Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury

Bin Yu , Xiaosong Gu

Front. Med. ›› 2019, Vol. 13 ›› Issue (2) : 131 -137.

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Front. Med. ›› 2019, Vol. 13 ›› Issue (2) : 131 -137. DOI: 10.1007/s11684-018-0642-z
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Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury

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Abstract

The inhibitory environment that surrounds the lesion site and the lack of intrinsic regenerative capacity of the adult mammalian central nervous system (CNS) impede the regrowth of injured axons and thereby the reestablishment of neural circuits required for functional recovery after spinal cord injuries (SCI). To circumvent these barriers, biomaterial scaffolds are applied to bridge the lesion gaps for the regrowing axons to follow, and, often by combining stem cell transplantation, to enable the local environment in the growth-supportive direction. Manipulations, such as the modulation of PTEN/mTOR pathways, can also enhance intrinsic CNS axon regrowth after injury. Given the complex pathophysiology of SCI, combining biomaterial scaffolds and genetic manipulation may provide synergistic effects and promote maximal axonal regrowth. Future directions will primarily focus on the translatability of these approaches and promote therapeutic avenues toward the functional rehabilitation of patients with SCIs.

Keywords

spinal cord injury / biomaterial / extrinsic barrier / intrinsic regeneration capacity

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Bin Yu, Xiaosong Gu. Combination of biomaterial transplantation and genetic enhancement of intrinsic growth capacities to promote CNS axon regeneration after spinal cord injury. Front. Med., 2019, 13(2): 131-137 DOI:10.1007/s11684-018-0642-z

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References

[1]

Raineteau O, Schwab ME. Plasticity of motor systems after incomplete spinal cord injury. Nat Rev Neurosci 2001; 2(4): 263–273

[2]

Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci 2014; 15(6): 394–409

[3]

David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci 2011; 12(7): 388–399

[4]

Taoka Y, Okajima K, Uchiba M, Murakami K, Kushimoto S, Johno M, Naruo M, Okabe H, Takatsuki K. Role of neutrophils in spinal cord injury in the rat. Neuroscience 1997; 79(4): 1177–1182

[5]

Popovich PG, Guan Z, McGaughy V, Fisher L, Hickey WF, Basso DM. The neuropathological and behavioral consequences of intraspinal microglial/macrophage activation. J Neuropathol Exp Neurol 2002; 61(7): 623–633

[6]

Fleming JC, Norenberg MD, Ramsay DA, Dekaban GA, Marcillo AE, Saenz AD, Pasquale-Styles M, Dietrich WD, Weaver LC. The cellular inflammatory response in human spinal cords after injury. Brain 2006; 129(Pt 12): 3249–3269

[7]

Beattie MS. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med 2004; 10(12): 580–583

[8]

Schwartz M. Macrophages and microglia in central nervous system injury: are they helpful or harmful? J Cereb Blood Flow Metab 2003; 23(4): 385–394

[9]

Jones TB, Hart RP, Popovich PG. Molecular control of physiological and pathological T-cell recruitment after mouse spinal cord injury. J Neurosci 2005; 25(28): 6576–6583

[10]

Gonzalez R, Glaser J, Liu MT, Lane TE, Keirstead HS. Reducing inflammation decreases secondary degeneration and functional deficit after spinal cord injury. Exp Neurol 2003; 184(1): 456–463

[11]

Bauchet L, Lonjon N, Perrin FE, Gilbert C, Privat A, Fattal C. Strategies for spinal cord repair after injury: a review of the literature and information. Ann Phys Rehabil Med 2009; 52(4): 330–351

[12]

Yiu G, He Z. Glial inhibition of CNS axon regeneration. Nat Rev Neurosci 2006; 7(8): 617–627

[13]

Silver J, Schwab ME, Popovich PG. Central nervous system regenerative failure: role of oligodendrocytes, astrocytes, and microglia. Cold Spring Harb Perspect Biol 2015; 7(3): a020602

[14]

Schwab ME, Strittmatter SM. Nogo limits neural plasticity and recovery from injury. Curr Opin Neurobiol 2014; 27: 53–60

[15]

Grumet M, Flaccus A, Margolis RU. Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules. J Cell Biol 1993; 120(3): 815–824

[16]

Fitch MT, Doller C, Combs CK, Landreth GE, Silver J. Cellular and molecular mechanisms of glial scarring and progressive cavitation: in vivo and in vitro analysis of inflammation-induced secondary injury after CNS trauma. J Neurosci 1999; 19(19): 8182–8198

[17]

Snow DM, Lemmon V, Carrino DA, Caplan AI, Silver J. Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 1990; 109(1): 111–130

[18]

McKeon RJ, Höke A, Silver J. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol 1995; 136(1): 32–43

[19]

Rhodes KE, Raivich G, Fawcett JW. The injury response of oligodendrocyte precursor cells is induced by platelets, macrophages and inflammation-associated cytokines. Neuroscience 2006; 140(1): 87–100

