Neonatal desensitization supports long-term survival and functional integration of human embryonic stem cell-derived mesenchymal stem cells in rat joint cartilage without immunosuppression.
Immunological response hampers the investigation of human embryonic stem cells (hESCs) or their derivates for tissue regeneration in vivo. Immunosuppression is often used after surgery, but exhibits side effects of significant weight loss and allows only short-term observation. The purpose of this study was to investigate whether neonatal desensitization supports relative long-term survival of hESC-derived mesenchymal stem cells (hESC-MSCs) and promotes cartilage regeneration. hESC-MSCs were injected on the day of birth in rats. Six weeks after neonatal injection, a full-thickness cylindrical cartilage defect was created and transplanted with a hESC-MSC-seeded collagen bilayer scaffold (group d+s+c) or a collagen bilayer scaffold (group d+s). Rats without neonatal injection were transplanted with the hESC-MSC-seeded collagen bilayer scaffold to serve as controls (group s+c). Cartilage regeneration was evaluated by histological analysis, immunohistochemical staining, and biomechanical test. The role of hESC-MSCs in cartilage regeneration was analyzed by CD4 immunostaining, cell death detection, and visualization of human cells in regenerated tissues. hESC-MSCs expressed CD105, CD73, CD90, CD29, and CD44, but not CD45 and CD34, and possessed trilineage differentiation potential. Group d+s+c exhibited greater International Cartilage Repair Society (ICRS) scores than group d+s or group s+c. Abundant collagen type II and improved mechanical properties were detected in group d+s+c. There were less CD4+ inflammatory cell infiltration and cell death at week 1, and hESC-MSCs were found to survive as long as 8 weeks after transplantation in group d+s+c. Our study suggests that neonatal desensitization before transplantation may be an efficient way to develop a powerful tool for preclinical study of human cell-based therapies in animal models.
Center for Stem Cell and Tissue Engineering, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Shufang
S
Zhang
Yang Zi
YZ
Jiang
Wei
W
Zhang
Longkun
L
Chen
Tong
T
Tong
Wanlu
W
Liu
Qin
Q
Mu
Hua
H
Liu
Junfeng
J
Ji
Hong Wei
HW
Ouyang
Xiaohui
X
Zou
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D001696:Biomechanical Phenomena; D002358:Cartilage, Articular / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D024043:Collagen Type II / Q000378:metabolism; D003888:Desensitization, Immunologic; D053595:Embryonic Stem Cells / Q000502:physiology*; D006087:Graft vs Host Reaction; D006801:Humans; D007165:Immunosuppression Therapy; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D012038:Regeneration; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous
D015703:Antigens, CD; D024043:Collagen Type II