Application of stem cells in peripheral nerve regeneration

Sheng Yi , Yu Zhang , Xiaokun Gu , Li Huang , Kairong Zhang , Tianmei Qian , Xiaosong Gu

Burns & Trauma ›› 2020, Vol. 8 ›› Issue (1) : tkaa002

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Burns & Trauma ›› 2020, Vol. 8 ›› Issue (1) :tkaa002 DOI: 10.1093/burnst/tkaa002
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Application of stem cells in peripheral nerve regeneration
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Abstract

Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity. The severity of peripheral nerve injury can be classified as neurapraxia, axonotmesis or neurotmesis, according to Seddon’s classification, or five different degrees according to Sunderland’s classification. Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects. The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties, including donor nerve sacrifice and nerve mismatch. Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects. The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process. Numerous stem cells, including embryonic stem cells, neural stem cells, bone marrow mesenchymal stem cells, adipose stem cells, skin-derived precursor stem cells and induced pluripotent stem cells, have been used in neural tissue engineering. In the current review, recent trials of stem cell-based tissue-engineered nerve grafts have been summarized; potential concerns and perspectives of stem cell therapeutics have also been contemplated.

Keywords

Peripheral nerve injury / Tissue-engineered nerve grafts / Seed cells / Stem cells / Peripheral nerve regeneration

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Sheng Yi, Yu Zhang, Xiaokun Gu, Li Huang, Kairong Zhang, Tianmei Qian, Xiaosong Gu. Application of stem cells in peripheral nerve regeneration. Burns & Trauma, 2020, 8 (1) : tkaa002 DOI:10.1093/burnst/tkaa002

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References

[1]

Asplund M, Nilsson M, Jacobsson A, von Holst H. Incidence of traumatic peripheral nerve injuries and amputations in Sweden between 1998 and 2006. Neuroepidemiology. 2009; 32: 217-28.

[2]

Li R, Liu Z, Pan Y, Chen L, Zhang Z, Lu L. Peripheral nerve injuries treatment: A systematic review. Cell Biochem Biophys. 2014; 68: 449-54.

[3]

Martyn CN, Hughes RA. Epidemiology of peripheral neuropathy. J Neurol Neurosurg Psychiatry. 1997; 62: 310-8.

[4]

Evans GR. Peripheral nerve injury: A review and approach to tissue engineered constructs. Anat Rec. 2001; 263: 396-404.

[5]

Tian L, Prabhakaran MP, Ramakrishna S. Strategies for regeneration of components of nervous system: Scaffolds, cells and biomolecules. Regen Biomater. 2015; 2: 31-45.

[6]

Schmidt CE, Leach JB. Neural tissue engineering: Strategies for repair and regeneration. Annu Rev Biomed Eng. 2003; 5: 293-347.

[7]

Kaya Y, Sarikcioglu L. Sir Herbert Seddon (1903-1977) and his classification scheme for peripheral nerve injury. Childs Nerv Syst. 2015; 31: 177-80.

[8]

Robinson LR. Traumatic injury to peripheral nerves. Muscle Nerve. 2000; 23: 863-73.

[9]

Sunderland S.A classification of peripheral nerve injuries producing loss of function. Brain. 1951; 74: 491-516.

[10]

Sullivan R, Dailey T, Duncan K, Abel N, Borlongan CV. Peripheral nerve injury: Stem cell therapy and peripheral nerve transfer. Int J Mol Sci. 2016; 17: 2101.

[11]

Caillaud M, Richard L, Vallat JM, Desmouliere A, Billet F. Peripheral nerve regeneration and intraneural revascularization. Neural Regen Res. 2019; 14: 24-33.

[12]

Gu X, Ding F, Yang Y, Liu J. Construction of tissue engineered nerve grafts and their application in peripheral nerve regeneration. Prog in Neurobiol. 2011; 93: 204-30.

[13]

Wong ML, Griffiths LG. Immunogenicity in xenogeneic scaffold generation: Antigen removal vs. decellularization. Acta Biomater. 2014; 10: 1806-16.

[14]

Gu X, Ding F, Williams DF. Neural tissue engineering options for peripheral nerve regeneration. Biomaterials. 2014; 35: 6143-56.

[15]

Yi S, Xu L, Gu X. Scaffolds for peripheral nerve repair and reconstruction. Exp Neurol. 2019; 319: 112761.

