{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T20:14:29Z","timestamp":1778098469351,"version":"3.51.4"},"reference-count":90,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T00:00:00Z","timestamp":1522800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,4,4]],"date-time":"2018-04-04T00:00:00Z","timestamp":1522800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Regen Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The prospects for cell replacement in spinal cord diseases are impeded by inefficient stem cell delivery. The deep location of the spinal cord and complex surgical access, as well as densely packed vital structures, question the feasibility of the widespread use of multiple spinal cord punctures to inject stem cells. Disorders characterized by disseminated pathology are particularly appealing for the distribution of cells globally throughout the spinal cord in a minimally invasive fashion. The intrathecal space, with access to a relatively large surface area along the spinal cord, is an attractive route for global stem cell delivery, and, indeed, is highly promising, but the success of this approach relies on the ability of cells (1) to survive in the cerebrospinal fluid (CSF), (2) to adhere to the spinal cord surface, and (3) to migrate, ultimately, into the parenchyma. Intrathecal infusion of cell suspension, however, has been insufficient and we postulate that embedding transplanted cells within hydrogel scaffolds will facilitate reaching these goals. In this review, we focus on practical considerations that render the intrathecal approach clinically viable, and then discuss the characteristics of various biomaterials that are suitable to serve as scaffolds. We also propose strategies to modulate the local microenvironment with nanoparticle carriers to improve the functionality of cellular grafts. Finally, we provide an overview of imaging modalities for in vivo monitoring and characterization of biomaterials and stem cells. This comprehensive review should serve as a guide for those planning preclinical and clinical studies on intrathecal stem cell transplantation.<\/jats:p>","DOI":"10.1038\/s41536-018-0046-3","type":"journal-article","created":{"date-parts":[[2018,3,29]],"date-time":"2018-03-29T22:52:15Z","timestamp":1522363935000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Hydrogel-based scaffolds to support intrathecal stem cell transplantation as a gateway to the spinal cord: clinical needs, biomaterials, and imaging technologies"],"prefix":"10.1038","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7052-8837","authenticated-orcid":false,"given":"J. Miguel","family":"Oliveira","sequence":"first","affiliation":[]},{"given":"Luisa","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Joana","family":"Silva-Correia","sequence":"additional","affiliation":[]},{"given":"S\u00edlvia","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Malgorzata","family":"Majchrzak","sequence":"additional","affiliation":[]},{"given":"Barbara","family":"Lukomska","sequence":"additional","affiliation":[]},{"given":"Luiza","family":"Stanaszek","sequence":"additional","affiliation":[]},{"given":"Paulina","family":"Strymecka","sequence":"additional","affiliation":[]},{"given":"Izabela","family":"Malysz-Cymborska","sequence":"additional","affiliation":[]},{"given":"Dominika","family":"Golubczyk","sequence":"additional","affiliation":[]},{"given":"Lukasz","family":"Kalkowski","sequence":"additional","affiliation":[]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Miroslaw","family":"Janowski","sequence":"additional","affiliation":[]},{"given":"Piotr","family":"Walczak","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2018,4,4]]},"reference":[{"key":"46_CR1","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.stem.2008.03.020","volume":"2","author":"MS Windrem","year":"2008","unstructured":"Windrem, M. S. et al. Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell. 2, 553\u2013565 (2008).","journal-title":"Cell Stem Cell."},{"key":"46_CR2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.expneurol.2017.02.005","volume":"291","author":"A Lyczek","year":"2017","unstructured":"Lyczek, A. et al. Transplanted human glial-restricted progenitors can rescue the survival of dysmyelinated mice independent of the production of mature, compact myelin. Exp. Neurol. 291, 74\u201386 (2017).","journal-title":"Exp. Neurol."},{"key":"46_CR3","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1001\/jamaneurol.2013.4749","volume":"71","author":"Z Kefalopoulou","year":"2014","unstructured":"Kefalopoulou, Z. et al. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol. 71, 83\u201387 (2014).","journal-title":"JAMA Neurol."},{"key":"46_CR4","doi-asserted-by":"crossref","unstructured":"Steinberg, G. K., Kondziolka, D., Bates, D. & SB623 Stroke Phase 1\/2A Study Group. Response by Steinberg et al. to letter regarding article, \u201cClinical Outcomes of Transplanted Modified Bone Marrow-Derived Mesenchymal Stem Cells in Stroke: A Phase 1\/2A Study\u201d. Stroke 47, e269 (2016).","DOI":"10.1161\/STROKEAHA.116.015209"},{"key":"46_CR5","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/S1474-4422(17)30046-7","volume":"16","author":"DC Hess","year":"2017","unstructured":"Hess, D. C. et al. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 16, 360\u2013368 (2017).","journal-title":"Lancet Neurol."},{"key":"46_CR6","doi-asserted-by":"publisher","first-page":"2950","DOI":"10.1089\/neu.2016.4895","volume":"34","author":"KD Anderson","year":"2017","unstructured":"Anderson, K. D. et al. Safety of autologous human schwann cell transplantation in subacute thoracic spinal cord injury. J. Neurotrauma 34, 2950\u20132963 (2017).","journal-title":"J. Neurotrauma"},{"key":"46_CR7","doi-asserted-by":"publisher","first-page":"155ra137","DOI":"10.1126\/scitranslmed.3004373","volume":"4","author":"N Gupta","year":"2012","unstructured":"Gupta, N. et al. Neural stem cell engraftment and myelination in the human brain. Sci. Transl. Med. 4, 155ra137\u2013155ra137 (2012).","journal-title":"Sci. Transl. Med."},{"key":"46_CR8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097631","volume":"9","author":"M Janowski","year":"2014","unstructured":"Janowski, M. et al. Long-term MRI cell tracking after intraventricular delivery in a patient with global cerebral ischemia and prospects for magnetic navigation of stem cells within the CSF. PLoS ONE 9, e97631 (2014).","journal-title":"PLoS ONE"},{"key":"46_CR9","doi-asserted-by":"publisher","first-page":"2346","DOI":"10.1177\/0271678X16665853","volume":"37","author":"P Walczak","year":"2016","unstructured":"Walczak, P. et al. Real-time MRI for precise and predictable intra-arterial stem cell delivery to the central nervous system. J. Cereb. Blood Flow. Metab. 37, 2346\u20132358 (2016).","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"46_CR10","first-page":"258","volume":"43","author":"P Kunert","year":"2009","unstructured":"Kunert, P., Janowski, M., Zakrzewska, A. & Marchel, A. Syringoperitoneal shunt in the treatment of syringomyelia. Neurol. Neurochir. Pol. 43, 258\u2013262 (2009).","journal-title":"Neurol. Neurochir. Pol."},{"key":"46_CR11","doi-asserted-by":"publisher","first-page":"1937","DOI":"10.1007\/s00586-017-5067-x","volume":"26","author":"Z Zhao","year":"2017","unstructured":"Zhao, Z. et al. The effect from different numbers of segmental arteries ligation to the spinal cord in the clinical practice of posterior vertebral column resection correction. Eur. Spine J. 26, 1937\u20131944 (2017).","journal-title":"Eur. Spine J."},{"key":"46_CR12","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1038\/nn.2210","volume":"11","author":"AC Lepore","year":"2008","unstructured":"Lepore, A. C. et al. Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat. Neurosci. 11, 1294\u20131301 (2008).","journal-title":"Nat. Neurosci."},{"key":"46_CR13","doi-asserted-by":"publisher","first-page":"E164","DOI":"10.1097\/BRS.0b013e3181d77a47","volume":"36","author":"B Raore","year":"2011","unstructured":"Raore, B. et al. Cervical multilevel intraspinal stem cell therapy: assessment of surgical risks in Gottingen minipigs. Spine 36, E164\u2013E171 (2011).","journal-title":"Spine"},{"key":"46_CR14","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1227\/NEU.0000000000000882","volume":"77","author":"J Gutierrez","year":"2015","unstructured":"Gutierrez, J. et al. Preclinical validation of multilevel intraparenchymal stem cell therapy in the porcine spinal cord. Neurosurgery 77, 604\u2013612 (2015).","journal-title":"Neurosurgery"},{"key":"46_CR15","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1212\/WNL.0000000000002889","volume":"87","author":"JD Glass","year":"2016","unstructured":"Glass, J. D. et al. Transplantation of spinal cord-derived neural stem cells for ALS: analysis of phase 1 and 2 trials. Neurology 87, 392\u2013400 (2016).","journal-title":"Neurology"},{"key":"46_CR16","doi-asserted-by":"publisher","unstructured":"Levi, A. D. et al. Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Neurosurgery https:\/\/doi.org\/10.1093\/neuros\/nyx250 (2017).","DOI":"10.1093\/neuros\/nyx250"},{"key":"46_CR17","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1097\/00006123-199902000-00118","volume":"44","author":"JB Wahlig","year":"1999","unstructured":"Wahlig, J. B., Welch, W. C., Kang, J. D. & Jungreis, C. A. Cervical intrathecal catheter placement for cerebrospinal fluid drainage: technical case report. Neurosurgery 44, 419\u2013421 (1999).","journal-title":"Neurosurgery"},{"key":"46_CR18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.expneurol.2017.07.009","volume":"297","author":"M Kanemitsu","year":"2017","unstructured":"Kanemitsu, M. et al. EMMPRIN overexpression in SVZ neural progenitor cells increases their migration towards ischemic cortex. Exp. Neurol. 297, 14\u201324 (2017).","journal-title":"Exp. Neurol."},{"key":"46_CR19","doi-asserted-by":"publisher","first-page":"948040","DOI":"10.1155\/2015\/948040","volume":"2015","author":"RC Assuncao-Silva","year":"2015","unstructured":"Assuncao-Silva, R. C., Gomes, E. D., Sousa, N., Silva, N. A. & Salgado, A. J. Hydrogels and cell based therapies in spinal cord injury regeneration. Stem Cells Int. 2015, 948040 (2015).","journal-title":"Stem Cells Int."},{"key":"46_CR20","doi-asserted-by":"publisher","first-page":"045015","DOI":"10.1088\/1748-6041\/9\/4\/045015","volume":"9","author":"JB Shim","year":"2014","unstructured":"Shim, J. B., Ankeny, R. F., Kim, H., Nerem, R. M. & Khang, G. A study of a three-dimensional PLGA sponge containing natural polymers co-cultured with endothelial and mesenchymal stem cells as a tissue engineering scaffold. Biomed. Mater. 9, 045015 (2014).","journal-title":"Biomed. Mater."},{"key":"46_CR21","doi-asserted-by":"publisher","first-page":"3663","DOI":"10.1016\/j.biomaterials.2004.09.053","volume":"26","author":"J Tan","year":"2005","unstructured":"Tan, J., Gemeinhart, R. A., Ma, M. & Saltzman, W. M. Improved cell adhesion and proliferation on synthetic phosphonic acid-containing hydrogels. Biomaterials 26, 3663\u20133671 (2005).","journal-title":"Biomaterials"},{"key":"46_CR22","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.biomaterials.2005.07.008","volume":"27","author":"A Jain","year":"2006","unstructured":"Jain, A., Kim, Y. T., McKeon, R. J. & Bellamkonda, R. V. In situ gelling hydrogels for conformal repair of spinal cord defects, and local delivery of BDNF after spinal cord injury. Biomaterials 27, 497\u2013504 (2006).","journal-title":"Biomaterials"},{"key":"46_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biomaterials.2017.05.008","volume":"136","author":"MM Adil","year":"2017","unstructured":"Adil, M. M. et al. Engineered hydrogels increase the post-transplantation survival of encapsulated hESC-derived midbrain dopaminergic neurons. Biomaterials 136, 1\u201311 (2017).","journal-title":"Biomaterials"},{"key":"46_CR24","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.stemcr.2015.04.008","volume":"4","author":"BG Ballios","year":"2015","unstructured":"Ballios, B. G. et al. A hyaluronan-based injectable hydrogel improves the survival and integration of stem cell progeny following transplantation. Stem Cell. Rep. 4, 1031\u20131045 (2015).","journal-title":"Stem Cell. Rep."},{"key":"46_CR25","doi-asserted-by":"publisher","first-page":"024101","DOI":"10.1088\/1748-6041\/7\/2\/024101","volume":"7","author":"MM Pakulska","year":"2012","unstructured":"Pakulska, M. M., Ballios, B. G. & Shoichet, M. S. Injectable hydrogels for central nervous system therapy. Biomed. Mater. 7, 024101 (2012).","journal-title":"Biomed. Mater."},{"key":"46_CR26","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1089\/ten.teb.2014.0290","volume":"21","author":"LM Delgado","year":"2015","unstructured":"Delgado, L. M., Bayon, Y., Pandit, A. & Zeugolis, D. I. To cross-link or not to cross-link? Cross-linking associated foreign body response of collagen-based devices. Tissue Eng. Part B Rev. 21, 298\u2013313 (2015).","journal-title":"Tissue Eng. Part B Rev."},{"key":"46_CR27","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1016\/j.biomaterials.2004.07.018","volume":"26","author":"KS Masters","year":"2005","unstructured":"Masters, K. S., Shah, D. N., Leinwand, L. A. & Anseth, K. S. Crosslinked hyaluronan scaffolds as a biologically active carrier for valvular interstitial cells. Biomaterials 26, 2517\u20132525 (2005).","journal-title":"Biomaterials"},{"key":"46_CR28","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1016\/j.biomaterials.2005.11.015","volume":"27","author":"D Gupta","year":"2006","unstructured":"Gupta, D., Tator, C. H. & Shoichet, M. S. Fast-gelling injectable blend of hyaluronan and methylcellulose for intrathecal, localized delivery to the injured