{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:26:41Z","timestamp":1761060401477,"version":"3.37.3"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"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":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mesenchymal stromal cells (MSCs) represent a key component of bone marrow (BM) microenvironment and display immune-regulatory properties. We performed a detailed analysis of biological\/functional properties of BM-MSCs derived from 33 pediatric patients affected by primary immune-deficiencies (PID-MSCs): 7 Chronic Granulomatous Disease (CGD), 15 Wiskott-Aldrich Syndrome (WAS), 11 Severe Combined Immunodeficiency (SCID). Results were compared with MSCs from 15 age-matched pediatric healthy-donors (HD-MSCs). Clonogenic and proliferative capacity, differentiation ability, immunophenotype, immunomodulatory properties were analyzed. WB and RT-qPCR for CYBB, WAS and ADA genes were performed. All PID-MSCs displayed clonogenic and proliferative capacity, morphology and immunophenotype comparable with HD-MSCs. PID-MSCs maintained the inhibitory effect on T- and B-lymphocyte proliferation, except for decreased inhibitory ability of SCID-MSCs at MSC:PBMC ratio 1:10. While HD- and CGD-MSCs were able to inhibit monocyte maturation into immature dendritic cells, in SCID- and WAS-MSCs this ability was reduced. After Toll-like Receptor priming, PID-MSCs displayed <jats:italic>in vitro<\/jats:italic> an altered gene expression profile of pro- and anti-inflammatory soluble factors. PID-MSCs displayed lower PPAR\u03b3 levels and WAS- and SCID-MSCs higher levels of key osteogenic markers, as compared with HD-MSCs. Our results indicate that PID-MSCs may be defective in some functional abilities; whether these defects contribute to disease pathophysiology deserves further investigation.<\/jats:p>","DOI":"10.1038\/s41598-017-08550-5","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T09:04:37Z","timestamp":1502269477000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Biological and functional characterization of bone marrow-derived mesenchymal stromal cells from patients affected by primary immunodeficiency"],"prefix":"10.1038","volume":"7","author":[{"given":"Nadia","family":"Starc","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Ingo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Conforti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Rossella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luigi","family":"Tomao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Pitisci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"De Mattia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Immacolata","family":"Brigida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Algeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Montanari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Palumbo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Merli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paolo","family":"Rossi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5398-1717","authenticated-orcid":false,"given":"Alessandro","family":"Aiuti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Locatelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Ester","family":"Bernardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,15]]},"reference":[{"key":"8550_CR1","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1182\/blood.V98.8.2396","volume":"98","author":"C Campagnoli","year":"2001","unstructured":"Campagnoli, C. et al. Identification of mesenchymal stem\/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood \n                           98, 2396\u20132402 (2001).","journal-title":"Blood"},{"key":"8550_CR2","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1634\/stemcells.2005-0342","volume":"24","author":"S Kern","year":"2006","unstructured":"Kern, S., Eichler, H., Stoeve, J., Kl\u00fcter, H. & Bieback, K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells \n                           24, 1294\u20131301 (2006).","journal-title":"Stem Cells"},{"key":"8550_CR3","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1126\/science.284.5411.143","volume":"284","author":"MF Pittenger","year":"1999","unstructured":"Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science \n                           284, 143\u2013147 (1999).","journal-title":"Science"},{"key":"8550_CR4","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1182\/blood-2007-10-119370","volume":"112","author":"H Karlsson","year":"2008","unstructured":"Karlsson, H. et al. Mesenchymal stem cells exert different effects on alloantigen and virus-specific T-cell responses. Blood \n                           112, 532\u2013541 (2008).","journal-title":"Blood"},{"key":"8550_CR5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1046\/j.1365-3083.2003.01176.x","volume":"57","author":"K Le Blanc","year":"2003","unstructured":"Le Blanc, K., Tammik, L., Sundberg, B., Haynesworth, S. E. & Ringd\u00e9n, O. Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses indipendently of the major histocompatibility complex. Scand J Immunol \n                           57, 11\u201320 (2003).","journal-title":"Scand J Immunol"},{"key":"8550_CR6","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1002\/art.27560","volume":"62","author":"F Schena","year":"2010","unstructured":"Schena, F. et al. Interferon-gamma-dependent inhibition of B cell activation by bone marrow-derived mesenchymal stem cells in a murine model of systemic lupus erythematosus. Arthritis Rheum \n                           62, 2776\u20132786 (2010).","journal-title":"Arthritis Rheum"},{"key":"8550_CR7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/icb.2012.62","volume":"91","author":"GM Spaggiari","year":"2013","unstructured":"Spaggiari, G. M. & Moretta, L. Cellular and molecular interactions of mesenchymal stem cells in innate immunity. Immunol Cell Biol. \n                           91, 27\u201331 (2013).","journal-title":"Immunol Cell Biol."},{"key":"8550_CR8","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1016\/S0140-6736(08)60690-X","volume":"10","author":"K Le Blanc","year":"2008","unstructured":"Le Blanc, K. et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet \n                           10, 1579\u20131586 (2008).","journal-title":"Lancet"},{"key":"8550_CR9","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1097\/TP.0b013e31821aba18","volume":"91","author":"KH Wu","year":"2011","unstructured":"Wu, K. H. et al. Effective treatment of severe steroid-resistant acute graft-versus-host disease with umbilical cord-derived mesenchymal stem cells. Transplantation \n                           91, 1412\u20131416 (2011).","journal-title":"Transplantation"},{"key":"8550_CR10","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1200\/JCO.2000.18.2.307","volume":"18","author":"ON Koc","year":"2000","unstructured":"Koc, O. N. et al. Rapid hematopoietic recovery after co-infusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol \n                           18, 307\u2013316 (2000).","journal-title":"J Clin Oncol"},{"key":"8550_CR11","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1182\/blood-2007-04-087056","volume":"110","author":"LM Ball","year":"2007","unstructured":"Ball, L. M. et al. Cotransplantation of ex vivo expanded mesenchymal stem cells accelerates lymphocyte recovery and may reduce the risk of graft failure in haploidentical hematopoietic stem cell transplantation. Blood \n                           110, 2764\u20132767 (2007).","journal-title":"Blood"},{"key":"8550_CR12","doi-asserted-by":"publisher","first-page":"561","DOI":"10.2174\/1567201810999131125222440","volume":"11","author":"K English","year":"2014","unstructured":"English, K., Mahon, B. P. & Wood, K. J. Mesenchymal stromal cells; role in tissue repair, drug discovery and immune modulation. Curr Drug Deliv \n                           11, 561\u2013571 (2014).","journal-title":"Curr Drug Deliv"},{"key":"8550_CR13","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1136\/gut.2010.214841","volume":"60","author":"R Ciccocioppo","year":"2011","unstructured":"Ciccocioppo, R. et al. Autologous bone marrow-derived mesenchymal stromal cells in the treatment of fistulising Crohn\u2019s disease. Gut \n                           60, 788\u2013798 (2011).","journal-title":"Gut"},{"issue":"17","key":"8550_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0819-7","volume":"3","author":"A Cras","year":"2015","unstructured":"Cras, A. et al. Update on mesenchymal stem cell-based therapy in lupus and scleroderma. Arthritis Res Ther \n                           3(17), 301, doi:10.1186\/s13075-015-0819-7 (2015).","journal-title":"Arthritis Res Ther"},{"key":"8550_CR15","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1007\/s10875-015-0201-1","volume":"35","author":"C Picard","year":"2015","unstructured":"Picard, C. et al. Primary Immunodeficiency Diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol \n                           35, 696\u2013726 (2015).","journal-title":"J Clin Immunol"},{"key":"8550_CR16","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/ng0495-414","volume":"9","author":"A Villa","year":"1995","unstructured":"Villa, A. et al. X-linked thrombocytopenia and Wiskott-Aldrich syndrome are allelic diseases with mutations in the WASP gene. Nat Genet \n                           9, 414\u2013417 (1995).","journal-title":"Nat Genet"},{"key":"8550_CR17","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/nyas.12049","volume":"1285","author":"MJ Massaad","year":"2013","unstructured":"Massaad, M. J., Ramesh, N. & Geha, R. S. Wiskott-Aldrich syndrome: a comprehensive review. Ann N Y Acad Sci \n                           1285, 26\u201343 (2013).","journal-title":"Ann N Y Acad Sci"},{"key":"8550_CR18","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1016\/j.molimm.2009.03.016","volume":"46","author":"G Di Matteo","year":"2009","unstructured":"Di Matteo, G. et al. Molecular characterization of a large cohort of patients with chronic granulomatous disease and identification of novel CYBB mutations: an Italian multicenter study. Mol Immunol \n                           46, 1935\u20131941 (2009).","journal-title":"Mol Immunol"},{"key":"8550_CR19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/bmb\/ldw009","volume":"118","author":"D Roos","year":"2016","unstructured":"Roos, D. Chronic