Treating spinal cord injury in rats with a combination of human fetal neural stem cells and hydrogels modified with serotonin

• Autorzy: Ruzicka J. , Romanyuk N. , Hejcl A. , Vetrik M. , Hruby M. , Cocks G. , Cihlar J. , Pradny M. , Price J. , Sykova E. , Jendelova P.
• Języki publikacji: EN

Abstrakty

EN

Currently, there is no effective strategy for the treatment of spinal cord injury (SCI). A combination of biomaterials and stem cell therapy seems to be a promising approach to increase regenerative potential after SCI. We evaluated the use of a cell-polymer construct based on a combination of the conditionally immortalized spinal progenitor cell line SPC-01_GFP3, derived from human fetal spinal cord tissue, with a serotonin-modified poly(2-hydroxyethyl methacrylate) hydrogel (pHEMA-5HT). We compared the effect of treatment with a pHEMA-5HT hydrogel seeded with SPC-01_GFP3 cells, treatment with a pHEMA-5HT only and no treatment on functional outcome and tissue reconstruction in hemisected rats. Prior to transplantation the cell-polymer construct displayed a high potential to support the growth, proliferation and differentiation of SPC-01 cells in vitro. One month after surgery, combined hydrogel-cell treatment reduced astrogliosis and tissue atrophy and increased axonal and blood vessel ingrowth into the implant; however, two months later only the ingrowth of blood vessels remained increased. SPC-01_GFP3 cells survived well in vivo and expressed advanced markers of neuronal differentiation. However, a majority of the transplanted cells migrated out of the lesion and only rarely remained in the hydrogel. No differences among the groups in motor or sensory recovery were observed. Despite the support of the hydrogel as a cell carrier in vitro, and good results in vivo one month postsurgery, there was only a small effect on long term recovery, mainly due to the limited ability of the hydrogels to support the in vivo growth and differentiation of cells within the implant. Further modifications will be necessary to achieve stable long term improvement in functional outcome.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.102-115,fig.,ref.

Twórcy

autor

Ruzicka J.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic
• Department of Neuroscience, 2 nd Faculty of Medicine, Charles University, Prague, Czech Republic

autor

Romanyuk N.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic

autor

Hejcl A.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic
• Department of Neurosurgery, Masaryk Hospital, Usti nad Labem, Czech Republic

autor

Vetrik M.

• Institute of Macromolecular Chemistry ASCR, Prague, Czech Republic
• Faculty of Scence, Charles University, Prague, Czech Republic

autor

Hruby M.

• Institute of Macromolecular Chemistry ASCR, Prague, Czech Republic

autor

Cocks G.

• Institute of Psychiatry, Kings College London, London, United Kingdom

autor

Cihlar J.

• Department of Mathematics, Faculty of Science, J.E. Purkynje University, Usti nad Labem, Czech Republic

autor

Pradny M.

• Institute of Macromolecular Chemistry ASCR, Prague, Czech Republic

autor

Price J.

• Institute of Psychiatry, Kings College London, London, United Kingdom

autor

Sykova E.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic
• Department of Neuroscience, 2 nd Faculty of Medicine, Charles University, Prague, Czech Republic

autor

Jendelova P.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic
• Department of Neuroscience, 2 nd Faculty of Medicine, Charles University, Prague, Czech Republic