[16]

Jones S, Eisenberg HM, Jia X. Advances and future applications of augmented peripheral nerve regeneration. Int J Mol Sci. 2016; 17: E1494.

[17]

Ren Z, Wang Y, Peng J, Zhao Q, Lu S. Role of stem cells in the regeneration and repair of peripheral nerves. Rev Neurosci. 2012; 23: 135-43.

[18]

Jessen KR, Mirsky R, Lloyd AC. Schwann cells: Development and role in nerve repair. Cold Spring Harb Perspect Biol. 2015; 7:a020487.

[19]

Painter MW. Aging Schwann cells: Mechanisms, implications, future directions. Curr Opin Neurobiol. 2017; 47: 203-8.

[20]

Brushart TM, Aspalter M, Griffin JW, Redett R, Hameed H, Zhou C, et al. Schwann cell phenotype is regulated by axon modality and central-peripheral location, and persists in vitro. Exp Neurol. 2013; 247: 272-81.

[21]

Madduri S, Gander B. Schwann cell delivery of neurotrophic factors for peripheral nerve regeneration. J Peripher Nerv Syst. 2010; 15: 93-103.

[22]

Kornfeld T, Vogt PM, Bucan V, Peck CT, Reimers K, Radtke C. Characterization and Schwann cell seeding of up to 15.0 cm long spider silk nerve conduits for reconstruction of peripheral nerve defects. J Funct Biomater. 2016; 7: 30.

[23]

Strauch B, Ferder M, Lovelle-Allen S, Moore K, Kim DJ, Llena J.Determining the maximal length of a vein conduit used as an interposition graft for nerve regeneration. J Reconstructive Microsurg. 1996; 12: 521-7.

[24]

Chiu DT, Strauch B. A prospective clinical evaluation of autogenous vein grafts used as a nerve conduit for distal sensory nerve defects of 3 cm or less. Plast Reconstr Surg. 1990; 86: 928-34.

[25]

Strauch B, Rodriguez DM, Diaz J, Yu HL, Kaplan G, Weinstein DE. Autologous Schwann cells drive regeneration through a 6-cm autogenous venous nerve conduit. J Reconstructive Microsurg. 2001; 17: 589-95 discussion 96-7.

[26]

Carr MJ, Johnston AP. Schwann cells as drivers of tissue repair and regeneration. Curr Opin Neurobiol. 2017; 47: 52-7.

[27]

Dilwali S, Patel PB, Roberts DS, Basinsky GM, Harris GJ, Emerick KS, et al. Primary culture of human Schwann and schwannoma cells: Improved and simplified protocol. Hear Res. 2014; 315: 25-33.

[28]

Casella GT, Bunge RP, Wood PM. Improved method for harvesting human Schwann cells from mature peripheral nerve and expansion in vitro. Glia. 1996; 17: 327-38.

[29]

Zhu C, Huang J, Xue C, Wang Y, Wang S, Bao S, et al. Skin derived precursor Schwann cell-generated acellular matrix modified chitosan/silk scaffolds for bridging rat sciatic nerve gap. Neurosci Res. 2018; 135: 21-31.

[30]

Mosahebi A, Fuller P, Wiberg M, Terenghi G. Effect of allogeneic Schwann cell transplantation on peripheral nerve regeneration. Exp Neurol. 2002; 173: 213-23.

[31]

Ziegler L, Grigoryan S, Yang IH, Thakor NV, Goldstein RS. Efficient generation of schwann cells from human embryonic stem cell-derived neurospheres. Stem Cell Rev Rep. 2011; 7: 394-403.

[32]

Liu Q, Spusta SC, Mi R, Lassiter RN, Stark MR, Hoke A, et al. Human neural crest stem cells derived from human ESCs and induced pluripotent stem cells: Induction, maintenance, and differentiation into functional schwann cells. Stem Cells Transl Med. 2012; 1: 266-78.

[33]

Cui L, Jiang J, Wei L, Zhou X, Fraser JL, Snider BJ, et al. Transplantation of embryonic stem cells improves nerve repair and functional recovery after severe sciatic nerve axotomy in rats. Stem Cells. 2008; 26: 1356-65.

