title: Dual release of dexamethasone and TGF-β3 from polymeric microspheres for stem cell matrix accumulation in a rat disc degeneration model.
abstract: Low back pain is frequently caused by nucleus pulposus (NP) degeneration. Tissue engineering is a powerful therapeutic strategy which could restore the normal biomechanical motion of the human spine. Previously we reported that a new nanostructured three-dimensional poly(lactide-co-glycolide) (PLGA) microsphere, which is loaded with dexamethasone and growth factor embedded heparin/poly(l-lysine) nanoparticles via a layer-by-layer system, was an effective cell carrier in vitro for NP tissue engineering. This study aimed to investigate whether the implantation of adipose-derived stem cell (ADSC)-seeded PLGA microspheres into the rat intervertebral disc could regenerate the degenerated disc. Changes in disc height by plain radiograph, T2-weighted signal intensity in magnetic resonance imaging (MRI), histology, immunohistochemistry and matrix-associated gene expression were evaluated in normal controls (NCs) (without operations), a degeneration control (DC) group (with needle puncture, injected only with Dulbecco's modified Eagle's medium), a PLGA microspheres (PMs) treatment group (with needle puncture, PLGA microspheres only injection), and PLGA microspheres loaded with ADSCs treatment (PMA) group (with needle puncture, PLGA microspheres loaded with ADSC injection) for a 24-week period. The results showed that at 24 weeks post-transplantation, the PM and PMA groups regained disc height values of ∼63% and 76% and MRI signal intensities of ∼47% and 76%, respectively, compared to the NC group. Biochemistry, immunohistochemistry and gene expression analysis also indicated the restoration of proteoglycan accumulation in the discs of the PM and PMA groups. However, there was almost no restoration of proteoglycan accumulation in the discs of the DC group compared with the PM and PMA groups. Taken together, these data suggest that ADSC-seeded PLGA microspheres could partly regenerate the degenerated disc in vivo after implantation into the rat degenerative intervertebral disc.
authors: Department of Orthopedic Surgery, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, Zhejiang, People's Republic of China.
authors: Cheng-zhen
authors: CZ
authors: Liang
authors: Hao
authors: H
authors: Li
authors: Yi-qing
authors: YQ
authors: Tao
authors: Li-hua
authors: LH
authors: Peng
authors: Jian-qing
authors: JQ
authors: Gao
authors: Jing-jun
authors: JJ
authors: Wu
authors: Fang-cai
authors: FC
authors: Li
authors: Jian-ming
authors: JM
authors: Hua
authors: Qi-xin
authors: QX
authors: Chen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D057446:Hydrodynamics; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000000981:diagnostic imaging / Q000473:pathology* / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008863:Microspheres; D053758:Nanoparticles / Q000648:ultrastructure; D011098:Polyglactin 910 / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D006025:Glycosaminoglycans; D053782:Transforming Growth Factor beta3; D014867:Water; D011098:Polyglactin 910; D003907:Dexamethasone; D006493:Heparin; D006909:Hydroxyproline
keywords: Adipose-derived stem cell; Layer-by-layer approach; Nucleus pulposus tissue engineering; PLGA microsphere; Transforming growth factor β3