The impact of stem cells in neuro-oncology: applications, evidence, limitations and challenges

Sabino Luzzi; Alice  Giotta Lucifero; Ilaria  Brambilla; Chiara Trabatti; Mario Mosconi; Salvatore Savasta; Thomas  Foiadelli

doi:10.23750/abm.v91i7-S.9955

The impact of stem cells in neuro-oncology: applications, evidence, limitations and challenges

Authors

Sabino Luzzi Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; Neurosurgery Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Alice Giotta Lucifero Neurosurgery Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
Ilaria Brambilla Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Uni-versity of Pavia, Pavia, Italy
Chiara Trabatti Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Uni-versity of Pavia, Pavia, Italy
Mario Mosconi c and Traumatology Unit, Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy
Salvatore Savasta Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Uni-versity of Pavia, Pavia, Italy
Thomas Foiadelli Pediatric Clinic, Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, Uni-versity of Pavia, Pavia, Italy

DOI: https://doi.org/10.23750/abm.v91i7-S.9955

Keywords:

Cell-based Therapy; High-Grade Glioma; Neuro-Oncology; Somatic Cell Therapy; Stem Cells.

Abstract

Background: Stem cells (SCs) represent a recent and attractive therapeutic option for neuro-oncology, as well as for treating degenerative, ischemic and traumatic pathologies of the central nervous system. This is mainly because of their homing capacity, which makes them capable of reaching the inaccessible SC niches of the tumor, therefore, acting as living drugs. The target of the study is a comprehensive overview of the SC-based therapies in neuro-oncology, also highlighting the current translational challenges of this type of approach. Methods: An online search of the literature was carried out on the PubMed/MEDLINE and ClinicalTrials.gov websites, restricting it to the most pertinent keywords regarding the systematization of the SCs and their therapeutic use for malignant brain tumors. A large part of the search was dedicated to clinical trials. Only preclinical and clinical data belonging to the last 5 years were shortlisted. A further sorting was implemented based on the best match and relevance. Results: The results consisted in 96 relevant articles and 31 trials. Systematization involves a distinction between human embryonic, fetal and adult, but also totipotent, pluripotent or multipotent SCs. Mesenchymal and neuronal SCs were the most studied for neuro-oncological illnesses. 30% and 50% of the trials were phase I and II, respectively. Conclusion: Mesenchymal and neuronal SCs are ideal candidates for SCs-based therapy of malignant brain tumors. The spectrum of their possible applications is vast and is mainly based on the homing capacity toward the tumor microenvironment. Availability, delivery route, oncogenicity and ethical issues are the main translational challenges concerning the use of SCs in neuro-oncology.

References

de Castro F. Cajal and the Spanish Neurological School: Neuroscience Would Have Been a Different Story Without Them. Front Cell Neurosci. 2019;13: 187. https://doi.org/10.3389/fncel.2019.00187.

De Carlos JA, Pedraza M. Santiago Ramon y Cajal: The Cajal Institute and the Spanish Histological School. Anat Rec (Hoboken). 2014;297(10): 1785-1802. https://doi.org/10.1002/ar.23019.

Berciano J, Lafarga M, Berciano M. Santiago Ramon y Cajal. Neurologia. 2001;16(3): 118-121.

Pascual-Castroviejo I, Lopez-Pereira P, Savasta S, Lopez-Gutierrez JC, Lago CM, Cisternino M. Neurofibromatosis type 1 with external genitalia involvement presentation of 4 patients. J Pediatr Surg. 2008;43(11): 1998-2003. https://doi.org/10.1016/j.jpedsurg.2008.01.074.

Savasta S, Chiapedi S, Perrini S, Tognato E, Corsano L, Chiara A. Pai syndrome: a further report of a case with bifid nose, lipoma, and agenesis of the corpus callosum. Childs Nerv Syst. 2008;24(6): 773-776. https://doi.org/10.1007/s00381-008-0613-9.

Parisi P, Vanacore N, Belcastro V, et al. Clinical guidelines in pediatric headache: evaluation of quality using the AGREE II instrument. J Headache Pain. 2014;15: 57. https://doi.org/10.1186/1129-2377-15-57.

Salpietro V, Mankad K, Kinali M, et al. Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study. J Pediatr Endocrinol Metab. 2014;27(1-2): 107-115. https://doi.org/10.1515/jpem-2013-0156.

