Abstract
Neural stem cells (NSCs) can be isolated from nervous tissues or derived from embryonic stem cells. However, their procurement for clinical applications is limited, and there is a need for alternative types of cell that have NSCs properties. In the present study, the differentiation potential of rat adipose-derived stem cells (ADSCs) was evaluated by infecting these cells with a lentiviral vector-encoding green fluorescent protein (GFP). ADSCs transduced with lentivirus were able to generate NSC-like cells, without any effects on their growth, phenotype, and normal differentiation potential. NSC-like cells derived from ADSCs formed neurospheres and expressed high levels of the neural progenitor marker nestin. In the absence of selected growth factors, these neurospheres differentiated into neurons expressing NeuN and MAP2 and GFAP-expressing glia, as determined by immunocytochemistry, Western blotting, and quantitative real-time polymerase chain reaction. These results demonstrate that ADSCs can be induced to generate neurospheres that have NSC-like properties and may thus constitute a potential source of cells in stem cell therapy for neurological disorders.
Similar content being viewed by others
References
Zavan B, Vindigni V, Gardin C, D'Avella D, Della PA, Abatangelo G, Cortivo R (2010) Neural potential of adipose stem cells. Discov Med 10:37
Galli R, Gritti A, Bonfanti L, Vescovi AL (2003) Neural stem cells: an overview. Circ Res 92:598
Zhang HT, Cheng HY, Cai YQ, Ma X, Liu WP, Yan ZJ, Jiang XD, Xu RX (2009) Comparison of adult neurospheres derived from different origins for treatment of rat spinal cord injury. Neurosci Lett 458:116
Gage FH (2000) Mammalian neural stem cells. Science 287:1433
Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279
Vieira NM, Brandalise V, Zucconi E, Secco M, Strauss BE, Zatz M (2010) Isolation, characterization, and differentiation potential of canine adipose-derived stem cells. Cell Transplant 19:279
Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7:211
Hui JH, Li L, Teo YH, Ouyang HW, Lee EH (2005) Comparative study of the ability of mesenchymal stem cells derived from bone marrow, periosteum, and adipose tissue in treatment of partial growth arrest in rabbit. Tissue Eng 11:904
Griffin MD, Ritter T, Mahon BP (2010) Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther 21:1641
De Ugarte DA, Morizono K, Elbarbary A, Alfonso Z, Zuk PA, Zhu M, Dragoo JL, Ashjian P, Thomas B, Benhaim P, Chen I, Fraser J, Hedrick MH (2003) Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs 174:101
Ashjian PH, Elbarbary AS, Edmonds B, DeUgarte D, Zhu M, Zuk PA, Lorenz HP, Benhaim P, Hedrick MH (2003) In vitro differentiation of human processed lipoaspirate cells into early neural progenitors. Plast Reconstr Surg 111:1922
Safford KM, Hicok KC, Safford SD, Halvorsen YD, Wilkison WO, Gimble JM, Rice HE (2002) Neurogenic differentiation of murine and human adipose-derived stromal cells. Biochem Biophys Res Commun 294:371
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272:263
Morizono K, De Ugarte DA, Zhu M, Zuk P, Elbarbary A, Ashjian P, Benhaim P, Chen IS, Hedrick MH (2003) Multilineage cells from adipose tissue as gene delivery vehicles. Hum Gene Ther 14:59
Zhang G, Gurtu V, Kain SR (1996) An enhanced green fluorescent protein allows sensitive detection of gene transfer in mammalian cells. Biochem Biophys Res Commun 227:707
Izadpanah R, Kaushal D, Kriedt C, Tsien F, Patel B, Dufour J, Bunnell BA (2008) Long-term in vitro expansion alters the biology of adult mesenchymal stem cells. Cancer Res 68:4229
Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707
Li JY, Christophersen NS, Hall V, Soulet D, Brundin P (2008) Critical issues of clinical human embryonic stem cell therapy for brain repair. Trends Neurosci 31:146
Coyne TM, Marcus AJ, Woodbury D, Black IB (2006) Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia. Stem Cells 24:2483
Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585
Mullen RJ, Buck CR, Smith AM (1992) NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201
Acknowledgments
This work was supported by the National Natural Science Foundation of China (81171089, 30770751, and 81070986), and the Scientific and Technological Projects of Wuhan City of China (2013060602010240).
Conflicts of Interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhang, Y., Liu, N., Tang, Y. et al. Efficient Generation of Neural Stem Cell-Like Cells from Rat Adipose Derived Stem Cells After Lentiviral Transduction with Green Fluorescent Protein. Mol Neurobiol 50, 647–654 (2014). https://doi.org/10.1007/s12035-014-8638-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12035-014-8638-4