue-engineered cartilage and macrophages.
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Jinping
J
Ding
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Bo
B
Chen
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Tao
T
Lv
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Xia
X
Liu
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Xin
X
Fu
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Qian
Q
Wang
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Li
L
Yan
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ningkang1983@yahoo.com yilincao@yahoo.com xiaoran@pumc.edu.cn.
Ning
N
Kang
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ningkang1983@yahoo.com yilincao@yahoo.com xiaoran@pumc.edu.cn.
Yilin
Y
Cao
Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China ningkang1983@yahoo.com yilincao@yahoo.com xiaoran@pumc.edu.cn.
Ran
R
Xiao
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002356:Cartilage / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D020219:Chondrogenesis; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D055119:Elastic Modulus; D005549:Foreign-Body Reaction / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D006025:Glycosaminoglycans / Q000378:metabolism; D006085:Graft Survival; D019344:Lactic Acid / Q000737:chemistry* / Q000633:toxicity; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000633:toxicity; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013552:Swine; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
D006025:Glycosaminoglycans; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen
Bone marrow mesenchymal stem cells; Cartilage tissue engineering; Immunocompetent; Macrophage polarization; Scaffold-induced inflammation