Foiadelli T, Piccorossi A, Sacchi L, et al. Clinical characteristics of headache in Italian adolescents aged 11-16 years: a cross-sectional questionnaire school-based study. Ital J Pediatr. 2018;44(1): 44. https://doi.org/10.1186/s13052-018-0486-9.

Garone G, Reale A, Vanacore N, et al. Acute ataxia in paediatric emergency departments: a multicentre Italian study. Arch Dis Child. 2019;104(8): 768-774. https://doi.org/10.1136/archdischild-2018-315487.

Nosadini M, Granata T, Matricardi S, et al. Relapse risk factors in anti-N-methyl-D-aspartate receptor encephalitis. Dev Med Child Neurol. 2019;61(9): 1101-1107. https://doi.org/10.1111/dmcn.14267.

Shyh-Chang N, Ng HH. The metabolic programming of stem cells. Genes Dev. 2017;31(4): 336-346. https://doi.org/10.1101/gad.293167.116.

Laplane L, Solary E. Towards a classification of stem cells. Elife. 2019;8. https://doi.org/10.7554/eLife.46563.

Challenging Stem Cells. Cell. 2018;173(5): 1063-1065. https://doi.org/10.1016/j.cell.2018.05.010.

Pourquié O. Human embryonic stem cells get organized. Nature. 2018;558(7708): 35-36. https://doi.org/10.1038/d41586-018-05115-y.

Baumann K. Stem cells: A key to totipotency. Nat Rev Mol Cell Biol. 2017;18(3): 137. https://doi.org/10.1038/nrm.2017.9.

Vivanco Mdel M. Mammary Stem Cells. Preface. Methods Mol Biol. 2015;1293: v-vi. https://doi.org/10.1007/978-1-4939-2519-3.

Kawasaki T, Yu RK. Special issue: Glycobiology on stem cells ---editorial. Glycoconj J. 2017;34(6): 691. https://doi.org/10.1007/s10719-017-9803-6.

Zheng L. Editorial: Epigenetic Regulation on Stem Cells Fate and Regeneration. Curr Stem Cell Res Ther. 2018;13(1): 3. https://doi.org/10.2174/1574888x1301171227105835.

Wrighton KH. Stem cells: The different flavours of iPS cells. Nat Rev Genet. 2017;18(7): 394. https://doi.org/10.1038/nrg.2017.42.

Maraldi T, Angeloni C, Giannoni E, Sell C. Reactive Oxygen Species in Stem Cells. Oxid Med Cell Longev. 2015;2015: 159080. https://doi.org/10.1155/2015/159080.

Yamashita YM. Cell biology of stem cells: studying stem cells at the level of cell biology and studying cell biology using stem cells. Mol Biol Cell. 2018;29(24): 2912. https://doi.org/10.1091/mbc.E18-09-0596.

Luzzi S, Crovace AM, Del Maestro M, et al. The cell-based approach in neurosurgery: ongoing trends and future perspectives. Heliyon. 2019;5(11). https://doi.org/10.1016/j.heliyon.2019.e02818.

Damdimopoulou P, Rodin S, Stenfelt S, Antonsson L, Tryggvason K, Hovatta O. Human embryonic stem cells. Best Pract Res Clin Obstet Gynaecol. 2016;31: 2-12. https://doi.org/10.1016/j.bpobgyn.2015.08.010.

Lerou P. Embryonic stem cell derivation from human embryos. Methods Mol Biol. 2011;767: 31-35. https://doi.org/10.1007/978-1-61779-201-4_3.

Ilic D, Ogilvie C. Concise Review: Human Embryonic Stem Cells-What Have We Done? What Are We Doing? Where Are We Going? Stem Cells. 2017;35(1): 17-25. https://doi.org/10.1002/stem.2450.

Itskovitz-Eldor J. 20th Anniversary of Isolation of Human Embryonic Stem Cells: A Personal Perspective. Stem Cell Reports. 2018;10(5): 1439-1441. https://doi.org/10.1016/j.stemcr.2018.04.011.

Crook JM, Kravets L, Peura T, Firpo MT. Derivation of Human Embryonic Stem Cells. Methods Mol Biol. 2017;1590: 115-129. https://doi.org/10.1007/978-1-4939-6921-0_8.

Andrews PW. From teratocarcinomas to embryonic stem cells. Philos Trans R Soc Lond B Biol Sci. 2002;357(1420): 405-417. https://doi.org/10.1098/rstb.2002.1058.

