Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord
Patist, Carla M; Borgerhoff Mulder, Masha; Gautier, Sandrineet al.
[en] The effects of poly(D,L-lactic acid) macroporous guidance scaffolds (foams) with or without brain-derived neurotrophic factor (BDNF) on tissue sparing, neuronal survival, axonal regeneration, and behavioral improvements of the hindlimbs following implantation in the transected adult rat thoracic spinal cord were studied. The foams were embedded in fibrin glue containing acidic-fibroblast growth factor. One group of animals received fibrin glue with acidic-fibroblast growth factor only. The foams were prepared by a thermally induced polymer-solvent phase separation process and contained longitudinally oriented macropores connected to each other by a network of micropores. Both foams and fibrin only resulted in a similar gliotic and inflammatory response in the cord-implant interfaces. With BDNF foam, up to 20% more NeuN-positive cells in the spinal nervous tissue close to the rostral but not caudal spinal cord-implant interface survived than with control foam or fibrin only at 4 and 8 weeks after implantation. Semithin plastic sections and electron microcopy revealed that cells and axons more rapidly invaded BDNF foam than control foam. Also, BDNF foam contained almost twice as many blood vessels than control foam at 8 weeks after implantation. Tissue sparing was similar in all three implantation paradigms; approximately 42% of tissue was spared in the rostral cord and approximately 37% in the caudal cord at 8 weeks post grafting. The number of myelinated and unmyelinated axons was low and not different between the two types of foams. Many more axons were found in the fibrin only graft. Serotonergic axons were not found in any of the implants and none of the axons regenerated into the caudal spinal cord. The behavioral improvements in the hindlimbs were similar in all groups. These findings indicated that foam is well tolerated within the injured spinal cord and that the addition of BDNF promotes cell survival and angiogenesis. However, the overall axonal regeneration response is low. Future research should explore the use of poly(D,L-lactic acid) foams, with or without axonal growth-promoting factors, seeded with Schwann cells to enhance the axonal regeneration and myelination response.
Research center :
Center for Education and Research on Macromolecules (CERM)
Disciplines :
Materials science & engineering Chemistry
Author, co-author :
Patist, Carla M; University of Miami School of Medicine, USA > The Miami Project to Cure Paralysis
Borgerhoff Mulder, Masha; University of Miami School of Medicine, USA > The Miami Project to Cure Paralysis
Gautier, Sandrine; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Maquet, Véronique; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Jérôme, Robert ; Université de Liège - ULiège > Department of Chemistry > Center for Education and Research on Macromolecules (CERM)
Oudega, Martin; University of Miami School of Medicine, USA > Department of Neurological Surgery > The Miami Project to Cure Paralysis
Language :
English
Title :
Freeze-dried poly(D,L-lactic acid) macroporous guidance scaffolds impregnated with brain-derived neurotrophic factor in the transected adult rat thoracic spinal cord
BELSPO - SPP Politique scientifique - Service Public Fédéral de Programmation Politique scientifique F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] The Prinses Beatrix Fonds The Daniel Heumann Foundation Florida State The Miami project
Commentary :
The authors acknowledge Biomaterials (Elsevier) for allowing them to archive this paper.
Dusart I., Schwab M.E. Secondary cell death and the inflammatory reaction after dorsal hemisection of the rat spinal cord. Eur J Neurosci. 6(5):1994;712-724.
Tator C.H. Update on the pathphysiology and pathology of acute spinal cord injury. Brain Pathol. 5(4):1995;407-413.
Tator C.H., Fehlings M.G. Review of the secondary injury theory of spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 75:1991;15-26.
Bunge R.P., Puckett W.R., Hiester E.D. Observations on the pathology of several types of human spinal cord injury, with emphasis on the astrocyte response to penetrating injuries. Adv Neurol. 72:1997;305-315.
Tuszynski M.H., Gabriel K., Gerhardt K., Szollar S. Human spinal cord retains substantial structural mass in chronic stages after injury. J Neurotrauma. 16:1999;523-531.
Bunge M.B. Bridging areas of injury in the spinal cord. Neuroscientist. 7:2001;325-339.
Ramón-Cueto A. Olfactory ensheathing glia transplantation into the injured spinal cord. Prog Brain Res. 128:2000;265-272.
Jones L.L., Oudega M., Bunge M.B., Tuszynski M.H. Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury. J Physiol. 533:2001;83-89.