spinal cord. Biomaterials 27, 2370\u20132379 (2006).","journal-title":"Biomaterials"},{"key":"46_CR29","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1016\/j.biomaterials.2013.02.002","volume":"34","author":"AJ Mothe","year":"2013","unstructured":"Mothe, A. J., Tam, R. Y., Zahir, T., Tator, C. H. & Shoichet, M. S. Repair of the injured spinal cord by transplantation of neural stem cells in a hyaluronan-based hydrogel. Biomaterials 34, 3775\u20133783 (2013).","journal-title":"Biomaterials"},{"key":"46_CR30","doi-asserted-by":"publisher","first-page":"19402","DOI":"10.1039\/c2jm33680d","volume":"22","author":"RY Tam","year":"2012","unstructured":"Tam, R. Y., Cooke, M. J. & Shoichet, M. S. A covalently modified hydrogel blend of hyaluronan-methyl cellulose with peptides and growth factors influences neural stem\/progenitor cell fate. J. Mater. Chem. 22, 19402\u201319411 (2012).","journal-title":"J. Mater. Chem."},{"key":"46_CR31","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.biomaterials.2015.12.032","volume":"83","author":"T Fuhrmann","year":"2016","unstructured":"Fuhrmann, T. et al. Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model. Biomaterials 83, 23\u201336 (2016).","journal-title":"Biomaterials"},{"key":"46_CR32","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.biomaterials.2016.07.019","volume":"105","author":"ED Gomes","year":"2016","unstructured":"Gomes, E. D. et al. Combination of a peptide-modified gellan gum hydrogel with cell therapy in a lumbar spinal cord injury animal model. Biomaterials 105, 38\u201351 (2016).","journal-title":"Biomaterials"},{"key":"46_CR33","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1002\/jbm.a.34650","volume":"101","author":"J Silva-Correia","year":"2013","unstructured":"Silva-Correia, J. et al. Rheological and mechanical properties of acellular and cell-laden methacrylated gellan gum hydrogels. J. Biomed. Mater. Res. A. 101, 3438\u20133446 (2013).","journal-title":"J. Biomed. Mater. Res. A."},{"key":"46_CR34","doi-asserted-by":"publisher","first-page":"7630","DOI":"10.1016\/j.actbio.2013.04.030","volume":"9","author":"D Kesselman","year":"2013","unstructured":"Kesselman, D., Kossover, O., Mironi-Harpaz, I. & Seliktar, D. Time-dependent cellular morphogenesis and matrix stiffening in proteolytically responsive hydrogels. Acta Biomater. 9, 7630\u20137639 (2013).","journal-title":"Acta Biomater."},{"key":"46_CR35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.proeng.2013.05.116","volume":"59","author":"T Russo","year":"2013","unstructured":"Russo, T. et al. Systematic analysis of injectable materials and 3D rapid prototyped magnetic scaffolds: from CNS applications to soft and hard tissue repair\/regeneration. Procedia Eng. 59, 233\u2013239 (2013).","journal-title":"Procedia Eng."},{"key":"46_CR36","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.2147\/IJN.S61288","volume":"9","author":"CT Lu","year":"2014","unstructured":"Lu, C. T. et al. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int. J. Nanomed. 9, 2241\u20132257 (2014).","journal-title":"Int. J. Nanomed."},{"key":"46_CR37","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1080\/10611860701231810","volume":"15","author":"DF Emerich","year":"2007","unstructured":"Emerich, D. F. & Thanos, C. G. Targeted nanoparticle-based drug delivery and diagnosis. J. Drug. Target. 15, 163\u2013183 (2007).","journal-title":"J. Drug. Target."},{"key":"46_CR38","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1517\/14712598.8.8.1063","volume":"8","author":"AZ Wang","year":"2008","unstructured":"Wang, A. Z. et al. Biofunctionalized targeted nanoparticles for therapeutic applications. Expert. Opin. Biol. Ther. 8, 1063\u20131070 (2008).","journal-title":"Expert. Opin. Biol. Ther."},{"key":"46_CR39","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1016\/j.progpolymsci.2010.04.006","volume":"35","author":"JM Oliveira","year":"2010","unstructured":"Oliveira, J. M., Salgado, A. J., Sousa, N., Mano, J. F. & Reis, R. L. Dendrimers and derivatives as a potential therapeutic tool in regenerative medicine strategies\u2014a review. Prog. Polym. Sci. 35, 1163\u20131194 (2010).","journal-title":"Prog. Polym. Sci."},{"key":"46_CR40","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1016\/j.addr.2005.09.018","volume":"57","author":"S Svenson","year":"2005","unstructured":"Svenson, S. & Tomalia, D. A. Dendrimers in biomedical applications - reflections on the field. Adv. Drug Deliv. Rev. 57, 2106\u20132129 (2005).