Bonner AE, Wang Y, You M. Gene expression profiling of mouse teratocarcinomas uncovers epigenetic changes associated with the transformation of mouse embryonic stem cells. Neoplasia. 2004;6(5): 490-502. https://doi.org/10.1593/neo.04124.

Chambers I, Smith A. Self-renewal of teratocarcinoma and embryonic stem cells. Oncogene. 2004;23(43): 7150-7160. https://doi.org/10.1038/sj.onc.1207930.

Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells. 2006;24(3): 781-792. https://doi.org/10.1634/stemcells.2005-0330.

Weiss ML, Anderson C, Medicetty S, et al. Immune properties of human umbilical cord Wharton's jelly-derived cells. Stem Cells. 2008;26(11): 2865-2874. https://doi.org/10.1634/stemcells.2007-1028.

Weiss ML, Troyer DL. Stem cells in the umbilical cord. Stem Cell Rev. 2006;2(2): 155-162. https://doi.org/10.1007/s12015-006-0022-y.

Li T, Xia M, Gao Y, Chen Y, Xu Y. Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy. Expert Opin Biol Ther. 2015;15(9): 1293-1306. https://doi.org/10.1517/14712598.2015.1051528.

El Omar R, Beroud J, Stoltz JF, Menu P, Velot E, Decot V. Umbilical cord mesenchymal stem cells: the new gold standard for mesenchymal stem cell-based therapies? Tissue Eng Part B Rev. 2014;20(5): 523-544. https://doi.org/10.1089/ten.TEB.2013.0664.

Ding DC, Chang YH, Shyu WC, Lin SZ. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant. 2015;24(3): 339-347. https://doi.org/10.3727/096368915x686841.

Clevers H. STEM CELLS. What is an adult stem cell? Science. 2015;350(6266): 1319-1320. https://doi.org/10.1126/science.aad7016.

Prentice DA. Adult Stem Cells. Circ Res. 2019;124(6): 837-839. https://doi.org/10.1161/circresaha.118.313664.

Dulak J, Szade K, Szade A, Nowak W, Józkowicz A. Adult stem cells: hopes and hypes of regenerative medicine. Acta Biochim Pol. 2015;62(3): 329-337. https://doi.org/10.18388/abp.2015_1023.

Clevers H, Watt FM. Defining Adult Stem Cells by Function, not by Phenotype. Annu Rev Biochem. 2018;87: 1015-1027. https://doi.org/10.1146/annurev-biochem-062917-012341.

Crane GM, Jeffery E, Morrison SJ. Adult haematopoietic stem cell niches. Nat Rev Immunol. 2017;17(9): 573-590. https://doi.org/10.1038/nri.2017.53.

Gonçalves JT, Schafer ST, Gage FH. Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior. Cell. 2016;167(4): 897-914. https://doi.org/10.1016/j.cell.2016.10.021.

Kriegstein A, Alvarez-Buylla A. The glial nature of embryonic and adult neural stem cells. Annu Rev Neurosci. 2009;32: 149-184. https://doi.org/10.1146/annurev.neuro.051508.135600.

Zupanc GKH, Monaghan JR, Stocum DL. Adult Neural Stem Cells in Development, Regeneration, and Aging. Dev Neurobiol. 2019;79(5): 391-395. https://doi.org/10.1002/dneu.22702.

Sanberg PR, Eve DJ, Metcalf C, Borlongan CV. Advantages and challenges of alternative sources of adult-derived stem cells for brain repair in stroke. Prog Brain Res. 2012;201: 99-117. https://doi.org/10.1016/b978-0-444-59544-7.00006-8.

Macrin D, Joseph JP, Pillai AA, Devi A. Eminent Sources of Adult Mesenchymal Stem Cells and Their Therapeutic Imminence. Stem Cell Rev Rep. 2017;13(6): 741-756. https://doi.org/10.1007/s12015-017-9759-8.

Baker CL, Pera MF. Capturing Totipotent Stem Cells. Cell Stem Cell. 2018;22(1): 25-34. https://doi.org/10.1016/j.stem.2017.12.011.

Hayashi Y, Ohnuma K, Furue MK. Pluripotent Stem Cell Heterogeneity. Adv Exp Med Biol. 2019;1123: 71-94. https://doi.org/10.1007/978-3-030-11096-3_6.

Sobhani A, Khanlarkhani N, Baazm M, et al. Multipotent Stem Cell and Current Application. Acta Med Iran. 2017;55(1): 6-23.