Bibliografia

• Aizawa Y, Leipzig N, Zahir T, Shoichet M (2008) The effect of immobilized platelet derived growth factor AA on neu¬ral stem/progenitor cell differentiation on cell-adhesive hydrogels. Biomaterials 29: 4676-4683.
• Amemori T, Romanyuk N, Jendelova P, Herynek V, Turnovcova K, Marekova D, Kapcalova M, Price J, Sykova E (2011) Human fetal spinal stem cells improve locomotor function after spinal cord injury in the rat. Glia 59 (S1): S84-S85.
• Austin JW, Kang CE, Baumann MD, DiDiodato L, Satkunendrarajah K, Wilson JR, Stanisz GJ, Shoichet MS, Fehlings MG (2012) The effects of intrathecal injec¬tion of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis. Biomaterials 33: 4555-4564.
• Bakshi A, Fisher O, Dagci T, Himes BT, Fischer I, Lowman A (2004) Mechanically engineered hydrogel scaffolds for axonal growth and angiogenesis after transplantation in spinal cord injury. J Neurosurg Spine 1: 322-329.
• Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12: 1-21.
• Blesch A, Lu P, Tuszynski MH (2002) Neurotrophic factors, gene therapy, and neural stem cells for spinal cord repair. Brain Res Bull 57: 833-838.
• Buzanska L, Ruiz A, Zychowicz M, Rauscher H, Ceriotti L, Rossi F, Colpo P, Domanska-Janik K, Coecke S (2009) Patterned growth and differentiation of human cord blood-derived neural stem cells on bio-functionalized surfaces. Acta Neurobiol Exp (Wars) 69: 24-36.
• Cummings BJ, Uchida N, Tamaki SJ, Salazar DL, Hooshmand M, Summers R, Gage FH, Anderson AJ (2005) Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci U S A 102: 14069-14074.
• Fehlings MG, Rabin D, Sears W, Cadotte DW, Aarabi B (2010) Current practice in the timing of surgical intervention in spinal cord injury. Spine (Phila Pa 1976) 35: S166-173.
• Fitch MT, Silver J (2008) CNS injury, glial scars, and inflammation: Inhibitory extracellular matrices and regen¬eration failure. Exp Neurol 209: 294-301.
• Fouad K, Schnell L, Bunge MB, Schwab ME, Liebscher T, Pearse DD (2005) Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase pro¬motes locomotor recovery after complete transection of the spinal cord. J Neurosci 25: 1169-1178.
• Hejcl A, Lesny P, Pradny M, Sedy J, Zamecnik J, Jendelova P, Michalek J, Sykova E (2009) Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydro¬gels with positive and negative surface charges and poly- electrolyte complexes in spinal cord injury repair. J Mater Sci Mater Med 20: 1571-1577.
• Hooshmand MJ, Sontag CJ, Uchida N, Tamaki S, Anderson AJ, Cummings BJ (2009) Analysis of host-mediated repair mechanisms after human CNS-stem cell transplan¬tation for spinal cord injury: correlation of engraftment with recovery. PLoS One 4: e5871.
• Jakeman LB, Wei P, Guan Z, Stokes BT (1998) Brain- derived neurotrophic factor stimulates hindlimb stepping and sprouting of cholinergic fibers after spinal cord inju¬ry. Exp Neurol 154: 170-184.
• Jones LL, Oudega M, Bunge MB, Tuszynski MH (2001) Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury. J Physiol 533: 83-89.
• Jung H, Lacombe J, Mazzoni EO, Liem KF, Jr., Grinstein J, Mahony S, Mukhopadhyay D, Gifford DK, Young RA, Anderson KV, Wichterle H, Dasen JS (2010) Global con¬trol of motor neuron topography mediated by the repres¬sive actions of a single hox gene. Neuron 67: 781-796.
• Karimi-Abdolrezaee S, Eftekharpour E, Wang J, Morshead CM, Fehlings MG (2006) Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci 26: 3377-3389.
• Khurshid SS, Schmidt CE, Peppas NA (2010) optimization of molecularly imprinted polymers of serotonin for bio¬material applications. J Biomater Sci Polym Ed [Epub ahead of print]
• Kubinova S, Horak D, Sykova E (2009) Cholesterol-modified superporous poly(2-hydroxyethyl methacrylate) scaffolds for tissue engineering. Biomaterials 30: 4601-4609.
