3. Bossolasco P, Cova L, Calzarossa C, Rimoldi SG, Borsotti C, et al. (2005) Neuro-glial differentiation of human bone marrow stem cells in vitro. Exp Neurol 193: 312–325. 4. Hermann A, Gastl R, Liebau S, Popa MO, Fiedler J, et al. (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117: 4411–4422. 5. Lei Z, Yongda L, Jun M, Yingyu S, Shaoju Z, et al. (2007) Culture and neural differentiation of rat bone marrow mesenchymal stem cells in vitro. Cell Biol Int 31: 916–923. 6. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, et al. (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164: 247–256. 7. Scintu F, Reali C, Pillai R, Badiali M, Sanna MA, et al. (2006) Differentiation of human bone marrow stem cells into cells with a neural phenotype: diverse effects of two specific treatments. BMC Neurosci 7: 14. 8. Suzuki H, Taguchi T, Tanaka H, Kataoka H, Li Z, et al. (2004) Neurospheres induced from bone marrow stromal cells are multipotent for differentiation into neuron, astrocyte, and oligodendrocyte phenotypes. Biochem Biophys Res Commun 322: 918–922. 9. Woodbury D, Schwarz EJ, Prockop DJ, Black IB (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res 61: 364–370. 10. Deng W, Obrocka M, Fischer I, Prockop DJ (2001) In vitro differentiation of human marrow stromal cells into early progenitors of neural cells by conditions that increase intracellular cyclic AMP. Biochem Biophys Res Commun 282: 148–152. 11. Jin K, Mao XO, Batteur S, Sun Y, Greenberg DA (2003) Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression. Exp Neurol 184: 78–89. 12. Kabos P, Ehtesham M, Kabosova A, Black KL, Yu JS (2002) Generation of neural progenitor cells from whole adult bone marrow. Exp Neurol 178: 288–293. 13. Kohyama J, Abe H, Shimazaki T, Koizumi A, Nakashima K, et al. (2001) Brain from bone: efficient ‘‘meta-differentiation’’ of marrow stroma-derived mature osteoblasts to neurons with Noggin or a demethylating agent. Differentiation 68: 235–244. 14. Alexanian AR, Maiman DJ, Kurpad SN, Gennarelli TA (2008) In vitro and in vivo Characterization of Neurally Modified Mesenchymal Stem Cells Induced by Epigenetic Modifiers and Neural Stem Cell Environment. Stem Cells Dev. 15. Corti S, Locatelli F, Strazzer S, Salani S, Del Bo R, et al. (2002) Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment. Exp Neurol 177: 443–452. 16. Munoz-Elias G, Marcus AJ, Coyne TM, Woodbury D, Black IB (2004) Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival. J Neurosci 24: 4585–4595. 17. Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ (1998) Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats–similarities to astrocyte grafts. Proc Natl Acad Sci U S A 95: 3908–3913. 18. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290: 1775–1779. 19. Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci U S A 96: 10711–10716. 20. Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, et al. (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci U S A 100: 1364–1369. 21. Svendsen CN, Caldwell MA, Ostenfeld T (1999) Human neural stem cells: isolation, expansion and transplantation. Brain Pathol 9: 499–513. 22. Munoz-Elias G, Woodbury D, Black IB (2003) Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions. Stem Cells 21: 437–448. 23. Gurok U, Steinhoff C, Lipkowitz B, Ropers HH, Scharff C, et al. (2004) Gene expression changes in the course of neural progenitor cell differentiation. J Neurosci 24: 5982–6002. 24. Hsieh J, Gage FH (2004) Epigenetic control of neural stem cell fate. Curr Opin Genet Dev 14: 461–469. 25. Taschenberger H, Scheuss V, Neher E (2005) Release kinetics, quantal parameters and their modulation during short-term depression at a developing synapse in the rat CNS. J Physiol 568: 513–537. 26. Lu P, Blesch A, Tuszynski MH (2004) Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 77: 174–191. 27. Neuhuber B, Gallo G, Howard L, Kostura L, Mackay A, et al. (2004) Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype. J Neurosci Res 77: 192–204. 28. Krampera M, Marconi S, Pasini A, Galie M, Rigotti G, et al. (2007) Induction of neural-like differentiation in human mesenchymal stem cells derived from bone marrow, fat, spleen and thymus. Bone 40: 382–390. Induced MSC Are Not Neurons 29. Rismanchi N, Floyd CL, Berman RF, Lyeth BG (2003) Cell death and long-term maintenance of neuron-like state after differentiation of rat bone marrow stromal cells: a comparison of protocols. Brain Res 991: 46–55. 