Kempermann G, Song H, Gage FH. Neurogenesis in the Adult Hippocampus. Cold Spring Harb Perspect Biol. 2015;7(9): a018812. https://doi.org/10.1101/cshperspect.a018812.

Lim DA, Alvarez-Buylla A. The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis. Cold Spring Harb Perspect Biol. 2016;8(5). https://doi.org/10.1101/cshperspect.a018820.

McKay R. Stem cells in the central nervous system. Science. 1997;276(5309): 66-71. https://doi.org/10.1126/science.276.5309.66.

Daniela F, Vescovi AL, Bottai D. The stem cells as a potential treatment for neurodegeneration. Methods Mol Biol. 2007;399: 199-213. https://doi.org/10.1007/978-1-59745-504-6_14.

Ourednik V, Ourednik J, Park KI, Snyder EY. Neural stem cells -- a versatile tool for cell replacement and gene therapy in the central nervous system. Clin Genet. 1999;56(4): 267-278. https://doi.org/10.1034/j.1399-0004.1999.560403.x.

Zheng T, Marshall Ii GP, 2nd, Chen KA, Laywell ED. Transplantation of neural stem/progenitor cells into developing and adult CNS. Methods Mol Biol. 2009;482: 185-197. https://doi.org/10.1007/978-1-59745-060-7_12.

Dietrich J, Kempermann G. Role of endogenous neural stem cells in neurological disease and brain repair. Adv Exp Med Biol. 2006;557: 191-220. https://doi.org/10.1007/0-387-30128-3_12.

Sharp J, Keirstead HS. Stem cell-based cell replacement strategies for the central nervous system. Neurosci Lett. 2009;456(3): 107-111. https://doi.org/10.1016/j.neulet.2008.04.106.

Armstrong RJ, Svendsen CN. Neural stem cells: from cell biology to cell replacement. Cell Transplant. 2000;9(2): 139-152. https://doi.org/10.1177/096368970000900202.

Frisén J, Johansson CB, Lothian C, Lendahl U. Central nervous system stem cells in the embryo and adult. Cell Mol Life Sci. 1998;54(9): 935-945. https://doi.org/10.1007/s000180050224.

Trujillo CA, Schwindt TT, Martins AH, Alves JM, Mello LE, Ulrich H. Novel perspectives of neural stem cell differentiation: from neurotransmitters to therapeutics. Cytometry A. 2009;75(1): 38-53. https://doi.org/10.1002/cyto.a.20666.

Zhang J, Jiao J. Molecular Biomarkers for Embryonic and Adult Neural Stem Cell and Neurogenesis. Biomed Res Int. 2015;2015: 727542. https://doi.org/10.1155/2015/727542.

Yu J, Vodyanik MA, Smuga-Otto K, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318(5858): 1917-1920. https://doi.org/10.1126/science.1151526.

Takahashi K, Tanabe K, Ohnuki M, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 2007;131(5): 861-872. https://doi.org/10.1016/j.cell.2007.11.019.

Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126(4): 663-676. https://doi.org/10.1016/j.cell.2006.07.024.

Tobias AL, Thaci B, Auffinger B, et al. The timing of neural stem cell-based virotherapy is critical for optimal therapeutic efficacy when applied with radiation and chemotherapy for the treatment of glioblastoma. Stem Cells Transl Med. 2013;2(9): 655-666. https://doi.org/10.5966/sctm.2013-0039.

Ahmed AU, Thaci B, Tobias AL, et al. A preclinical evaluation of neural stem cell-based cell carrier for targeted antiglioma oncolytic virotherapy. J Natl Cancer Inst. 2013;105(13): 968-977. https://doi.org/10.1093/jnci/djt141.

Ahmed AU, Tyler MA, Thaci B, et al. A comparative study of neural and mesenchymal stem cell-based carriers for oncolytic adenovirus in a model of malignant glioma. Mol Pharm. 2011;8(5): 1559-1572. https://doi.org/10.1021/mp200161f.

Ahmed AU, Thaci B, Alexiades NG, et al. Neural stem cell-based cell carriers enhance therapeutic efficacy of an oncolytic adenovirus in an orthotopic mouse model of human glioblastoma. Mol Ther. 2011;19(9): 1714-1726. https://doi.org/10.1038/mt.2011.100.

