title: Differentiation of human adipose-derived stem cells into neuron-like cells which are compatible with photocurable three-dimensional scaffolds.
abstract: Multipotent human adipose-derived stromal/stem cells (hADSCs) hold a great promise for cell-based therapy for many devastating human diseases, such as spinal cord injury and stroke. If exogenous hADSCs can be cultured in a three-dimensional (3D) scaffold with effective proliferation and differentiation capacity, it will better mimic the in vivo environment, which will have profound impact on the therapeutic application of hADSCs. In this study, a group of elastic-dominant, porous bioscaffolds from photocurable chitosan and gelatin were fabricated and proven to be biocompatible with both hADSCs and hADSC-derived neuron-like cells (hADSC-NLCs) in vitro. The identity of harvested hADSCs was confirmed by their positive immunostaining of mesenchymal stem cell surface markers, CD29, CD44, and CD105, and also positive expression of stem markers, Sox-2, Oct-4, c-Myc, Nanog, and Klf4. Their multipotency was further confirmed by trilineage differentiation of hADSCs toward adipocyte, osteoblast, and chondrocyte. It was found that hADSCs could be conditioned to differentiate into neurons in vitro as determined by immunostaining the markers of Tuj1, MAP2, NeuN, and Synapsin. The hADSCs and hADSC-NLCs were proven to be biocompatible with 3D scaffold, which actually facilitated the proliferation and differentiation of hADSCs in vitro, by MTT assay and their neuronal gene expression profiling. Moreover, hADSC-NLCs, which were mixed with 3D scaffold and transplanted into traumatic brain injury mouse model, survived in vivo and led to the better repair of the damaged brain area. The immunohistochemical studies revealed that 3D scaffold indeed improved the viability of transplanted cells, their ability to incorporate into the in vivo neural circuit, and their capacity for tissue repair. This study indicates that hADSCs would have great therapeutic application potential as seeding cells for in vivo transplantation to treat various neurological diseases when co-applied with porous chitosan/gelatin bioscaffolds.
authors.affiliation: 1 East Hospital, Tongji University School of Medicine , Shanghai, P.R. China .
authors.forename: Shane
authors.initials: S
authors.lastname: Gao
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.forename: Yuxi
authors.initials: Y
authors.lastname: Sun
authors.forename: Yilei
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhichong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Danjing
authors.initials: D
authors.lastname: Yang
authors.forename: Xianli
authors.initials: X
authors.lastname: Wang
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.forename: Limei
authors.initials: L
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Ke
authors.initials: K
authors.lastname: Ning
authors.forename: Xu
authors.initials: X
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology; D001930:Brain Injuries / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects*; D019070:Cell Lineage / Q000187:drug effects / Q000528:radiation effects; D048430:Cell Shape / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology; D004195:Disease Models, Animal; D005780:Gelatin / Q000494:pharmacology; D006801:Humans; D000090062:Kruppel-Like Factor 4; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D055668:Photochemical Processes; D017550:Spectroscopy, Fourier Transform Infrared; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry*; D014157:Transcription Factors / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D015703:Antigens, CD; D001672:Biocompatible Materials; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D014157:Transcription Factors; D005780:Gelatin; D048271:Chitosan