title: Retinoic acid and human olfactory ensheathing cells cooperate to promote neural induction from human bone marrow stromal stem cells.
abstract: The generation of induced neuronal cells from human bone marrow stromal stem cells (hBMSCs) provides new avenues for basic research and potential transplantation therapies for nerve injury and neurological disorders. However, clinical application must seriously consider the risk of tumor formation by hBMSCs, neural differentiation efficiency and biofunctions resembling neurons. Here, we co-cultured hBMSCs exposed to retinoic acid (RA) with human olfactory ensheathing cells (hOECs) to stimulate its differentiation into neural cells, and found that hBMSCs following 1 and 2 weeks of stimulation promptly lost their immunophenotypical profiles, and gradually acquired neural cell characteristics, as shown by a remarkable up-regulation of expression of neural-specific markers (Tuj-1, GFAP and Galc) and down-regulation of typical hBMSCs markers (CD44 and CD90), as well as a rapid morphological change. Concomitantly, in addition to a drastic decrease in the number of BrdU incorporated cells, there was a more elevated synapse formation (a hallmark for functional neurons) in the differentiated hBMSCs. Compared with OECs alone, this specific combination of RA and hOECs was significantly potentiated neuronal differentiation of hBMSCs. The results suggest that RA can enhance and orchestrate hOECs to neural differentiation of hBMSCs. Therefore, these findings may provide an alternative strategy for the repair of traumatic nerve injury and neurological diseases with application of the optimal combination of RA and OECs for neuronal differentiation of hBMSCs.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Xie
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Zuping
authors.initials: Z
authors.lastname: He
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Gao
authors.forename: Da-Hai
authors.initials: DH
authors.lastname: Hu
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
mesh_terms: D000943:Antigens, Differentiation / Q000032:analysis; D001253:Astrocytes / Q000166:cytology; D019070:Cell Lineage; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D018920:Coculture Techniques; D005698:Galactosylceramidase / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009432:Neural Crest / Q000166:cytology; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology; D009830:Olfactory Bulb / Q000166:cytology*; D009831:Olfactory Mucosa / Q000166:cytology*; D009836:Oligodendroglia / Q000166:cytology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*; D014404:Tubulin / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000943:Antigens, Differentiation; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C498585:TUBB3 protein, human; D014404:Tubulin; D014212:Tretinoin; D005698:Galactosylceramidase