Ulasov IV, Sonabend AM, Nandi S, Khramtsov A, Han Y, Lesniak MS. Combination of adenoviral virotherapy and temozolomide chemotherapy eradicates malignant glioma through autophagic and apoptotic cell death in vivo. Br J Cancer. 2009;100(7): 1154-1164. https://doi.org/10.1038/sj.bjc.6604969.

Nandi S, Ulasov IV, Tyler MA, et al. Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 2008;68(14): 5778-5784. https://doi.org/10.1158/0008-5472.Can-07-6441.

Ulasov IV, Zhu ZB, Tyler MA, et al. Survivin-driven and fiber-modified oncolytic adenovirus exhibits potent antitumor activity in established intracranial glioma. Hum Gene Ther. 2007;18(7): 589-602. https://doi.org/10.1089/hum.2007.002.

Mutukula N, Elkabetz Y. "Neural Killer" Cells: Autologous Cytotoxic Neural Stem Cells for Fighting Glioma. Cell Stem Cell. 2017;20(4): 426-428. https://doi.org/10.1016/j.stem.2017.03.019.

Bagó JR, Okolie O, Dumitru R, et al. Tumor-homing cytotoxic human induced neural stem cells for cancer therapy. Sci Transl Med. 2017;9(375). https://doi.org/10.1126/scitranslmed.aah6510.

Bagó JR, Sheets KT, Hingtgen SD. Neural stem cell therapy for cancer. Methods. 2016;99: 37-43. https://doi.org/10.1016/j.ymeth.2015.08.013.

Vieira de Castro J, Gomes ED, Granja S, et al. Impact of mesenchymal stem cells' secretome on glioblastoma pathophysiology. J Transl Med. 2017;15(1): 200. https://doi.org/10.1186/s12967-017-1303-8.

Gomes ED, Vieira de Castro J, Costa BM, Salgado AJ. The impact of Mesenchymal Stem Cells and their secretome as a treatment for gliomas. Biochimie. 2018;155: 59-66. https://doi.org/10.1016/j.biochi.2018.07.008.

Aboody KS, Brown A, Rainov NG, et al. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci U S A. 2000;97(23): 12846-12851. https://doi.org/10.1073/pnas.97.23.12846.

Brown AB, Yang W, Schmidt NO, et al. Intravascular delivery of neural stem cell lines to target intracranial and extracranial tumors of neural and non-neural origin. Hum Gene Ther. 2003;14(18): 1777-1785. https://doi.org/10.1089/104303403322611782.

Oh MC, Lim DA. Novel treatment strategies for malignant gliomas using neural stem cells. Neurotherapeutics. 2009;6(3): 458-464. https://doi.org/10.1016/j.nurt.2009.05.003.

Kim SK, Kim SU, Park IH, et al. Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression. Clin Cancer Res. 2006;12(18): 5550-5556. https://doi.org/10.1158/1078-0432.Ccr-05-2508.

Yang B, Wu X, Mao Y, et al. Dual-targeted antitumor effects against brainstem glioma by intravenous delivery of tumor necrosis factor-related, apoptosis-inducing, ligand-engineered human mesenchymal stem cells. Neurosurgery. 2009;65(3): 610-624; discussion 624. https://doi.org/10.1227/01.Neu.0000350227.61132.A7.

Du W, Seah I, Bougazzoul O, et al. Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas. Proc Natl Acad Sci U S A. 2017;114(30): E6157-e6165. https://doi.org/10.1073/pnas.1700363114.

Shah K, Hingtgen S, Kasmieh R, et al. Bimodal viral vectors and in vivo imaging reveal the fate of human neural stem cells in experimental glioma model. J Neurosci. 2008;28(17): 4406-4413. https://doi.org/10.1523/jneurosci.0296-08.2008.

Cheng CY, Shetty R, Sekhar LN. Microsurgical Resection of a Large Intraventricular Trigonal Tumor: 3-Dimensional Operative Video. Oper Neurosurg (Hagerstown). 2018;15(6): E92-E93. https://doi.org/10.1093/ons/opy068.

Palumbo P, Lombardi F, Siragusa G, et al. Involvement of NOS2 Activity on Human Glioma Cell Growth, Clonogenic Potential, and Neurosphere Generation. Int J Mol Sci. 2018;19(9). https://doi.org/10.3390/ijms19092801.

Bellantoni G, Guerrini F, Del Maestro M, Galzio R, Luzzi S. Simple schwannomatosis or an incomplete Coffin-Siris? Report of a particular case. eNeurologicalSci. 2019;14: 31-33. https://doi.org/10.1016/j.ensci.2018.11.021.