[34]

Jones I, Novikova LN, Novikov LN, Renardy M, Ullrich A, Wiberg M, et al. Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury. J Tissue Eng Regen Med. 2018; 12: e2099-109.

[35]

Jiang L, Jones S, Jia X. Stem cell transplantation for peripheral nerve regeneration: Current options and opportunities. Int J Mol Sci. 2017; 18: 94.

[36]

Rippon HJ, Bishop AE. Embryonic stem cells. Cell Prolif. 2004; 37: 23-34.

[37]

Lee G, Chambers SM, Tomishima MJ, Studer L. Derivation of neural crest cells from human pluripotent stem cells. Nat Protoc. 2010; 5: 688-701.

[38]

Gage FH, Temple S. Neural stem cells: Generating and regenerating the brain. Neuron. 2013; 80: 588-601.

[39]

Wang C, Lu CF, Peng J, Hu CD, Wang Y. Roles of neural stem cells in the repair of peripheral nerve injury. Neural Regen Res. 2017; 12: 2106- 12.

[40]

Zhang H, Wei YT, Tsang KS, Sun CR, Li J, Huang H, et al. Implantation of neural stem cells embedded in hyaluronic acid and collagen composite conduit promotes regeneration in a rabbit facial nerve injury model. J Transl Med. 2008; 6: 67.

[41]

Guo BF, Dong MM. Application of neural stem cells in tissue-engineered artificial nerve. Otolaryngol Head Neck Surg. 2009; 140: 159-64.

[42]

Heine W, Conant K, Griffin JW, Hoke A. Transplanted neural stem cells promote axonal regeneration through chronically denervated peripheral nerves. Exp Neurol. 2004; 189: 231-40.

[43]

Shi Y, Zhou L, Tian J, Wang Y. Transplantation of neural stem cells overexpressing glia-derived neurotrophic factor promotes facial nerve regeneration. Acta Otolaryngol. 2009; 129: 906-14.

[44]

Lee DC, Chen JH, Hsu TY, Chang LH, Chang H, Chi YH, et al. Neural stem cells promote nerve regeneration through IL12-induced Schwann cell differentiation. Mol Cell Neurosci. 2017; 79: 1-11.

[45]

Johnson TS, O’Neill AC, Motarjem PM, Nazzal J, Randolph M, Winograd JM. Tumor formation following murine neural precursor cell transplantation in a rat peripheral nerve injury model. J Reconstr Microsurg. 2008; 24: 545-50.

[46]

Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005; 105: 1815-22.

[47]

Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells 2019; 8: 886.

[48]

Caddick J, Kingham PJ, Gardiner NJ, Wiberg M, Terenghi G. Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage. Glia. 2006; 54: 840-9.

[49]

Yang Y, Yuan X, Ding F, Yao D, Gu Y, Liu J, et al. Repair of rat sciatic nerve gap by a silk fibroin-based scaffold added with bone marrow mesenchymal stem cells. Tissue Eng Part A. 2011; 17: 2231-44.

[50]

Zhao Z, Wang Y, Peng J, Ren Z, Zhan S, Liu Y, et al. Repair of nerve defect with acellular nerve graft supplemented by bone marrow stromal cells in mice. Microsurgery. 2011; 31: 388-94.

[51]

Fan L, Yu Z, Li J, Dang X, Wang K. Schwann-like cells seeded in acellular nerve grafts improve nerve regeneration. BMC Musculoskelet Disord. 2014; 15: 165.

[52]

Cuevas P, Carceller F, Dujovny M, Garcia-Gomez I, Cuevas B, Gonzalez-Corrochano R, et al. Peripheral nerve regeneration by bone marrow stromal cells. Neurol Res. 2002; 24: 634-8.

[53]

Chen CJ, Ou YC, Liao SL, Chen WY, Chen SY, Wu CW, et al. Transplantation of bone marrow stromal cells for peripheral nerve repair. Exp Neurol. 2007; 204: 443-53.

[54]

Ding F, Wu J, Yang Y, Hu W, Zhu Q, Tang X, et al. Use of tissue-engineered nerve grafts consisting of a chitosan/poly(lactic-co-glycolic acid)-based scaffold included with bone marrow mesenchymal cells for bridging 50-mm dog sciatic nerve gaps. Tissue Eng Part A. 2010; 16: 3779-90.