[20]

Ughrin YM, Chen ZJ, Levine JM. Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. J Neurosci 2003; 23(1): 175–186

[21]

Anderson MA, Burda JE, Ren Y, Ao Y, O’Shea TM, Kawaguchi R, Coppola G, Khakh BS, Deming TJ, Sofroniew MV. Astrocyte scar formation aids central nervous system axon regeneration. Nature 2016; 532(7598): 195–200

[22]

Gaudet AD, Popovich PG. Extracellular matrix regulation of inflammation in the healthy and injured spinal cord. Exp Neurol 2014; 258: 24–34

[23]

Shrestha B, Coykendall K, Li Y, Moon A, Priyadarshani P, Yao L. Repair of injured spinal cord using biomaterial scaffolds and stem cells. Stem Cell Res Ther 2014; 5(4): 91

[24]

Joosten EAJ, Bär PR, Gispen WH. Collagen implants and cortico-spinal axonal growth after mid-thoracic spinal cord lesion in the adult rat. J Neurosci Res 1995; 41(4): 481–490

[25]

Han Q, Jin W, Xiao Z, Ni H, Wang J, Kong J, Wu J, Liang W, Chen L, Zhao Y, Chen B, Dai J. The promotion of neural regeneration in an extreme rat spinal cord injury model using a collagen scaffold containing a collagen binding neuroprotective protein and an EGFR neutralizing antibody. Biomaterials 2010; 31(35): 9212–9220

[26]

Liu T, Houle JD, Xu J, Chan BP, Chew SY. Nanofibrous collagen nerve conduits for spinal cord repair. Tissue Eng Part A 2012; 18(9-10): 1057–1066

[27]

Han S, Wang B, Jin W, Xiao Z, Li X, Ding W, Kapur M, Chen B, Yuan B, Zhu T, Wang H, Wang J, Dong Q, Liang W, Dai J. The linear-ordered collagen scaffold-BDNF complex significantly promotes functional recovery after completely transected spinal cord injury in canine. Biomaterials 2015; 41: 89–96

[28]

Spilker MH, Yannas IV, Kostyk SK, Norregaard TV, Hsu HP, Spector M. The effects of tubulation on healing and scar formation after transection of the adult rat spinal cord. Restor Neurol Neurosci 2001; 18(1): 23–38

[29]

Lewandowski G, Steward O. AAV shRNA-mediated suppression of PTEN in adult rats in combination with salmon fibrin administration enables regenerative growth of corticospinal axons and enhances recovery of voluntary motor function after cervical spinal cord injury. J Neurosci 2014; 34(30): 9951–9962

[30]

Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury. Cell 2012; 150(6): 1264–1273

[31]

Lu P, Woodruff G, Wang Y, Graham L, Hunt M, Wu D, Boehle E, Ahmad R, Poplawski G, Brock J, Goldstein LS, Tuszynski MH. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 2014; 83(4): 789–796

[32]

Kadoya K, Lu P, Nguyen K, Lee-Kubli C, Kumamaru H, Yao L, Knackert J, Poplawski G, Dulin JN, Strobl H, Takashima Y, Biane J, Conner J, Zhang SC, Tuszynski MH. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 2016; 22(5): 479–487

[33]

Li X, Yang Z, Zhang A, Wang T, Chen W. Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats. Biomaterials 2009; 30(6): 1121–1132

[34]

Yang Z, Zhang A, Duan H, Zhang S, Hao P, Ye K, Sun YE, Li X. NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury. Proc Natl Acad Sci U S A 2015; 112(43): 13354–13359

[35]

Duan H, Ge W, Zhang A, Xi Y, Chen Z, Luo D, Cheng Y, Fan KS, Horvath S, Sofroniew MV, Cheng L, Yang Z, Sun YE, Li X. Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury. Proc Natl Acad Sci U S A 2015; 112(43): 13360–13365

[36]

Stokols S, Sakamoto J, Breckon C, Holt T, Weiss J, Tuszynski MH. Templated agarose scaffolds support linear axonal regeneration. Tissue Eng 2006; 12(10): 2777–2787

[37]

Gros T, Sakamoto JS, Blesch A, Havton LA, Tuszynski MH. Regeneration of long-tract axons through sites of spinal cord injury using templated agarose scaffolds. Biomaterials 2010; 31(26): 6719–6729

[38]

Gao M, Lu P, Bednark B, Lynam D, Conner JM, Sakamoto J, Tuszynski MH. Templated agarose scaffolds for the support of motor axon regeneration into sites of complete spinal cord transection. Biomaterials 2013; 34(5): 1529–1536

[39]

Lee JK, Chan AF, Luu SM, Zhu Y, Ho C, Tessier-Lavigne M, Zheng B. Reassessment of corticospinal tract regeneration in Nogo-deficient mice. J Neurosci 2009; 29(27): 8649–8654