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"46_CR41","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.drudis.2010.01.009","volume":"15","author":"AR Menjoge","year":"2010","unstructured":"Menjoge, A. R., Kannan, R. M. & Tomalia, D. A. Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov. Today 15, 171\u2013185 (2010).","journal-title":"Drug Discov. Today"},{"key":"46_CR42","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1002\/adfm.200800165","volume":"18","author":"JM Oliveira","year":"2008","unstructured":"Oliveira, J. M. et al. Surface engineered carboxymethylchitosan\/poly(amidoamine) dendrimer nanoparticles for intracellular targeting. Adv. Funct. Mater. 18, 1840\u20131853 (2008).","journal-title":"Adv. Funct. Mater."},{"key":"46_CR43","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1002\/smll.201503492","volume":"12","author":"SR Cerqueira","year":"2016","unstructured":"Cerqueira, S. R. et al. Microglia response and in vivo therapeutic potential of methylprednisolone-loaded dendrimer nanoparticles in spinal cord injury. Small 12, 972\u2013972 (2016).","journal-title":"Small"},{"key":"46_CR44","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1016\/j.jmmm.2010.11.059","volume":"323","author":"C Alexiou","year":"2011","unstructured":"Alexiou, C. et al. Cancer therapy with drug loaded magnetic nanoparticles\u2014magnetic drug targeting. J Magn. Magn. Mater. 323, 1404\u20131407 (2011).","journal-title":"J Magn. Magn. Mater."},{"key":"46_CR45","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.nano.2011.05.016","volume":"8","author":"S Parveen","year":"2012","unstructured":"Parveen, S., Misra, R. & Sahoo, S. K. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomedicine 8, 147\u2013166 (2012).","journal-title":"Nanomedicine"},{"key":"46_CR46","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.2217\/nnm.13.69","volume":"9","author":"E Lueshen","year":"2014","unstructured":"Lueshen, E. et al. Intrathecal magnetic drug targeting using gold-coated magnetite nanoparticles in a human spine model. Nanomed 9, 1155\u20131169 (2014).","journal-title":"Nanomed"},{"key":"46_CR47","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1166\/jbn.2015.1907","volume":"11","author":"E Lueshen","year":"2015","unstructured":"Lueshen, E., Venugopal, I., Soni, T., Alaraj, A. & Linninger, A. Implant-assisted intrathecal magnetic drug targeting to aid in therapeutic nanoparticle localization for potential treatment of central nervous system disorders. J. Biomed. Nanotechnol. 11, 253\u2013261 (2015).","journal-title":"J. Biomed. Nanotechnol."},{"key":"46_CR48","doi-asserted-by":"publisher","first-page":"865","DOI":"10.2217\/nnm-2016-0418","volume":"12","author":"I Venugopal","year":"2017","unstructured":"Venugopal, I., Habib, N. & Linninger, A. Intrathecal magnetic drug targeting for localized delivery of therapeutics in the CNS. Nanomed 12, 865\u2013877 (2017).","journal-title":"Nanomed"},{"key":"46_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.colsurfb.2009.09.001","volume":"75","author":"A Kumari","year":"2010","unstructured":"Kumari, A., Yadav, S. K. & Yadav, S. C. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf. B Biointerfaces 75, 1\u201318 (2010).","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"46_CR50","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.ijpharm.2016.01.011","volume":"499","author":"AD Holmkvist","year":"2016","unstructured":"Holmkvist, A. D., Friberg, A., Nilsson, U. J. & Schouenborg, J. Hydrophobic ion pairing of a minocycline\/Ca(2+)\/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release. Int. J. Pharm. 499, 351\u2013357 (2016).","journal-title":"Int. J. Pharm."},{"key":"46_CR51","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1007\/s00259-010-1695-7","volume":"38","author":"G Lucignani","year":"2011","unstructured":"Lucignani, G. & Rodriguez-Porcel, M. In vivo imaging for stem cell therapy: new developments and future challenges. Eur. J. Nucl. Med. Mol. Imaging 38, 400\u2013405, (2011).","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"46_CR52","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1089\/scd.2009.0271","volume":"19","author":"M Janowski","year":"2010","unstructured":"Janowski, M., Walczak, P. & Date, I. Intravenous route of cell delivery for treatment of neurological disorders: a meta-analysis of preclinical results. Stem. Cells. Dev. 19, 5\u201316 (2010).","journal-title":"Stem. Cells. Dev."