Takami T., Oudega M., Bates M.L., Wood P.M., Kleitman N., Bunge M.B. Schwann cell but not olfactory ensheathing glia transplants improve hindlimb locomotor performance in the moderately contused adult rat spinal cord. J Neurosci. 22(15):2002;6670-6681.
Plant GW, Christensen CL, Oudega M, Bunge MB. Delayed transplantation of olfactory ensheathing glia promotes sparing/regeneration of supraspinal axons in the contused adult rat spinal cord. J Neurotrauma 2003;20(1):
Cheng H., Cao Y., Olson L. Spinal cord repair in adult paraplegic rats. partial restoration of hindlimb function Science. 273:1996;510-513.
Grill R., Murai K., Blesch A., Gage F.H., Tuszynski M.H. Cellular delivery of neurotrophin-3 promotes corticospinal axonal growth and partial functional recovery after spinal cord injury. J Neurosci. 17:1997;5560-5572.
Ramón-Cueto A., Cordero M.I., Santos-Benito F.F., Avila J. Functional recovery of paraplegic rats and motor axon regeneration in their spinal cords by olfactory ensheathing glia. Neuron. 25:2000;425-435.
Iwashita Y., Kawaguchi S., Murata M. Restoration of function by replacement of spinal cord segments in the rat. Nature. 367:1994;167-170.
Li Y., Field P.M., Raisman G. Repair of adult rat corticospinal tract by transplants of olfactory ensheathing cells. Science. 277:1997;2000-2002.
Liu Y., Kim D., Himes B.T., Chow S.Y., Schallert T., Murray M., Tessler A., Fischer I. Transplants of fibroblasts genetically modified to express BDNF promote regeneration of adult rat rubrospinal axons and recovery of forelimb function. J Neurosci. 19:1999;4370-4387.
McDonald J.W., Liu X.Z., Qu Y., Liu S., Mickey S.K., Turetsky D., Gottlieb D.I., Choi D.W. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 5:1999;1410-1412.
Coumans J.V., Lin T.T., Dai H.N., MacArthur L., McAtee M., Nash C., Bregman B.S. Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins. J Neurosci. 21(23):2001;9334-9344.
Bunge MB, Kleitman N. Neurotrophins and neuroprotection improve axonal regeneration into Schwann cell transplants placed in transected adult rat spinal cord. In: Tuszynski MH, Kordower JH, editors. CNS regeneration. New York: Academic Press; 1998. p. 631-45.
Oudega M., Gautier E.S. Spinal cord repair strategies. Schwann cells, neurotrophic factors, and biodegradable polymers Biomed Rev. 10:1999;75-88.
Oudega M., Sagen J. Spinal cord. Methods of tissue engineering. 2001;1143-1155 Academic Press, New York.
Xu X.M., Guénard V., Kleitman N., Bunge M.B. Axonal regeneration into Schwann cell seeded guidance channels grafted into transected adult rat spinal cord. J Comp Neurol. 351:1995;145-160.
Xu X.M., Chen A., Guénard V., Kleitman N., Bunge M.B. Bridging Schwann cell transplants promote axonal regeneration from both the proximal and caudal stumps of transacted adult rat spinal cord. J Neurocytol. 26:1997;1-16.
Chen A., Xu X.M., Kleitman N., Bunge M.B. Methylprednisolone administration improves axonal regeneration into Schwann cell grafts in transected adult rat thoracic spinal cord. Exp Neurol. 138:1996;261-276.
Xu X.M., Guénard V., Kleitman N., Aebischer P., Bunge M.B. A combination of BDNF and NT-3 promotes supraspinal axonal regeneration into Schwann cell grafts in adult rat thoracic spinal cord. Exp Neurol. 134:1995;261-272.
Oudega M., Xu X.M., Guénard V., Kleitman N., Bunge M.B. A combination of insulin-like growth factor-I and platelet-derived growth factor enhances myelination but diminishes axonal regeneration into Schwann cell grafts in the adult rat spinal cord. Glia. 19:1997;247-258.
Menei P., Montero-Menei C., Whittemore S.R., Bunge R.P., Bunge M.B. Schwann cells genetically modified to secrete human BDNF promote enhanced axonal regrowth across transected adult rat spinal cord. Eur J Neurosci. 10(2):1998;607-621.