30. Wenisch S, Trinkaus K, Hild A, Hose D, Heiss C, et al. (2006) Immunochemical, ultrastructural and electrophysiological investigations of bone-derived stem cells in the course of neuronal differentiation. Bone 38: 911–921. 31. Kelly CM, Tyers P, Borg MT, Svendsen CN, Dunnett SB, et al. (2005) EGF and FGF-2 responsiveness of rat and mouse neural precursors derived from the embryonic CNS. Brain Res Bull 68: 83–94. 32. Brewer GJ (1995) Serum-free B27/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus. J Neurosci Res 42: 674–683. 33. Pfeiffer CM, Huff DL, Gunter EW (1999) Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin Chem 45: 290–292. 34. Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19: 180–192. 35. Croft AP, Przyborski SA (2006) Formation of neurons by non-neural adult stem cells: potential mechanism implicates an artifact of growth in culture. Stem Cells 24: 1841–1851. 36. Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, et al. (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomy- ocytes and hepatocytes. Nature 425: 968–973. 37. Bae JS, Han HS, Youn DH, Carter JE, Modo M, et al. (2007) Bone marrow- derived mesenchymal stem cells promote neuronal networks with functional synaptic transmission after transplantation into mice with neurodegeneration. Stem Cells 25: 1307–1316. 38. Goolsby J, Marty MC, Heletz D, Chiappelli J, Tashko G, et al. (2003) Hematopoietic progenitors express neural genes. Proc Natl Acad Sci U S A 100: 14926–14931. 39. Lu P, Tuszynski MH (2005) Can bone marrow-derived stem cells differentiate into functional neurons? Exp Neurol 193: 273–278. 40. Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, et al. (2004) Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells ‘hide out’ in the bone marrow. Leukemia 18: 29–40. 41. Tondreau T, Lagneaux L, Dejeneffe M, Massy M, Mortier C, et al. (2004) Bone marrow-derived mesenchymal stem cells already express specific neural proteins before any differentiation. Differentiation 72: 319–326. 42. Woodbury D, Reynolds K, Black IB (2002) Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 69: 908–917. 43. Schoenherr CJ, Anderson DJ (1995) The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-specific genes. Science 267: 1360–1363. 44. Kuwabara T, Hsieh J, Nakashima K, Taira K, Gage FH (2004) A small modulatory dsRNA specifies the fate of adult neural stem cells. Cell 116: 779–793. 45. Martin D, Tawadros T, Meylan L, Abderrahmani A, Condorelli DF, et al. (2003) Critical role of the transcriptional repressor neuron-restrictive silencer factor in the specific control of connexin36 in insulin-producing cell lines. J Biol Chem 278: 53082–53089. 46. Beyer Nardi N, da Silva Meirelles L (2006) Mesenchymal stem cells: isolation, in vitro expansion and characterization. Handb Exp Pharmacol. pp 249–282. 47. Laterza OF, Modur VR, Crimmins DL, Olander JV, Landt Y, et al. (2006) Identification of novel brain biomarkers. Clin Chem 52: 1713–1721. 48. Jones DP, Go YM, Anderson CL, Ziegler TR, Kinkade JM Jr., et al. (2004) Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control. Faseb J 18: 1246–1248. 49. Liu Y, Gutterman DD (2002) Oxidative stress and potassium channel function. Clin Exp Pharmacol Physiol 29: 305–311. 50. Miller BA (2006) The role of TRP channels in oxidative stress-induced cell death. J Membr Biol 209: 31–41. 51. Hool LC, Corry B (2007) Redox control of calcium channels: from mechanisms to therapeutic opportunities. Antioxid Redox Signal 9: 409–435. 52. Sagara JI, Makino N (2007) Glutathione Induces Neuronal Differentiation in Rat Bone Marrow Stromal Cells. Neurochem Res. 53. Hille B (2001) Ion Channels of Excitable Membranes. Sunderland, MA: Sinauer Associates. 814 p. 54. Goodwin PA, Campbell KE, Evans BA, Wann KT (1998) In vitro patch-clamp studies in skin fibroblasts. J Pharmacol Toxicol Methods 39: 229–233. 55. Li GR, Deng XL, Sun H, Chung SS, Tse HF, et al. (2006) Ion channels in mesenchymal stem cells from rat bone marrow. Stem Cells 24: 1519–1528. 56. Lang F, Huber SM, Szabo I, Gulbins E (2007) Plasma membrane ion channels in suicidal cell death. Arch Biochem Biophys 462: 189–194. 57. Bortner CD, Cidlowski JA (2007) Cell shrinkage and monovalent cation fluxes: role in apoptosis. Arch Biochem Biophys 462: 176–188. 58. Watanabe M, Sakimura K, Takahashi Y, Kondo H (1990) Ontogenic changes in expression of neuron-specific enolase (NSE) and its mRNA in the Purkinje cells of the rat cerebellum: immunohistochemical and in situ hybridization study. Brain Res Dev Brain Res 53: 89–96. PLoS ONE | www.plosone.org 11 April 2009 | Volume 4 | Issue 4 | e5222