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Differentiation Potential of Human Bone Marrow Mesenchymal Stem Cells into Motorneuron-like Cells on Electrospun Gelatin Membrane

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Abstract

Human bone marrow-derived mesenchymal stem cells are potent types of cells with self renewal ability and immunomodulatory properties. They not only have the capacity to differentiate into mesodermal lineages, but they are also capable to transdifferentiate into neural cells in vitro and in vivo. From a biological point of view, the specification of cell fate in the central nervous system is largely dictated by retinoic acid and sonic hedgehog. In addition with inductive molecules, electrospun three dimensional (3D) scaffolds with similar properties to natural extracellular matrix represent a physiological environment that could better resemble the in vivo microenvironment in comparison with two dimensional culture systems. In this regard, the aim of this study was to examine whether induction of human BM-MSCs with retinoic acid (RA) and sonic hedgehog (Shh) in combination with electrospun gelatin scaffold could lead to better differentiation of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) into motorneuron-like cells in vitro.

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References

  • Abbott A (2003) Cell culture: biology’s new dimension. Nature 424:870–872

    Article  CAS  PubMed  Google Scholar 

  • Baiguera S, Del Guadio C, Lucatelli E, Kuevda E, Boieri M, Mazzanti B, Bianco A, Macchiarini P (2014) Electrospun gelatin scaffolds incorporating rat decellularized brain extracellular matrix for neural tissue engineering. Biomaterials 35(4):1205–1214

    Article  CAS  PubMed  Google Scholar 

  • Bassi EJ, Aita CAM, Câmara NOS (2011) Immune regulatory properties of multipotent mesenchymal stromal cells: where do we stand? World J Stem Cells 3:1–8

    Article  PubMed Central  PubMed  Google Scholar 

  • Brejot T, Blanchard S, Hocquemiller M, Haase G (2006) Forced expression of the motor neuron determinant HB9 in neural stem cells affects neurogenesis. Exp Neurol 198:167–182

    Article  CAS  PubMed  Google Scholar 

  • Briscoe J, Chen Y, Jessell TM, Struhl G (2001) A hedgehog-insensitive form of patched provides evidence for direct long-range morphogen activity of sonic hedgehog in the neural tube. Mol Cell 7:1279–1291

    Article  CAS  PubMed  Google Scholar 

  • Diez del Corral R, Olivera-Martinez I, Goriely A, Gale E, Maden M (2003) Opposing FGF and retinoid pathways control ventral neural pattern, neuronal differentiation, and segmentation during body axis extension. Neuron 40:65–79

    Article  CAS  PubMed  Google Scholar 

  • Ericson J, Rashbass P, Schedl A, Brenner-Morton S, Kawakami A (1997) Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. Cell 90:169–180

    Article  CAS  PubMed  Google Scholar 

  • Faghihi F, Baghaban Eslaminejad M, Nekookar A, Najar M, Salekdeh GH (2013) The effect of purmorphamine and sirolimus on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells. Biomed Pharmacother 67:31–38

    Article  CAS  PubMed  Google Scholar 

  • Friedenstein AJ, Piatetzky-Shapiro II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390

    CAS  PubMed  Google Scholar 

  • Ghasemi-obarakeh L, Prabhakaran MP, Morshed M, Nasr-esfahani MH, Ramakrishnan S (2008) Electrospun poly(epsilon-caprolactone)/gelatin nanofibrous scaffolds for nerve tissue engineering. Biomaterials 29(34):4532–4539

    Article  Google Scholar 

  • Griffith LG, Swartz MA (2006) Capturing complex 3D tissue physiology in vitro. Nat Rev Mol Cell Biol 7(3):211–24

    Article  CAS  PubMed  Google Scholar 

  • Hajiali H, Shahgasempour S, Naimi-Jamal MR, Peirovi H (2011) Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering. Int J Nanomedicine 6:2133–2141

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hermann A, Gastl R, Liebau S, Oana Popa M, Fiedler J, Boehm BO, Maisel M, Lerche H, Schwarz J, Brenner R, Storch A (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117:4411–4422

    Article  CAS  PubMed  Google Scholar 

  • Jaiswal RK, Jaiswal N, Bruder SP, Mbalaviele G, Marshak DR, Pittenger MF (2000) Adult human mesenchymal stem cell differentiation to the osteogenic or adipogenic lineage is regulated by mitogen-activated protein kinase. J Biol Chem 275:9645–52

    Article  CAS  PubMed  Google Scholar 

  • Jessell TM (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat Rev Genet 1:20–29

    Article  CAS  PubMed  Google Scholar 

  • Karumbayaram S, Novitch BG, Patterson M, Umbach JA, Richter L, Lindgren A (2009) Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells 27:806–811

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lee SK, Paff SL (2003) Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors. Neuron 38:731–745

    Article  CAS  PubMed  Google Scholar 

  • Liou HM, Rau LR, Huang CC, Lu (2013) Electrospun Hyaluronan- gelatin nanofibrous matrix for nerve tissue engineering. J Nanomaters, 613–628

  • Liqing Y, Jia G, Jiqing C, Ran G, Fei C, Jie K, Yanyun W, Cheng Z (2011) Directed differentiation of motor neuron cell-like cells from human adipose-derived stem cells in vitro. NeuroReport 22:370–373