granulomatous disease. Br Med Bull \n                           118, 50\u201363 (2016).","journal-title":"Br Med Bull"},{"key":"8550_CR20","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.iac.2015.07.002","volume":"35","author":"IK Chinn","year":"2015","unstructured":"Chinn, I. K. & Shearer, W. T. Severe Combined Immunodeficiency Disorders. Immunol Allergy Clin North Am \n                           35, 671\u2013694 (2015).","journal-title":"Immunol Allergy Clin North Am"},{"key":"8550_CR21","doi-asserted-by":"publisher","first-page":"3524","DOI":"10.1182\/blood-2009-06-189209","volume":"114","author":"HB Gaspar","year":"2009","unstructured":"Gaspar, H. B. et al. How I treat ADA deficiency. Blood \n                           114, 3524\u20133532 (2009).","journal-title":"Blood"},{"key":"8550_CR22","doi-asserted-by":"publisher","first-page":"2949","DOI":"10.1182\/blood-2011-06-363572","volume":"119","author":"JF Fernandes","year":"2002","unstructured":"Fernandes, J. F. et al. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood \n                           119, 2949\u20132955 (2002).","journal-title":"Blood"},{"key":"8550_CR23","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1182\/blood-2014-03-563817","volume":"124","author":"A Bertaina","year":"2014","unstructured":"Bertaina, A. et al. HLA-haploidentical stem cell transplantation after removal of \u03b1\u03b2+ T and B cells in children with nonmalignant disorders. Blood \n                           124, 822\u2013826 (2014).","journal-title":"Blood"},{"key":"8550_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1182\/blood-2016-01-688226","volume":"128","author":"MP Cicalese","year":"2016","unstructured":"Cicalese, M. P. et al. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood \n                           128, 45\u201354 (2016).","journal-title":"Blood"},{"key":"8550_CR25","doi-asserted-by":"publisher","DOI":"10.1126\/science.1233151","volume":"341","author":"A Aiuti","year":"2013","unstructured":"Aiuti, A. et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science \n                           341, 1233151 (2013).","journal-title":"Science"},{"key":"8550_CR26","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1080\/14653240600855905","volume":"8","author":"M Dominici","year":"2006","unstructured":"Dominici, M. et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy \n                           8, 315\u2013317 (2006).","journal-title":"Cytotherapy"},{"key":"8550_CR27","first-page":"845","volume":"88","author":"PS in\u2019t Anker","year":"2003","unstructured":"in\u2019t Anker, P. S. et al. Mesenchymal stem cells in human second-trimester bone marrow, liver, lung and spleen exhibit a similar immunophenotype but a heterogeneous multilineage differentiation potential. Haematologica \n                           88, 845\u2013852 (2003).","journal-title":"Haematologica"},{"key":"8550_CR28","doi-asserted-by":"publisher","first-page":"3838","DOI":"10.1182\/blood.V99.10.3838","volume":"99","author":"M Di Nicola","year":"2002","unstructured":"Di Nicola, M. et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or non specific mitogenic stimuli. Blood \n                           99, 3838\u20133843 (2002).","journal-title":"Blood"},{"key":"8550_CR29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076989","volume":"8","author":"A Conforti","year":"2013","unstructured":"Conforti, A. et al. Biological, functional and genetic characterization of bone marrow-derived mesenchymal stromal cells from pediatric patients affected by acute lymphoblastic leukemia. PLoS One \n                           8, e76989 (2013).","journal-title":"PLoS One"},{"issue":"1","key":"8550_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-017-0499-0","volume":"8","author":"WX Gao","year":"2017","unstructured":"Gao, W. X. et al. Effects of mesenchymal stem cells from human induced pluripotent stem cells on differentiation, maturation, and function of dendritic cells. Stem Cell Res Ther \n                           8(1), 48, doi:10.1186\/s13287-017-0499-0 (2017).","journal-title":"Stem Cell Res Ther"},{"key":"8550_CR31","doi-asserted-by":"publisher","first-page":"6576","DOI":"10.1182\/blood-2009-02-203943","volume":"113","author":"GM Spaggiari","year":"2009","unstructured":"Spaggiari, G. M., Abdelrazik, H., Becchetti, F. & Moretta, L. MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood \n                           113, 6576\u20136583 (2009).","journal-title":"Blood"},{"key":"8550_CR32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0010088","volume":"5","author":"RS Waterman","year":"2010","unstructured":"Waterman, R. S., Tomchuck, S. L., Henkle, S. L. & Betancourt, A. M. A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One \n                           5, e10088 (2010).","journal-title":"PLoS One"},{"key":"8550_CR33","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.bbrc.2015.07.002","volume":"464","author":"Y Lu","year":"2015","unstructured":"Lu, Y. et al. TLR4 plays a crucial role in MSC-induced inhibition of NK cell function. Biochem Biophys Res Commun \n                           464, 541\u2013547 (2015).","journal-title":"Biochem Biophys Res