[55]

Muheremu A, Chen L, Wang X, Wei Y, Gong K, Ao Q. Chitosan nerve conduits seeded with autologous bone marrow mononuclear cells for 30 mm goat peroneal nerve defect. Sci Rep. 2017; 7: 44002.

[56]

Wakao S, Hayashi T, Kitada M, Kohama M, Matsue D, Teramoto N, et al. Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration. Exp Neurol. 2010; 223: 537-47.

[57]

Hu N, Wu H, Xue C, Gong Y, Wu J, Xiao Z, et al. Long-term outcome of the repair of 50 mm long median nerve defects in rhesus monkeys with marrow mesenchymal stem cells-containing, chitosan-based tissue engineered nerve grafts. Biomaterials. 2013; 34: 100-11.

[58]

Watanabe Y, Sasaki R, Matsumine H, Yamato M, Okano T. Undifferentiated and differentiated adipose-derived stem cells improve nerve regeneration in a rat model of facial nerve defect. J Tissue Eng Regen Med. 2017; 11: 362-74.

[59]

Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, et al. Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med. 2005; 54: 132-41.

[60]

Xie S, Lu F, Han J, Tao K, Wang H, Simental A, et al. Efficient generation of functional Schwann cells from adipose-derived stem cells in defined conditions. Cell Cycle. 2017; 16: 841-51.

[61]

Tomita K, Madura T, Sakai Y, Yano K, Terenghi G, Hosokawa K. Glial differentiation of human adipose-derived stem cells: Implications for cell-based transplantation therapy. Neuroscience. 2013; 236: 55-65.

[62]

Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G. Adipose-derived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol. 2007; 207: 267-74.

[63]

di Summa PG, Kalbermatten DF, Pralong E, Raffoul W, Kingham PJ, Terenghi G.Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts. Neuroscience. 2011; 181: 278-91.

[64]

Masgutov R, Masgutova G, Mullakhmetova A, Zhuravleva M, Shulman A, Rogozhin A, et al. Adipose-derived mesenchymal stem cells applied in fibrin glue stimulate peripheral nerve regeneration. Front Med (Lausanne). 2019; 6: 68.

[65]

Engels PE, Tremp M, Kingham PJ, di Summa PG, Largo RD, Schaefer DJ, et al. Harvest site influences the growth properties of adipose derived stem cells. Cytotechnology. 2013; 65: 437-45.

[66]

Sowa Y, Imura T, Numajiri T, Nishino K, Fushiki S.Adipose-derived stem cells produce factors enhancing peripheral nerve regeneration: Influence of age and anatomic site of origin. Stem Cells Dev. 2012; 21: 1852-62.

[67]

Tremp M, Meyer Zu Schwabedissen M, Kappos EA, Engels PE, Fischmann A, Scherberich A, et al. The regeneration potential after human and autologous stem cell transplantation in a rat sciatic nerve injury model can be monitored by MRI. Cell Transplant. 2015; 24: 203-11.

[68]

Fernandes KJ, McKenzie IA, Mill P, Smith KM, Akhavan M, Barnabe-Heider F, et al. A dermal niche for multipotent adult skin-derived precursor cells. Nature Cell Biol. 2004; 6: 1082-93.

[69]

Biernaskie JA, McKenzie IA, Toma JG, Miller FD. Isolation of skin-derived precursors (SKPs) and differentiation and enrichment of their Schwann cell progeny. Nat Protoc. 2006; 1: 2803-12.

[70]

McKenzie IA, Biernaskie J, Toma JG, Midha R, Miller FD. Skin-derived precursors generate myelinating Schwann cells for the injured and dysmyelinated nervous system. J Neurosci. 2006; 26: 6651-60.

[71]

Marchesi C, Pluderi M, Colleoni F, Belicchi M, Meregalli M, Farini A, et al. Skin-derived stem cells transplanted into resorbable guides provide functional nerve regeneration after sciatic nerve resection. Glia. 2007; 55: 425-38.

[72]

Park BW, Kang DH, Kang EJ, Byun JH, Lee JS, Maeng GH, et al. Peripheral nerve regeneration using autologous porcine skin-derived mesenchymal stem cells. J Tissue Eng Regen Med. 2012; 6: 113-24.

