Gene expression modulation in TGF-β3-mediated rabbit bone marrow stem cells using electrospun scaffolds of various stiffness.
Tissue engineering has recently evolved into a promising approach for annulus fibrosus (AF) regeneration. However, selection of an ideal cell source, which can be readily differentiated into AF cells of various regions, remains challenging because of the heterogeneity of AF tissue. In this study, we set out to explore the feasibility of using transforming growth factor-β3-mediated bone marrow stem cells (tBMSCs) for AF tissue engineering. Since the differentiation of stem cells significantly relies on the stiffness of substrate, we fabricated nanofibrous scaffolds from a series of biodegradable poly(ether carbonate urethane)-urea (PECUU) materials whose elastic modulus approximated that of native AF tissue. We cultured tBMSCs on PECUU scaffolds and compared their gene expression profile to AF-derived stem cells (AFSCs), the newly identified AF tissue-specific stem cells. As predicted, the expression of collagen-I in both tBMSCs and AFSCs increased with scaffold stiffness, whereas the expression of collagen-II and aggrecan genes showed an opposite trend. Interestingly, the expression of collagen-I, collagen-II and aggrecan genes in tBMSCs on PECUU scaffolds were consistently higher than those in AFSCs regardless of scaffold stiffness. In addition, the cell traction forces (CTFs) of both tBMSCs and AFSCs gradually decreased with scaffold stiffness, which is similar to the CTF change of cells from inner to outer regions of native AF tissue. Together, findings from this study indicate that tBMSCs had strong tendency to differentiate into various types of AF cells and presented gene expression profiles similar to AFSCs, thereby establishing a rationale for the use of tBMSCs in AF tissue engineering.
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.|Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China.
Qianping
Q
Guo
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Chen
C
Liu
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Jun
J
Li
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.|Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China.
Caihong
C
Zhu
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.|Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China.
Huilin
H
Yang
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.|Orthopedic Institute, Soochow University, Suzhou, Jiangsu, China.
Bin
B
Li
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007403:Intervertebral Disc / Q000166:cytology; D008969:Molecular Sequence Data; D011817:Rabbits; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*; D014520:Urethane / Q000737:chemistry
D053782:Transforming Growth Factor beta3; D014520:Urethane; D003094:Collagen
TGF-β3 treatment; annulus fibrosus-derived stem cells; bone marrow stem cells; electrospun scaffolds; gene expression; stiffness