Gautier S.E., Oudega M., Fragoso M., Chapon P., Plant G.W., Bunge M.B., Parel J-.M. Poly(α-hydroxyacids for application in the spinal cord. resorbability and biocompatibility with adult rat Schwann cells and spinal cord J Biomed Mater Res. 42:1998;642-654.
Oudega M., Gautier S.E., Chapon P., Fragoso M., Bates M.L., Parel J-.M., Bunge M.B. Axonal regeneration into Schwann cell grafts within resorbable poly(α-hydroxyacid) guidance channels in the adult rat spinal cord. Biomaterials. 22:2001;1125-1136.
Woerly S., Doan V.D., Evans-Martin F., Paramore C.G., Peduzzi J.D. Spinal cord reconstruction using NeuroGel implants and functional recovery after chronic injury. J Neurosci Res. 66(6):2001;1187-1197.
Friedman J.A., Windebank A.J., Moore M.J., Spinner R.J., Currier B.L., Yaszemski M.J. Biodegradable polymer grafts for surgical repair of the injured spinal cord. Neurosurgery. 51(3):2002;742-751.
Teng Y.D., Lavik E.B., Qu X., Park K.I., Ourednik J., Zurakowski D., Langer R., Snyder E.Y. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci USA. 99(5):2002;3024-3029.
Maquet V., Martin D., Malgrange B., Franzen R., Schoenen J., Moonen G., Jérôme R. Peripheral nerve regeneration using bioresorbable macroporous polylactide scaffolds. J Biomed Mater Res. 52(4):2000;639-651.
Maquet V., Martin D., Scholtes F., Franzen R., Schoenen J., Moonen G., Jerome R. Poly(D,L-lactide) foams modified by poly(ethylene oxide)-block-poly(D, L-lactide) copolymers and a-FGF. in vitro and in vivo evaluation for spinal cord regeneration Biomaterials. 22:2001;1137-1146.
Blacher S., Maquet V., Schils F., Martin D., Schoenen J., Moonen G., Jerome R., Pirard J-.P. Image analysis of the axonal ingrowth into poly(D,L-lactide) porous scaffolds in relation to the 3-D porous structure. Biomaterials. 24(6):2003;1033-1044.
Diener P.S., Bregman B.S. Neurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats. Neuroreport. 5(15):1994;1913-1917.
Novikova L., Novikov L., Kellerth J.O. Brain-derived neurotrophic factor reduces necrotic zone and supports neuronal survival after spinal cord hemisection in adult rats. Neurosci Lett. 220(3):1996;203-206.
Yuan Q., Wu W., So K.F., Cheung A.L., Prevette D.M., Oppenheim R.W. Effects of neurotrophic factors on motor neuron survival following axonal injury in newborn rats. Neuroreport. 11(10):2000;2237-2241.
Novikova L.N., Novikov L.N., Kellerth J.O. Differential effects of neurotrophins on neuronal survival and axonal regeneration after spinal cord injury in adult rats. J Comp Neurol. 452(3):2002;255-263.
Bregman B.S., McAtee M., Dai H.N., Kuhn P.L. Neurotrophic factors increase axonal growth after spinal cord injury and transplantation in the adult rat. Exp Neurol. 148(2):1997;475-494.
Oudega M., Hagg T. Neurotrophins promote regeneration of sensory axons in the adult rat spinal cord. Br Res. 818:1999;431-438.
Jin Y., Fischer I., Tessler A., Houle J.D. Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury. Exp Neurol. 177(1):2002;265-275.
Teng Y.D., Mocchetti I., Wrathall J.R. Basic and acidic fibroblast growth factors protect spinal motor neurons in vivo after experimental spinal cord injury. Eur J Neurosci. 10(2):1998;798-802.
Lee Y.S., Baratta J., Yu J., Lin V.W., Robertson R.T. AFGF promotes axonal growth in rat spinal cord organotypic slice co-cultures. J Neurotrauma. 19(3):2002;357-367.
Mullen R.J., Buck C.R., Smith A.M. NeuN, a neuronal specific nuclear protein in vertebrates. Develop. 116(1):1992;201-211.
Beattie M.S., Farooqui A.A., Bresnahan J.C. Review of current evidence for apoptosis after spinal cord injury. J Neurotrauma. 17(10):2000;915-925.
Beattie M.S., Hermann G.E., Rogers R.C., Bresnahan J.C. Cell death in models of spinal cord injury. Prog Brain Res. 137:2002;37-47.