[40]

Lee JK, Geoffroy CG, Chan AF, Tolentino KE, Crawford MJ, Leal MA, Kang B, Zheng B. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 2010; 66(5): 663–670

[41]

Goldberg JL, Klassen MP, Hua Y, Barres BA. Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells. Science 2002; 296(5574): 1860–1864

[42]

Cai D, Qiu J, Cao Z, McAtee M, Bregman BS, Filbin MT. Neuronal cyclic AMP controls the developmental loss in ability of axons to regenerate. J Neurosci 2001; 21(13): 4731–4739

[43]

Hao Y, Frey E, Yoon C, Wong H, Nestorovski D, Holzman LB, Giger RJ, DiAntonio A, Collins C. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. eLife 2016; 5: e14048

[44]

Moore DL, Blackmore MG, Hu Y, Kaestner KH, Bixby JL, Lemmon VP, Goldberg JL. KLF family members regulate intrinsic axon regeneration ability. Science 2009; 326(5950): 298–301

[45]

Blackmore MG, Wang Z, Lerch JK, Motti D, Zhang YP, Shields CB, Lee JK, Goldberg JL, Lemmon VP, Bixby JL. Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract. Proc Natl Acad Sci U S A 2012; 109(19): 7517–7522

[46]

Norsworthy MW, Bei F, Kawaguchi R, Wang Q, Tran NM, Li Y, Brommer B, Zhang Y, Wang C, Sanes JR, Coppola G, He Z. Sox11 expression promotes regeneration of some retinal ganglion cell types but kills others. Neuron 2017; 94(6): 1112–1120.e4

[47]

Park KK, Liu K, Hu Y, Smith PD, Wang C, Cai B, Xu B, Connolly L, Kramvis I, Sahin M, He Z. Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 2008; 322(5903): 963–966

[48]

Belin S, Nawabi H, Wang C, Tang S, Latremoliere A, Warren P, Schorle H, Uncu C, Woolf CJ, He Z, Steen JA. Injury-induced decline of intrinsic regenerative ability revealed by quantitative proteomics. Neuron 2015; 86(4): 1000–1014

[49]

Liu K, Lu Y, Lee JK, Samara R, Willenberg R, Sears-Kraxberger I, Tedeschi A, Park KK, Jin D, Cai B, Xu B, Connolly L, Steward O, Zheng B, He Z. PTEN deletion enhances the regenerative ability of adult corticospinal neurons. Nat Neurosci 2010; 13(9): 1075–1081

[50]

Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13(5): 283–296

[51]

Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, He Z. Sustained axon regeneration induced by co-deletion of PTEN and SOCS3. Nature 2011; 480(7377): 372–375

[52]

Duan X, Qiao M, Bei F, Kim IJ, He Z, Sanes JR. Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling. Neuron 2015; 85(6): 1244–1256

[53]

Liu Y, Wang X, Li W, Zhang Q, Li Y, Zhang Z, Zhu J, Chen B, Williams PR, Zhang Y, Yu B, Gu X, He Z. A sensitized IGF1 treatment restores corticospinal axon-dependent functions. Neuron 2017; 95(4): 817–833.e4

[54]

Bei F, Lee HHC, Liu X, Gunner G, Jin H, Ma L, Wang C, Hou L, Hensch TK, Frank E, Sanes JR, Chen C, Fagiolini M, He Z. Restoration of visual function by enhancing conduction in regenerated axons. Cell 2016; 164(1-2): 219–232

[55]

Lu P, Woodruff G, Wang Y, Graham L, Hunt M, Wu D, Boehle E, Ahmad R, Poplawski G, Brock J, Goldstein LSB, Tuszynski MH. Long-distance axonal growth from human induced pluripotent stem cells after spinal cord injury. Neuron 2014; 83(4): 789–796

[56]

Kadoya K, Lu P, Nguyen K, Lee-Kubli C, Kumamaru H, Yao L, Knackert J, Poplawski G, Dulin JN, Strobl H, Takashima Y, Biane J, Conner J, Zhang SC, Tuszynski MH. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 2016; 22(5): 479–487

[57]

García-Alías G, Barkhuysen S, Buckle M, Fawcett JW. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci 2009; 12(9): 1145–1151

[58]

Lang BT, Cregg JM, DePaul MA, Tran AP, Xu K, Dyck SM, Madalena KM, Brown BP, Weng YL, Li S, Karimi-Abdolrezaee S, Busch SA, Shen Y, Silver J. Modulation of the proteoglycan receptor PTPs promotes recovery after spinal cord injury. Nature 2015; 518(7539): 404–408

[59]

Lim JH, Stafford BK, Nguyen PL, Lien BV, Wang C, Zukor K, He Z, Huberman AD. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 2016; 19(8): 1073–1084

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