Commun"},{"key":"8550_CR34","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1038\/mt.2014.87","volume":"22","author":"M Chiriaco","year":"2014","unstructured":"Chiriaco, M. et al. Dual-regulated lentiviral vector for gene therapy of X-linked chronic granulomatosis. Mol Ther \n                           22, 1472\u201383 (2014).","journal-title":"Mol Ther"},{"key":"8550_CR35","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/sj.gt.3302863","volume":"14","author":"S Charrier","year":"2007","unstructured":"Charrier, S. et al. Lentiviral vectors targeting WASp expression to hematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Ther \n                           14, 415\u201328 (2007).","journal-title":"Gene Ther"},{"key":"8550_CR36","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.4049\/jimmunol.177.4.2080","volume":"177","author":"AJ Nauta","year":"2006","unstructured":"Nauta, A. J., Kruisselbrink, A. B., Lurvink, E., Willemze, R. & Fibbe, W. E. Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells. J Immunol \n                           177, 2080\u20132087 (2006).","journal-title":"J Immunol"},{"key":"8550_CR37","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.stem.2013.09.006","volume":"13","author":"ME Bernardo","year":"2013","unstructured":"Bernardo, M. E. & Fibbe, W. E. Mesenchymal stromal cells: sensors and switchers of inflammation. Cell Stem Cell \n                           13, 392\u2013402 (2013).","journal-title":"Cell Stem Cell"},{"key":"8550_CR38","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1210\/me.2013-1286","volume":"28","author":"KK Aenlle","year":"2014","unstructured":"Aenlle, K. K., Curtis, K. M., Roos, B. A. & Howard, G. A. Hepatocyte growth factor and p38 promote osteogenic differentiation of human mesenchymal stem cells. Mol Endocrinol \n                           28, 722\u2013730 (2014).","journal-title":"Mol Endocrinol"},{"key":"8550_CR39","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1111\/j.1582-4934.2011.01407.x","volume":"16","author":"Q Wen","year":"2012","unstructured":"Wen, Q. et al. Change in hepatocyte growth factor concentration promote mesenchymal stem cell mediated osteogenic regeneration. J Cell Mol Med \n                           16, 1260\u20131273 (2012).","journal-title":"J Cell Mol Med"},{"key":"8550_CR40","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jaci.2015.11.028","volume":"138","author":"M Weisser","year":"2016","unstructured":"Weisser, M. et al. Hyperinflammation in patients with chronic granulomatous disease leads to impairment of hematopoietic stem cell functions. J Allergy Clin Immunol \n                           138, 219\u2013228 (2016).","journal-title":"J Allergy Clin Immunol"},{"key":"8550_CR41","doi-asserted-by":"publisher","first-page":"3216","DOI":"10.1182\/blood-2009-03-209221","volume":"114","author":"AV Sauer","year":"2009","unstructured":"Sauer, A. V. et al. ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL\/OPG imbalance and osteoblast insufficiency. Blood \n                           114, 3216\u20133226 (2009).","journal-title":"Blood"},{"key":"8550_CR42","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/mt.2009.26","volume":"17","author":"A Jacome","year":"2009","unstructured":"Jacome, A. et al. Lentiviral-mediated genetic correction of hematopoietic and mesenchymal progenitor cells from Fanconi anemia patients. Mol Ther \n                           17, 1083\u20131092 (2009).","journal-title":"Mol Ther"},{"key":"8550_CR43","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/bjh.13504","volume":"170","author":"M Mantelli","year":"2015","unstructured":"Mantelli, M. et al. Comprehensive characterization of mesenchymal stromal cells from patients with Fanconi anaemia. Br J Haematol \n                           170, 826\u2013836 (2015).","journal-title":"Br J Haematol"},{"key":"8550_CR44","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1016\/j.jcyt.2016.08.011","volume":"18","author":"DM Ingo","year":"2016","unstructured":"Ingo, D. M. et al. Bone marrow-derived CD34- fraction: a rich source of mesenchymal stromal cells for clinical application. Cytotherapy \n                           18, 1560\u20131563 (2016).","journal-title":"Cytotherapy"},{"key":"8550_CR45","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1373\/clinchem.2003.021576","volume":"49","author":"F Carlucci","year":"2003","unstructured":"Carlucci, F. et al. Capillary electrophoresis in diagnosis and monitoring of adenosine deaminase deficiency. Clin Chem \n                           49, 1830\u20131838 (2003).","journal-title":"Clin Chem"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08550-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08550-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08550-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:28:53Z","timestamp":1671784133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08550-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,15]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["8550"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-08550-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2017,8,15]]},"assertion":[{"value":"28 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8153"}}