• Kubinova S, Horak D, Kozubenko N, Vanecek V, Proks V, Price J, Cocks G, Sykova E (2010) The use of superporous Ac-CGGASIKVAVS-OH-modified PHEMA scaffolds to promote cell adhesion and the differentiation of human fetal neural precursors. Biomaterials 31: 5966-5975.
• Kwon BK, Tetzlaff W, Grauer JN, Beiner J, Vaccaro AR (2004) Pathophysiology and pharmacologic treatment of acute spinal cord injury. Spine J 4: 451-464.
• Lieb E, Hacker M, Tessmar J, Kunz-Schughart LA, Fiedler J, Dahmen C, Hersel U, Kessler H, Schulz MB, Gopferich A (2005) Mediating specific cell adhesion to low-adhe¬sive diblock copolymers by instant modification with cyclic RGD peptides. Biomaterials 26: 2333-2341.
• Moradi F, Bahktiari M, Joghataei MT, Nobakht M, Soleimani M, Hasanzadeh G, Fallah A, Zarbakhsh S, Hejazian LB, Shirmohammadi M, Maleki F BD (2012) PuraMatrix peptide hydrogel as a culture system for human fetal Schwann cells in spinal cord regeneration. J Neurosci Res 90: 2335-2348.
• Nandoe Tewarie RS, Hurtado A, Bartels RH, Grotenhuis A, Oudega M (2009) Stem cell-based therapies for spinal cord injury. J Spinal Cord Med 32: 105-114.
• Niapour A, Karamali F, Nemati S, Taghipour Z, Mardani M, Nasr-Esfahani MH, Baharvand H (2012) Cotransplantation of human embryonic stem cell-derived neural progenitors and schwann cells in a rat spinal cord contusion injury model elicits a distinct neurogenesis and functional recovery. Cell Transplant 21: 827-843.
• Oyinbo CA (2011) Secondary injury mechanisms in trau¬matic spinal cord injury: A nugget of this multiply cas¬cade. Acta Neurobiol Exp (Wars) 71: 281-299.
• Peng ZW, Xue YY, Wang HN, Wang HH, Xue F, Kuang F, Wang BR, Chen YC, Zhang LY, Tan QR (2012) Sertraline promotes hippocampus-derived neural stem cells differ¬entiating into neurons but not glia and attenuates LPS- induced cellular damage. Prog Neuropsychopharmacol Biol Psychiatry 36: 183-188.
• Piantino J, Burdick JA, Goldberg D, Langer R, Benowitz LI (2006) An injectable, biodegradable hydrogel for trophic fac¬tor delivery enhances axonal rewiring and improves perfor¬mance after spinal cord injury. Exp Neurol 201: 359-367.
• Platel JC, Stamboulian S, Nguyen I, Bordey A (2010) Neurotransmitter signaling in postnatal neurogenesis: The first leg. Brain Res Rev 63: 60-71.
• Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassie P, Thicoipe M, Dabadie P (2000) Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38: 71-76.
• Pollock K, Stroemer P, Patel S, Stevanato L, Hope A, Miljan E, Dong Z, Hodges H, Price J, Sinden JD (2006) A con¬ditionally immortal clonal stem cell line from human cortical neuroepithelium for the treatment of ischemic stroke. Exp Neurol 199:143-155.
• Price J, Cocks G (2011) Neural stem cells from human spi¬nal cord as potential therapies and as models of disease. Glia 59: S14-S15.
• Ruff CA, Wilcox JT, Fehlings MG (2012) Cell-based trans¬plantation strategies to promote plasticity following spi¬nal cord injury. Exp Neurol 235: 78-90.
• Sykova E, Jendelova P, Urdzikova L, Lesny P, Hejcl A (2006) Bone marrow stem cells and polymer hydrogels-- two strategies for spinal cord injury repair. Cell Mol Neurobiol 26: 1113-1129.
• Urdzikova L, Jendelova P, Glogarova K, Burian M, Hajek M, Sykova E (2006) Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma 23: 1379-1391.
• Woerly S, Doan VD, Sosa N, de Vellis J, Espinosa-Jeffrey A (2004) Prevention of gliotic scar formation by NeuroGel allows partial endogenous repair of transected cat spinal cord. J Neurosci Res 75: 262-272.
• Zychowicz M, Mehn D, Ruiz A, Colpo P, Rossi F, Frontczak- Baniewicz M, Domanska-Janik K, Buzanska L (2011) Proliferation capacity of cord blood derived neural stem cell line on different micro-scale biofunctional domains. Acta Neurobiol Exp (Wars) 71: 12-23.

Uwagi

Rekord w opracowaniu