    Article  PubMed  Google Scholar 

  • Maden M (2002) Retinoid signalling in the development of the central nervous system. Nat Rev Neurosci 3:843–853

    Article  CAS  PubMed  Google Scholar 

  • Martín-López E, Nieto-Díaz M, Nieto-Sampedro M (2012) Differential adhesiveness and neurite-promoting activity for neural cells of chitosan, gelatin, and poly-L-lysine films. J Biomater Appl 26(7):791–809

    Article  PubMed  Google Scholar 

  • Mota A, Sahebghadam Lotfi A, Barzin J, Hatam M, Adibi M, Khalaj Z, Massumi M (2014) Human bone marrow mesenchymal stem cell behaviors on PCL/gelatin nanofibrous scaffolds modified with a collagen IV- derived RGD- containing peptide. Cell J 16(1):1–10

    PubMed Central  CAS  PubMed  Google Scholar 

  • Novitch B, Wichterle H, Jessell T, Sockanathan S (2003) A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification. Neuron 40:81–95

    Article  CAS  PubMed  Google Scholar 

  • Ozeki M, Tabata Y (2005) In vivo degradability of hydrogels prepared from different gelatins by various crosslinking method. J Biomater Sci Polym Ed 16(5):549–561

    Article  CAS  PubMed  Google Scholar 

  • Park HW, Cho JS, Park CK, Jung SJ, Park CH (2012) Directed induction of functional motor neuron-like cells from genetically engineered human mesenchymal stem cells. PLoS ONE 7(4):e35244

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas JD (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  CAS  PubMed  Google Scholar 

  • Ratanavaraporn J, Damrongsakkul S, Sanchavanakit N, Banaprasert T, Kanokpanont S (2006) Comparison of gelatin and collagen scaffolds for fibroblast cell culture. J Metals Mater Miner 16:31–36

    CAS  Google Scholar 

  • Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256

    Article  CAS  PubMed  Google Scholar 

  • Schacter DL, Gilbert DT, Wegner DM (2011) Psychology, 2nd ed., New York

  • Schwartz PH (2006) The potential of Stm cell therapies for neurological diseases. Expert Rev Neurother 6(2):153–161

    Article  CAS  PubMed  Google Scholar 

  • Shahbazi E, Kiani S, Gourabi H, Baharvand H (2011) Electrospun nanofibrillar surfaces promote neuronal differentiation and function from human embryonic stem cells. Tissue Eng A 17(23–24):3021–3031

    Article  CAS  Google Scholar 

  • Sisson K, Zhang C, Farach-Carson MC, Chase B, Rabolt JF (2009) Evaluation of cross-linking methods for electrospun gelatin on cell growth and viability. Biomacromolecules 10(7):1675–1680

    Article  CAS  PubMed  Google Scholar 

  • Skotak M, Noriega S, Larsen G, Subramanian A (2010) Electrospun cross-linked gelatin fibers with controlled diameter: the effect of matrix stiffness on proliferative and biosynthetic activity of chondrocytes cultured in vitro. J Biomed Mater Res A 95a(3):828–836

    Article  CAS  Google Scholar 

  • Sockanathan S, Jessell TM (1998) Motor neuron-derived retinoid signaling specifies the subtype identity of spinal motor neurons. Cell 94:503–514

    Article  CAS  PubMed  Google Scholar 

  • Solchaga LA, Penick KJ, Welter JF (2011) Chondrogenic differentiation of bone marrow-derived mesenchymal stem cells: tips and tricks. Methods Mol Biol 698:253–78

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Thaler JP, Koo SJ, Kania A, Lettieri K, Andrews S (2004) A postmitotic role for Isl-class LIM homeodomain proteins in the assignment of visceral spinal motor neuron identity. Neuron 41:337–350

    Article  CAS  PubMed  Google Scholar 

  • Wichterle H, Lieberam I, Porter JA, Jessell TM (2002) Directed differentiation of embryonic stem cells into motor neurons. Cell 110:385–397

    Article  CAS  PubMed  Google Scholar 

  • Woodbury D, Reynolds K, Black B (2002) Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. J Neurosci Res 69(6):908–917

    Article  CAS  PubMed  Google Scholar 

  • Zhang YZ, Venugopal J, Huang ZM, Lim CT, Ramakrishna S (2006) Crosslinking of the electrospun gelatin nanofibers. Polymer 47:2911–2917

    Article  CAS  Google Scholar 

  • Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC (2002) Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 174:11–20

    Article  PubMed  Google Scholar 

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Acknowledgments

This study was financially supported by Iran National Science Foundation (INSF).

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The authors declare that they have no conflicts of interest.

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Correspondence to Mohammad Taghi Joghataei.

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Faghihi, F., Mirzaei, E., Sarveazad, A. et al. Differentiation Potential of Human Bone Marrow Mesenchymal Stem Cells into Motorneuron-like Cells on Electrospun Gelatin Membrane. J Mol Neurosci 55, 845–853 (2015). https://doi.org/10.1007/s12031-014-0437-x

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  • DOI: https://doi.org/10.1007/s12031-014-0437-x

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