},{"key":"46_CR53","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/glia.21119","volume":"59","author":"P Walczak","year":"2011","unstructured":"Walczak, P. et al. Human glial-restricted progenitors survive, proliferate, and preserve electrophysiological function in rats with focal inflammatory spinal cord demyelination. Glia 59, 499\u2013510 (2011).","journal-title":"Glia"},{"key":"46_CR54","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1016\/j.addr.2012.07.008","volume":"64","author":"M Janowski","year":"2012","unstructured":"Janowski, M., Bulte, J. W. & Walczak, P. Personalized nanomedicine advancements for stem cell tracking. Adv. Drug. Deliv. Rev. 64, 1488\u20131507 (2012).","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"46_CR55","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.copbio.2009.01.009","volume":"20","author":"JC Rasmussen","year":"2009","unstructured":"Rasmussen, J. C., Tan, I. C., Marshall, M. V., Fife, C. E. & Sevick-Muraca, E. M. Lymphatic imaging in humans with near-infrared fluorescence. Curr. Opin. Biotechnol. 20, 74\u201382 (2009).","journal-title":"Curr. Opin. Biotechnol."},{"key":"46_CR56","doi-asserted-by":"publisher","first-page":"1600478","DOI":"10.1002\/mabi.201600478","volume":"17","author":"AR Short","year":"2017","unstructured":"Short, A. R. et al. Imaging cell-matrix interactions in 3D collagen hydrogel culture systems. Macromol. Biosci. 17, 1600478 (2017).","journal-title":"Macromol. Biosci."},{"key":"46_CR57","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1038\/nmat3525","volume":"12","author":"KW Chan","year":"2013","unstructured":"Chan, K. W. et al. MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Nat. Mater. 12, 268\u2013275 (2013).","journal-title":"Nat. Mater."},{"key":"46_CR58","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jconrel.2014.02.005","volume":"180","author":"KW Chan","year":"2014","unstructured":"Chan, K. W. et al. A diaCEST MRI approach for monitoring liposomal accumulation in tumors. J. Control Release 180, 51\u201359 (2014).","journal-title":"J. Control Release"},{"key":"46_CR59","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.1002\/anie.201007494","volume":"50","author":"J Kim","year":"2011","unstructured":"Kim, J. et al. Multifunctional capsule-in-capsules for immunoprotection and trimodal imaging. Angew. Chem. 50, 2317\u20132321 (2011).","journal-title":"Angew. Chem."},{"key":"46_CR60","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3171\/2016.8.SPINE16263","volume":"26","author":"S Robinson","year":"2017","unstructured":"Robinson, S. et al. Image-guided intrathecal baclofen pump catheter implantation: a technical note and case series. J. Neurosurg. Spine 26, 621\u2013627 (2017).","journal-title":"J. Neurosurg. Spine"},{"key":"46_CR61","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1089\/ten.tec.2010.0150","volume":"16","author":"EM Brey","year":"2010","unstructured":"Brey, E. M. et al. X-ray imaging of poly(ethylene glycol) hydrogels without contrast agents. Tissue Eng. Part C Methods 16, 1597\u20131600 (2010).","journal-title":"Tissue Eng. Part C Methods"},{"key":"46_CR62","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1089\/ten.tec.2008.0436","volume":"15","author":"KA Faraj","year":"2009","unstructured":"Faraj, K. A. et al. Micro-computed tomographical imaging of soft biological materials using contrast techniques. Tissue Eng. Part C Methods 15, 493\u2013499 (2009).","journal-title":"Tissue Eng. Part C Methods"},{"key":"46_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-017-3076-0","volume":"17","author":"H Poort","year":"2017","unstructured":"Poort, H. et al. Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer. BMC Cancer 17, 81 (2017).","journal-title":"BMC Cancer"},{"key":"46_CR64","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0169656","volume":"12","author":"H Qin","year":"2017","unstructured":"Qin, H. et al. Rabbit model of human gliomas: implications for intra-arterial drug delivery. PLoS ONE 12, e0169656 (2017).","journal-title":"PLoS ONE"},{"key":"46_CR65","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074658","volume":"8","author":"M Barczewska","year":"2013","unstructured":"Barczewska, M. et al. MR monitoring of minimally invasive delivery of mesenchymal stem cells into the porcine intervertebral disc. PLoS. One. 8, e74658 (2013).","journal-title":"PLoS. One."},{"key":"46_CR66","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/nm1581","volume":"13","author":"BP Barnett","year":"2007","unstructured":"Barnett, B. P. et al. Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells. Nat. Med. 13, 986\u2013991 (2007).","journal-title":"Nat. Med."