Abstract
Previous studies indicate that neural progenitor cells seeded in fibrin can differentiate into the glia cells and neurons. However, whether fibrin gel can induce differentiation of neural progenitor cells of spinal cord into motoneurons remains to be elucidated. In this study, we prepared a fibrin-based hybrid gel incorporated with laminin and fibronectin using rat fresh plasma as a crosslinking agent. The physical properties of this hybrid gel were examined with electron microscope, as well as its degradation and vascularization after subcutaneous transplantation with histological methods. Immunofluorescence stainings were used to study the proliferation and differentiation of the neural progenitor cells seeded in this 3D hybrid gel. The results indicate that such a hybrid gel possesses the unique physical characteristics, and the ability to promote both the proliferation and differentiation of the neural progenitor cells into neuron, including ChAT-positive motoneuron. Thus, it is suggested that this hybrid gel might be suitable for a mimetic tissue transplant for central nerve system injury, such as injured spinal cord repair.
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References
Chai C.; Leong K. W. Biomaterials approach to expand and direct differentiation of stem cells. Mol Ther 15(3): 467–480; 2007.
Cheng H.; Cao Y.; Olson L. Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science 273(5274): 510–513; 1996.
Dikovsky D.; Bianco-Peled H.; Seliktar D. The effect of structural alterations of PEG-fibrinogen hydrogel scaffolds on 3-D cellular morphology and cellular migration. Biomaterials 27(8): 1496–1506; 2006.
Georges P. C.; Miller W. J.; Meaney D. F.; Sawyer E. S.; Janmey P. A. Matrices with compliance comparable to that of brain tissue select neuronal over glial growth in mixed cortical cultures. Biophys J 90(8): 3012–3018; 2006.
Goldman S. Stem and progenitor cell-based therapy of the human central nervous system. Nat biotechnol 23(7): 862–871; 2005.
Ho M.; Yu D.; Davidsion M. C.; Silva G. A. Comparison of standard surface chemistries for culturing mesenchymal stem cells prior to neural differentiation. Biomaterials 27(24): 4333–4339; 2006.
Hokugo A.; Takamoto T.; Tabata Y. Preparation of hybrid scaffold from fibrin and biodegradable polymer fiber. Biomaterials 27(1): 61–67; 2006.
Karimi-Abdolrezaee S.; Eftekharpour E.; Wang J.; Morshead CM.; Fehlings MG. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci 26(13): 3377–3389; 2006.
Ke Y.; Chi L.; Xu R.; Luo C.; Gozal D.; Liu R. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem cells (Dayt. Ohio) 24(4): 1011–1019; 2006.
Kidd K. R.; Williams S. K. Laminin-5-enriched extracellular matrix accelerates angiogenesis and neovascularization in association with ePTFE. J biomed materi res 69(2): 294–304; 2004.
Milner L. D.; Landmesser L. T. Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact. J Neurosci 19(8): 3007–3022; 1999.
Ohori Y.; Yamamoto S.; Nagao M.; Sugimori M.; Yamamoto N.; Nakamura K.; Nakafuku M. Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord. J Neurosci 26(46): 11948–11960; 2006.
Petter-Puchner A. H.; Froetscher W.; Krametter-Froetscher R.; Lorinson D.; Redl H.; van Griensven M. The long-term neurocompatibility of human fibrin sealant and equine collagen as biomatrices in experimental spinal cord injury. Exp Toxicol Pathol 58(4): 237–245; 2007.
Pittier R.; Sauthier F.; Hubbell J. A.; Hall H. Neurite extension and in vitro myelination within three-dimensional modified fibrin matrices. J neurobiol 63(1): 1–14; 2005.
Pollard S. M.; Parsons M. J.; Kamei M.; Kettleborough R. N.; Thomas K. A.; Pham V. N.; Bae M. K.; Scott A.; Weinstein B. M.; Stemple D. L. Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation. Dev biol 289(1): 64–76; 2006.
Schense J. C.; Bloch J.; Aebischer P.; Hubbell J. A. Enzymatic incorporation of bioactive peptides into fibrin matrices enhances neurite extension. Nat biotechnol 18(4): 415–419; 2000.
Schmal H.; Mehlhorn A. T.; Fehrenbach M.; Muller C. A.; Finkenzeller G.; Sudkamp N. P. Regulative mechanisms of chondrocyte adhesion. Tissue eng 12(4): 741–750; 2006.
Sreerekha P. R.; Divya P.; Krishnan L. K. Adult stem cell homing and differentiation in vitro on composite fibrin matrix. Cell prolif 39(4): 301–312; 2006.
Taylor S. J.; Rosenzweig E. S.; McDonald 3rd J. W.; Sakiyama-Elbert S. E. Delivery of neurotrophin-3 from fibrin enhances neuronal fiber sprouting after spinal cord injury. J Control Release 113(3): 226–235; 2006.
Ziv Y.; Avidan H.; Pluchino S.; Martino G.; Schwartz M. Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury. Proc Natl Acad Sci USA 103(35): 13174–13179; 2006.
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This study was supported by two grants from National Natural Science Foundation of China (NSCF) (Project 30570981 and 30571878).
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Editor: J. Denry Sato
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Liu, J., Zhang, Z., Gong, A. et al. Neuronal progenitor cells seeded in fibrin gel differentiate into ChAT-positive neuron. In Vitro Cell.Dev.Biol.-Animal 46, 738–745 (2010). https://doi.org/10.1007/s11626-010-9331-1
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DOI: https://doi.org/10.1007/s11626-010-9331-1