Control of in vitro neural differentiation of mesenchymal stem cells in 3D macroporous, cellulosic hydrogels.

BACKGROUND Mesenchymal stem cells (MSCs) are multipotent cells that can be induced to differentiate into multiple cell lineages, including neural cells. They are a good cell source for neural tissue-engineering applications. Cultivation of human (h)MSCs in 3D scaffolds is an effective means for the development of novel neural tissue-engineered constructs, and may serve as a promising strategy in the treatment of nerve injury. AIM This study presents the in vitro growth and neural differentiation of hMSCs in 3D macroporous, cellulosic hydrogels. RESULTS The number of hMSCs cultivated in the 3D scaffolds increased by more than 14-fold after 7 days. After 2 days induction, most of the hMSCs in the 3D scaffolds were positive for nestin, a marker of neural stem cells. After 7 days induction, most of the hMSCs in the 3D scaffolds showed glial fibrillary acidic protein, tubulin or neurofilament M-positive reaction and a few hMSCs were positive for nestin. After 14 days induction, hMSCs in the 3D scaffolds could completely differentiate into neurons and glial cells. The neural differentiation of hMSCs in the 3D scaffolds was further demonstrated by real-time PCR. CONCLUSION These results show that the 3D macroporous cellulosic hydrogel could be an appropriate substrate for neural differentiation of hMSCs and its possible applications in neural tissue engineering are discussed.

[1]  L. Yajun,et al.  Effects of Notch-1 signalling pathway on differentiation of marrow mesenchymal stem cells into neurons in vitro , 2007, Neuroreport.

[2]  T. Scheper,et al.  Fast and efficient screening system for new biomaterials in tissue engineering: a model for peripheral nerve regeneration. , 2007, Journal of biomedical materials research. Part A.

[3]  Mara Riminucci,et al.  Bone Marrow Stromal Stem Cells: Nature, Biology, and Potential Applications , 2001, Stem cells.

[4]  Irving L. Weissman,et al.  Stem cells [14] , 1991 .

[5]  Ingo Heschel,et al.  In vitro cell alignment obtained with a Schwann cell enriched microstructured nerve guide with longitudinal guidance channels. , 2009, Biomaterials.

[6]  F. Gage,et al.  Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons , 2002, Nature Neuroscience.

[7]  M. Richards,et al.  History and perspective of stem cell research. , 2004, Best practice & research. Clinical obstetrics & gynaecology.

[8]  Robert H Miller.  The promise of stem cells for neural repair , 2006, Brain Research.

[9]  T. Nandedkar,et al.  Stem cell research: its relevance to reproductive biology. , 2003, Indian journal of experimental biology.

[10]  Steven J. Greco,et al.  Neurons Derived From Human Mesenchymal Stem Cells Show Synaptic Transmission and Can Be Induced to Produce the Neurotransmitter Substance P by Interleukin‐1α , 2005, Stem cells.

[11]  M. Horne,et al.  Enhancing neurite outgrowth from primary neurones and neural stem cells using thermoresponsive hydrogel scaffolds for the repair of spinal cord injury. , 2009, Journal of biomedical materials research. Part A.

[12]  S. Endo,et al.  Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice. , 2005, Human gene therapy.

[13]  H. Müller,et al.  Experimental strategies to promote axonal regeneration after traumatic central nervous system injury , 1998, Progress in Neurobiology.

[14]  T. Dóczi,et al.  Traumatic axonal injury in the spinal cord evoked by traumatic brain injury. , 2008, Journal of neurotrauma.

[15]  F. Gage,et al.  Mammalian neural stem cells. , 2000, Science.

[16]  Young-tae Kim,et al.  In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. , 2006, Biomaterials.

[17]  Mark Moller.  Human embryonic stem cell research, justice, and the problem of unequal biological access , 2008, Philosophy, ethics, and humanities in medicine : PEHM.

[18]  Christine E Schmidt,et al.  Nanostructured scaffolds for neural applications. , 2008, Nanomedicine.

[19]  Ren-zheng Huang,et al.  Dorsal root ganglion neurons induce transdifferentiation of mesenchymal stem cells along a Schwann cell lineage , 2008, Neuroscience Letters.

[20]  Christine E Schmidt,et al.  Neural tissue engineering: strategies for repair and regeneration. , 2003, Annual review of biomedical engineering.

[21]  J. Sipe,et al.  Tissue Engineering and Reparative Medicine , 2002, Annals of the New York Academy of Sciences.

[22]  N. Scolding,et al.  Protecting axons in multiple sclerosis , 2008, Multiple sclerosis.

[23]  S. Hollister,et al.  Brain cortex regeneration affected by scaffold architectures. , 2008, Journal of neurosurgery.

[24]  M. Shoichet,et al.  Characterization of neural stem cells on electrospun poly(ε-caprolactone) submicron scaffolds: evaluating their potential in neural tissue engineering , 2008, Journal of biomaterials science. Polymer edition.

[25]  G. Raisman.  Repair of spinal cord injury: ripples of an incoming tide, or how I spent my first 40 years in research , 2006, Spinal Cord.

[26]  M. Ko,et al.  Conversion of Human Umbilical Cord Mesenchymal Stem Cells in Wharton's Jelly to Dopaminergic Neurons In Vitro: Potential Therapeutic Application for Parkinsonism , 2006, Stem cells.