},{"key":"46_CR67","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.biomaterials.2014.11.050","volume":"42","author":"Y Liang","year":"2015","unstructured":"Liang, Y. et al. Label-free imaging of gelatin-containing hydrogel scaffolds. Biomaterials 42, 144\u2013150 (2015).","journal-title":"Biomaterials"},{"key":"46_CR68","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/wnan.140","volume":"3","author":"SM Cromer Berman","year":"2011","unstructured":"Cromer Berman, S. M., Walczak, P. & Bulte, J. W. Tracking stem cells using magnetic nanoparticles. Wiley interdisciplinary reviews. Nanomed. Nanobiotechnol. 3, 343\u2013355 (2011).","journal-title":"Nanomed. Nanobiotechnol."},{"key":"46_CR69","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.biomaterials.2015.11.021","volume":"77","author":"FJ Nicholls","year":"2016","unstructured":"Nicholls, F. J. et al. DNA-gadolinium-gold nanoparticles for in vivo T1 MR imaging of transplanted human neural stem cells. Biomaterials 77, 291\u2013306 (2016).","journal-title":"Biomaterials"},{"key":"46_CR70","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/7651_2013_16","volume":"1052","author":"H Nejadnik","year":"2013","unstructured":"Nejadnik, H., Castillo, R. & Daldrup-Link, H. E. Magnetic resonance imaging and tracking of stem cells. Methods Mol. Biol. 1052, 167\u2013176 (2013).","journal-title":"Methods Mol. Biol."},{"key":"46_CR71","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1002\/wnan.35","volume":"1","author":"JM Janjic","year":"2009","unstructured":"Janjic, J. M. & Ahrens, E. T. Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 1, 492\u2013501 (2009).","journal-title":"Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol."},{"key":"46_CR72","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.biomaterials.2015.01.065","volume":"51","author":"A Leder","year":"2015","unstructured":"Leder, A. et al. Micron-sized iron oxide-containing particles for microRNA-targeted manipulation and MRI-based tracking of transplanted cells. Biomaterials 51, 129\u2013137 (2015).","journal-title":"Biomaterials"},{"key":"46_CR73","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1016\/j.biomaterials.2010.01.010","volume":"31","author":"J Xie","year":"2010","unstructured":"Xie, J. et al. PET\/NIRF\/MRI triple functional iron oxide nanoparticles. Biomaterials 31, 3016\u20133022 (2010).","journal-title":"Biomaterials"},{"key":"46_CR74","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1002\/mrm.22290","volume":"63","author":"DA Kedziorek","year":"2010","unstructured":"Kedziorek, D. A. et al. Gene expression profiling reveals early cellular responses to intracellular magnetic labeling with superparamagnetic iron oxide nanoparticles. Magn. Reson. Med. 63, 1031\u20131043 (2010).","journal-title":"Magn. Reson. Med."},{"key":"46_CR75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032326","volume":"7","author":"P Bigini","year":"2012","unstructured":"Bigini, P. et al. Longitudinal tracking of human fetal cells labeled with super paramagnetic iron oxide nanoparticles in the brain of mice with motor neuron disease. PLoS ONE 7, e32326 (2012).","journal-title":"PLoS ONE"},{"key":"46_CR76","first-page":"5543","volume":"10","author":"A Andrzejewska","year":"2015","unstructured":"Andrzejewska, A. et al. Pre- and postmortem imaging of transplanted cells. Int. J. Nanomed. 10, 5543\u20135559 (2015).","journal-title":"Int. J. Nanomed."},{"key":"46_CR77","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.1016\/j.transproceed.2008.05.084","volume":"40","author":"M Rigol","year":"2008","unstructured":"Rigol, M. et al. Hemosiderin deposits confounds tracking of iron-oxide-labeled stem cells: an experimental study. Transplant. Proc. 40, 3619\u20133622 (2008).","journal-title":"Transplant. Proc."},{"key":"46_CR78","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1007\/s10439-015-1482-5","volume":"44","author":"AA Appel","year":"2016","unstructured":"Appel, A. A. et al. X-ray phase contrast allows three dimensional, quantitative imaging of hydrogel implants. Ann. Biomed. Eng. 44, 773\u2013781 (2016).","journal-title":"Ann. Biomed. Eng."},{"key":"46_CR79","doi-asserted-by":"crossref","first-page":"188","DOI":"10.55782\/ane-2014-1984","volume":"74","author":"G Mohandas","year":"2014","unstructured":"Mohandas, G., Oskolkov, N., McMahon, M. T., Walczak, P. & Janowski, M. Porous tantalum and tantalum oxide nanoparticles for regenerative medicine. Acta Neurobiol. Exp. 74, 188\u2013196 (2014).","journal-title":"Acta Neurobiol. Exp."},{"key":"46_CR80","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.carbpol.2014.03.070","volume":"110","author":"X Yang","year":"2014","unstructured":"Yang, X. et al. Injectable hyaluronic acid hydrogel for 19F magnetic resonance imaging. Carbohydr. Polym. 