Tran PB, Banisadr G, Ren D, Chenn A, Miller RJ. Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain. J Comp Neurol. 2007;500(6): 1007-1033. https://doi.org/10.1002/cne.21229.

Tang Y, Shah K, Messerli SM, Snyder E, Breakefield X, Weissleder R. In vivo tracking of neural progenitor cell migration to glioblastomas. Hum Gene Ther. 2003;14(13): 1247-1254. https://doi.org/10.1089/104303403767740786.

Koizumi S, Gu C, Amano S, et al. Migration of mouse-induced pluripotent stem cells to glioma-conditioned medium is mediated by tumor-associated specific growth factors. Oncol Lett. 2011;2(2): 283-288. https://doi.org/10.3892/ol.2011.234.

Ricci A, Di Vitantonio H, De Paulis D, et al. Cortical aneurysms of the middle cerebral artery: A review of the literature. Surg Neurol Int. 2017;8: 117. https://doi.org/10.4103/sni.sni_50_17.

Luzzi S, Elia A, Del Maestro M, et al. Indication, Timing, and Surgical Treatment of Spontaneous Intracerebral Hemorrhage: Systematic Review and Proposal of a Management Algorithm. World Neurosurg. 2019. https://doi.org/10.1016/j.wneu.2019.01.016.

Schmidt NO, Koeder D, Messing M, et al. Vascular endothelial growth factor-stimulated cerebral microvascular endothelial cells mediate the recruitment of neural stem cells to the neurovascular niche. Brain Res. 2009;1268: 24-37. https://doi.org/10.1016/j.brainres.2009.02.065.

Lourenco S, Teixeira VH, Kalber T, Jose RJ, Floto RA, Janes SM. Macrophage migration inhibitory factor-CXCR4 is the dominant chemotactic axis in human mesenchymal stem cell recruitment to tumors. J Immunol. 2015;194(7): 3463-3474. https://doi.org/10.4049/jimmunol.1402097.

Yamazoe T, Koizumi S, Yamasaki T, Amano S, Tokuyama T, Namba H. Potent tumor tropism of induced pluripotent stem cells and induced pluripotent stem cell-derived neural stem cells in the mouse intracerebral glioma model. Int J Oncol. 2015;46(1): 147-152. https://doi.org/10.3892/ijo.2014.2702.

Stuckey DW, Shah K. Stem cell-based therapies for cancer treatment: separating hope from hype. Nat Rev Cancer. 2014;14(10): 683-691. https://doi.org/10.1038/nrc3798.

Millimaggi DF, Norcia VD, Luzzi S, Alfiero T, Galzio RJ, Ricci A. Minimally Invasive Transforaminal Lumbar Interbody Fusion with Percutaneous Bilateral Pedicle Screw Fixation for Lumbosacral Spine Degenerative Diseases. A Retrospective Database of 40 Consecutive Cases and Literature Review. Turk Neurosurg. 2018;28(3): 454-461. https://doi.org/10.5137/1019-5149.JTN.19479-16.0.

Rolfe A, Sun D. Stem Cell Therapy in Brain Trauma: Implications for Repair and Regeneration of Injured Brain in Experimental TBI Models. CRC Press/Taylor & Francis, Boca Raton (FL); 2015.

Zoia C, Bongetta D, Dorelli G, Luzzi S, Maestro MD, Galzio RJ. Transnasal endoscopic removal of a retrochiasmatic cavernoma: A case report and review of literature. Surg Neurol Int. 2019;10: 76. https://doi.org/10.25259/SNI-132-2019.

Shah K. Stem cell-based therapies for tumors in the brain: are we there yet? Neuro Oncol. 2016;18(8): 1066-1078. https://doi.org/10.1093/neuonc/now096.

Luzzi S, Del Maestro M, Elia A, et al. Morphometric and Radiomorphometric Study of the Correlation Between the Foramen Magnum Region and the Anterior and Posterolateral Approaches to Ventral Intradural Lesions. Turk Neurosurg. 2019. https://doi.org/10.5137/1019-5149.JTN.26052-19.2.

Luzzi S, Zoia C, Rampini AD, et al. Lateral Transorbital Neuroendoscopic Approach for Intraconal Meningioma of the Orbital Apex: Technical Nuances and Literature Review. World Neurosurg. 2019;131: 10-17. https://doi.org/10.1016/j.wneu.2019.07.152.