[73]

Walsh S, Biernaskie J, Kemp SW, Midha R. Supplementation of acellular nerve grafts with skin derived precursor cells promotes peripheral nerve regeneration. Neuroscience. 2009; 164: 1097-107.

[74]

Walsh SK, Gordon T, Addas BM, Kemp SW, Midha R. Skin-derived precursor cells enhance peripheral nerve regeneration following chronic denervation. Exp Neurol. 2010; 223: 221-8.

[75]

Khuong HT, Kumar R, Senjaya F, Grochmal J, Ivanovic A, Shakhbazau A, et al. Skin derived precursor Schwann cells improve behavioral recovery for acute and delayed nerve repair. Exp Neurol. 2014; 254: 168-79.

[76]

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126: 663-76.

[77]

Okita K, Ichisaka T, Yamanaka S. Generation of germline-competent induced pluripotent stem cells. Nature. 2007; 448: 313-7.

[78]

Wang A, Tang Z, Park IH, Zhu Y, Patel S, Daley GQ, et al. Induced pluripotent stem cells for neural tissue engineering. Biomaterials. 2011; 32: 5023- 32.

[79]

Uemura T, Takamatsu K, Ikeda M, Okada M, Kazuki K, Ikada Y, et al. Transplantation of induced pluripotent stem cell-derived neurospheres for peripheral nerve repair. Biochem Biophys Res Commun. 2012; 419: 130-5.

[80]

Uemura T, Ikeda M, Takamatsu K, Yokoi T, Okada M, Nakamura H. Long-term efficacy and safety outcomes of transplantation of induced pluripotent stem cell-derived neurospheres with bioabsorbable nerve conduits for peripheral nerve regeneration in mice. Cells Tissues Organs. 2014; 200: 78-91.

[81]

Ikeda M, Uemura T, Takamatsu K, Okada M, Kazuki K, Tabata Y, et al. Acceleration of peripheral nerve regeneration using nerve conduits in combination with induced pluripotent stem cell technology and a basic fibroblast growth factor drug delivery system. J Biomed Mater Res A. 2014; 102: 1370-8.

[82]

Ouchi T, Morikawa S, Shibata S, Fukuda K, Okuno H, Fujimura T, et al. LNGFR(+)THY-1(+) human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells. Differentiation. 2016; 92: 270-80.

[83]

Kimura H, Ouchi T, Shibata S, Amemiya T, Nagoshi N, Nakagawa T, et al. Stem cells purified from human induced pluripotent stem cell-derived neural crest-like cells promote peripheral nerve regeneration. Sci Rep. 2018; 8: 10071.

[84]

Muhammad A, Kim K, Epifantseva I, Aghamaleky-Sarvestany A, Simpkinson ME, Carmona S, et al. Cell transplantation strategies for acquired and inherited disorders of peripheral myelin. Ann Clin Transl Neurol. 2018; 5: 186-200.

[85]

Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, et al. Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 2008; 26: 101-6.

[86]

Okada M, Yoneda Y. The timing of retroviral silencing correlates with the quality of induced pluripotent stem cell lines. Biochim Biophys Acta. 2011; 1810: 226-35.

[87]

Grimoldi N, Colleoni F, Tiberio F, Vetrano IG, Cappellari A, Costa A, et al. Stem cell salvage of injured peripheral nerve. Cell Transplant. 2015; 24: 213-22.

[88]

Braga-Silva J, Gehlen D, Padoin AV, Machado DC, Garicochea B, Costa da Costa J. Can local supply of bone marrow mononuclear cells improve the outcome from late tubular repair of human median and ulnar nerves? J Hand Surg Eur Vol. 2008; 33: 488-93.

[89]

Lehmann HC, Hoke A. Use of engineered Schwann cells in peripheral neuropathy: Hopes and hazards. Brain Res. 2016; 1638: 97-104.

[90]

Kubo T, Randolph MA, Groger A, Winograd JM. Embryonic stem cell-derived motor neurons form neuromuscular junctions in vitro and enhance motor functional recovery in vivo. Plast Reconstr Surg. 2009; 123: 139S-48S.

[91]

Schaakxs D, Kalbermatten DF, Raffoul W, Wiberg M, Kingham PJ. Regenerative cell injection in denervated muscle reduces atrophy and enhances recovery following nerve repair. Muscle Nerve. 2013; 47: 691-701.

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