110, 95\u201399 (2014).","journal-title":"Carbohydr. Polym."},{"key":"46_CR81","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1016\/j.biomaterials.2011.11.083","volume":"33","author":"JI Kim","year":"2012","unstructured":"Kim, J. I. et al. Long-term theranostic hydrogel system for solid tumors. Biomaterials 33, 2251\u20132259 (2012).","journal-title":"Biomaterials"},{"key":"46_CR82","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1002\/mabi.201400117","volume":"14","author":"Y Zhang","year":"2014","unstructured":"Zhang, Y. et al. Injectable in situ forming hybrid iron oxide-hyaluronic acid hydrogel for magnetic resonance imaging and drug delivery. Macromol. Biosci. 14, 1249\u20131259 (2014).","journal-title":"Macromol. Biosci."},{"key":"46_CR83","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1162\/153535003322750664","volume":"2","author":"BA Moffat","year":"2003","unstructured":"Moffat, B. A. et al. A novel polyacrylamide magnetic nanoparticle contrast agent for molecular imaging using MRI. Mol. Imaging 2, 324\u2013332 (2003).","journal-title":"Mol. Imaging"},{"key":"46_CR84","doi-asserted-by":"publisher","first-page":"2858","DOI":"10.1016\/j.biomaterials.2011.12.033","volume":"33","author":"E Bible","year":"2012","unstructured":"Bible, E. et al. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI. Biomaterials 33, 2858\u20132871 (2012).","journal-title":"Biomaterials"},{"key":"46_CR85","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jmr.2012.11.024","volume":"229","author":"E Vinogradov","year":"2013","unstructured":"Vinogradov, E., Sherry, A. D. & Lenkinski, R. E. CEST: from basic principles to applications, challenges and opportunities. J. Magn. Reson. 229, 155\u2013172 (2013).","journal-title":"J. Magn. Reson."},{"key":"46_CR86","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.biomaterials.2016.10.043","volume":"113","author":"T Jin","year":"2017","unstructured":"Jin, T. et al. Diamagnetic chemical exchange saturation transfer (diaCEST) affords magnetic resonance imaging of extracellular matrix hydrogel implantation in a rat model of stroke. Biomaterials 113, 176\u2013190 (2017).","journal-title":"Biomaterials"},{"key":"46_CR87","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1089\/ten.tec.2013.0587","volume":"20","author":"AB Allen","year":"2014","unstructured":"Allen, A. B., Gazit, Z., Su, S., Stevens, H. Y. & Guldberg, R. E. In vivo bioluminescent tracking of mesenchymal stem cells within large hydrogel constructs. Tissue Eng. Part C Methods 20, 806\u2013816 (2014).","journal-title":"Tissue Eng. Part C Methods"},{"key":"46_CR88","doi-asserted-by":"publisher","first-page":"5521","DOI":"10.1016\/j.biomaterials.2013.03.095","volume":"34","author":"Y Liang","year":"2013","unstructured":"Liang, Y., Walczak, P. & Bulte, J. W. The survival of engrafted neural stem cells within hyaluronic acid hydrogels. Biomaterials 34, 5521\u20135529 (2013).","journal-title":"Biomaterials"},{"key":"46_CR89","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000367","volume":"2","author":"RD Levit","year":"2013","unstructured":"Levit, R. D. et al. Cellular encapsulation enhances cardiac repair. J. Am. Heart Assoc. 2, e000367 (2013).","journal-title":"J. Am. Heart Assoc."},{"key":"46_CR90","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1007\/s00380-012-0275-0","volume":"28","author":"JJ Yang","year":"2013","unstructured":"Yang, J. J. et al. Real-time tracking of adipose tissue-derived stem cells with injectable scaffolds in the infarcted heart. Heart Vessel. 28, 385\u2013396 (2013).","journal-title":"Heart Vessel."}],"container-title":["npj Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41536-018-0046-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41536-018-0046-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41536-018-0046-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T12:40:32Z","timestamp":1719924032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41536-018-0046-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,4]]},"references-count":90,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["46"],"URL":"https:\/\/doi.org\/10.1038\/s41536-018-0046-3","relation":{},"ISSN":["2057-3995"],"issn-type":[{"value":"2057-3995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,4]]},"assertion":[{"value":"6 October 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2018","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2018","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 April 2018","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"8"}}