Egea J., Espinet C., Soler R.M., Dolcet X., Yuste V.J., Encinas M., Iglesias M., Rocamora N., Comella J.X. Neuronal survival induced by neurotrophins requires calmodulin. J Cell Biol. 154(3):2001;585-598.
Cheng A., Wang S., Yang D., Xiao R., Mattson M.P. Calmodulin mediates brain-derived neurotrophic factor cell survival signaling upstream of Akt kinase in embryonic neocortical neurons. J Biol Chem. 278(9):2003;7591-7599.
Koda M., Murakami M., Ino H., Yoshinaga K., Ikeda O., Hashimoto M., Yamazaki M., Nakayama C., Moriya H. Brain-derived neurotrophic factors suppress delayed apoptosis of oligodendrocytes after spinal cord injury in rats. J Neurotrauma. 19(6):2002;777-785.
Qiu J., Nesic O., Ye Z., Rea H., Westlund K.N., Xu G.Y., McAdoo D., Hulsebosch C.E., Perez-Polo J.R. Bcl-xL expression after contusion to the rat spinal cord. J Neurotrauma. 18(11):2001;1267-1278.
Sayer F.T., Oudega M., Hagg T. Neurotrophins reduce degeneration of injured ascending sensory and corticospinal motor axons in adult rat spinal cord. Exp Neurol. 175(1):2002;282-296.
Kao C.C., Chnag L.W., Bloodworth J.M. Electron microscopic observations of the mechanisms of terminal club formation in transected spinal cord axons. J Neuropathol Exp Neurol. 36:1977;140-156.
Kao C.C., Chnag L.W., Bloodworth J.M. The mechanisms of spinal cord cavitation following spinal cord transection. Part 2. Electron microscopic observations. J Neurosurg. 46:1977;745-756.
Plant G.W., Bates M.L., Bunge M.B. Inhibitory proteoglycan immunoreactivity is higher at the caudal than the rostral Schwann cell graft-transected spinal cord interface. Mol Cell Neurosci. 17(3):2001;471-487.
Wallace M.C., Tator C.H. Spinal cord blood flow measured with microspheres following spinal cord injury in the cat. Can J Neurol Sci. 13:1986;91-96.
Imperato-Kalmar E.L., McKinney R.A., Schnell L., Rubin B.P., Schwab M.E. Local changes in vascular architecture following partial spinal cord lesion in the rat. Exp Neurol. 145:1997;322-328.
Koyanagi I., Tator C.H., Theriault E. Silicone rubber microangiography of acute spinal cord injury in the rat. Neurosurg. 32:1993;260-268.
Nakahashi T., Fujimura H., Altar C.A., Li J., Kambayashi J., Tandon N.N., Sun B. Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett. 470(2):2000;113-117.
Donovan M.J., Lin M.I., Weign P., Ringstedt T., Kraemer R., Hahn R., Wang S., Ibanez C.F., Rafii S., Hempstead B.L. Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development. 127(21):2000;4531-4540.
Xue L., Greisler H.P. Angiogenic effect of fibroblast growth factor-1 and vascular endothelial factor and their synergism in a novel in vitro quantitative fibrin-based 3-dimensional angiogenesis system. Surgery. 132(2):2002;259-267.
Robinson G.A., Madison R.D. Survival of adult rat retinal ganglion cells with regrown axons in peripheral nerve grafts. a comparison of graft attachment with suture of fibrin glue J Neurosurg. 93(2):2000;275-278.
Guest J.D., Hesse D., Schnell L., Schwab M.E., Bunge M.B., Bunge R.P. Influence of IN-1 antibody and acidic FGF-fibrin glue on the response of injured corticospinal tract axons to human Schwann cell grafts. J Neurosci Res. 50(5):1997;888-905.
Lee Y.S., Hsiao I., Lin V.W. Peripheral nerve grafts and aFGF restore partial hindlimb function in adult paraplegic rats. J Neurotrauma. 19(10):2002;1203-1216.
Maquet V., Blacher S., Pirard R., Pirard J-.P., Jérôme R. Characterization of porous polylactide foams by image analysis and impedance spectroscopy. Langmuir. 16:2000;10463-10470.
Basso D.M., Beattie M.S., Bresnahan J.C. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 12:1995;1-21.
Basso D.M., Beattie M.S., Bresnahan J.C. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection. Exp Neurol. 139:1996;244-256.
