{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T05:01:56Z","timestamp":1783832516120,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rohto Pharmaceutical Co. Ltd","award":["2020"],"award-info":[{"award-number":["2020"]}]},{"name":"Japanese Ministry of Education, Science, Sports, Culture and Technology","award":["18K09421"],"award-info":[{"award-number":["18K09421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mesenchymal stem cells (MSCs) have been widely used in therapeutic applications for many decades. However, more and more evidence suggests that factors such as the site of origin and pre-implantation treatment have a crucial impact on the result. This study investigates the role of freshly isolated MSCs in the lacrimal gland after allogeneic transplantation. For this purpose, MSCs from transgenic GFP mice were isolated and transplanted into allogeneic and syngeneic recipients. While the syngeneic MSCs maintained a spherical shape, allogeneic MSCs engrafted into the tissue as spindle-shaped cells in the interstitial stroma. Furthermore, the MSCs produced collagen type I in more than 85% to 95% of the detected GFP+ MSCs in the recipients of both models, supposedly contributing to pathogenic fibrosis in allogeneic recipients compared to syngeneic models. These findings indicate that allogeneic MSCs act completely differently from syngeneic MSCs, highlighting the importance of understanding the exact mechanisms behind MSCs.<\/jats:p>","DOI":"10.3390\/ijms22094895","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T11:06:01Z","timestamp":1620212761000},"page":"4895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["MSCs Become Collagen-Type I Producing Cells with Different Phenotype in Allogeneic and Syngeneic Bone Marrow Transplantation"],"prefix":"10.3390","volume":"22","author":[{"given":"Robert Maximilian","family":"Rusch","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinri","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8859-2888","authenticated-orcid":false,"given":"Satoru","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-8578","authenticated-orcid":false,"given":"Eisuke","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-7111","authenticated-orcid":false,"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0992-4862","authenticated-orcid":false,"given":"Shigeto","family":"Shimmura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine 35 Shinanomachi, Shinjuku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1126\/science.161.3836.54","article-title":"Transplantation of marrow to extramedullary sites","volume":"161","author":"Tavassoli","year":"1968","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/00007890-197404000-00001","article-title":"Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo","volume":"17","author":"Friedenstein","year":"1974","journal-title":"Transplantation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/8756-3282(92)90364-3","article-title":"Characterization of cells with osteogenic potential from human marrow","volume":"13","author":"Haynesworth","year":"1992","journal-title":"Bone"},{"key":"ref_4","first-page":"557","article-title":"Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): Implications for therapeutic use","volume":"16","author":"Lazarus","year":"1995","journal-title":"Bone Marrow Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Szaraz, P., Gratch, Y.S., Iqbal, F., and Librach, C.L. (2017). In Vitro Differentiation of Human Mesenchymal Stem Cells into Functional Cardiomyocyte-like Cells. J. Vis. Exp., e55757.","DOI":"10.3791\/55757"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.joms.2007.04.008","article-title":"Adult mesenchymal stem cells: Biological properties, characteristics, and applications in maxillofacial surgery","volume":"65","author":"Shanti","year":"2007","journal-title":"J. Oral Maxillofac. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.cardiores.2006.03.022","article-title":"Collagen synthesis by mesenchymal stem cells and aortic valve interstitial cells in response to mechanical stretch","volume":"71","author":"Ku","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/scrt442","article-title":"Protein synthesis and secretion in human mesenchymal cells derived from bone marrow, adipose tissue and Wharton\u2019s jelly","volume":"5","author":"Amable","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1089\/ten.tea.2012.0279","article-title":"Aligned fibrous scaffolds for enhanced mechanoresponse and tenogenesis of mesenchymal stem cells","volume":"19","author":"Teh","year":"2013","journal-title":"Tissue Eng. Part A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1089\/ten.tec.2010.0513","article-title":"Aligned hybrid silk scaffold for enhanced differentiation of mesenchymal stem cells into ligament fibroblasts","volume":"17","author":"Teh","year":"2011","journal-title":"Tissue Eng. Part C Methods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3389\/fimmu.2013.00201","article-title":"Mesenchymal stem cells in tissue repair","volume":"4","author":"Dimarino","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.1177\/0363546513508744","article-title":"Stem cell therapies for knee cartilage repair: The current status of preclinical and clinical studies","volume":"42","author":"Anderson","year":"2014","journal-title":"Am. J. Sports Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.mad.2007.12.002","article-title":"Age-related changes in human bone marrow-derived mesenchymal stem cells: Consequences for cell therapies","volume":"129","author":"Stolzing","year":"2008","journal-title":"Mech. Ageing Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1634\/stemcells.21-1-105","article-title":"Searching for alternative sources of postnatal human mesenchymal stem cells: Candidate MSC-like cells from umbilical cord","volume":"21","author":"Romanov","year":"2003","journal-title":"Stem Cells"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1634\/stemcells.2004-0058","article-title":"Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta","volume":"22","author":"Scherjon","year":"2004","journal-title":"Stem Cells"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1007\/s10529-016-2050-2","article-title":"Comparison of adult stem cells derived from multiple stem cell niches","volume":"38","author":"Woo","year":"2016","journal-title":"Biotechnol. Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s10616-014-9718-z","article-title":"Isolation, expansion and characterisation of mesenchymal stem cells from human bone marrow, adipose tissue, umbilical cord blood and matrix: A comparative study","volume":"67","author":"Secunda","year":"2015","journal-title":"Cytotechnology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ijom.2015.06.022","article-title":"Comparison of human mesenchymal stem cells derived from bone marrow, synovial fluid, adult dental pulp, and exfoliated deciduous tooth pulp","volume":"45","author":"Isobe","year":"2016","journal-title":"Int. J. Oral Maxillofac. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1186\/s13287-018-0914-1","article-title":"Adipose-derived and bone marrow mesenchymal stem cells: A donor-matched comparison","volume":"9","author":"Fristad","year":"2018","journal-title":"Stem Cell Res. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix elasticity directs stem cell lineage specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"591","DOI":"10.5966\/sctm.2015-0176","article-title":"Massive Clonal Selection and Transiently Contributing Clones during Expansion of Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology","volume":"5","author":"Selich","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/bmt.2010.87","article-title":"Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation","volume":"46","author":"Bernardo","year":"2011","journal-title":"Bone Marrow Transpl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbmt.2005.02.001","article-title":"Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients","volume":"11","author":"Lazarus","year":"2005","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1532\/IJH97.A30409","article-title":"Cotransplantation of marrow stromal cells may prevent lethal graft-versus-host disease in major histocompatibility complex mismatched murine hematopoietic stem cell transplantation","volume":"80","author":"Chung","year":"2004","journal-title":"Int. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e09394","DOI":"10.7554\/eLife.09394","article-title":"MHC-compatible bone marrow stromal\/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model","volume":"5","author":"Ogawa","year":"2016","journal-title":"Elife"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1038\/sj.leu.2404777","article-title":"Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells","volume":"21","author":"Samuelsson","year":"2007","journal-title":"Leukemia"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1034\/j.1600-065X.2002.19007.x","article-title":"The immunogenomics of minor histocompatibility antigens","volume":"190","author":"Roopenian","year":"2002","journal-title":"Immunol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S0167-5699(98)80007-8","article-title":"Much ado about minor histocompatibility antigens","volume":"19","author":"Simpson","year":"1998","journal-title":"Immunol. Today"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1200\/JCO.2010.33.7212","article-title":"Long-term survival and late deaths after allogeneic hematopoietic cell transplantation","volume":"29","author":"Wingard","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbmt.2014.12.001","article-title":"National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report","volume":"21","author":"Pidala","year":"2015","journal-title":"Biol. Blood Marrow Transpl."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1136\/bjo.83.10.1125","article-title":"Dry eye after haematopoietic stem cell transplantation","volume":"83","author":"Ogawa","year":"1999","journal-title":"Br. J. Ophthalmol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1038\/bmt.2012.53","article-title":"Hepatic GVHD leading to cirrhosis after allogeneic hematopoietic SCT","volume":"47","author":"Xhaard","year":"2012","journal-title":"Bone Marrow Transpl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00003495-200363010-00001","article-title":"Intestinal graft-versus-host disease: Mechanisms and management","volume":"63","author":"Takatsuka","year":"2003","journal-title":"Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/sj.bmt.1702383","article-title":"Parotid salivary gland dysfunction in chronic graft-versus-host disease (cGVHD): A longitudinal study in a mouse model","volume":"25","author":"Levy","year":"2000","journal-title":"Bone Marrow Transpl."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4838","DOI":"10.1038\/s41598-017-05099-1","article-title":"Prospectively isolated mesenchymal stem\/stromal cells are enriched in the CD73+ population and exhibit efficacy after transplantation","volume":"7","author":"Suto","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/s41419-019-1569-2","article-title":"Nicotinamide mononucleotide promotes osteogenesis and reduces adipogenesis by regulating mesenchymal stromal cells via the SIRT1 pathway in aged bone marrow","volume":"10","author":"Song","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1084\/jem.20091046","article-title":"Prospective identification, isolation, and systemic transplantation of multipotent mesenchymal stem cells in murine bone marrow","volume":"206","author":"Morikawa","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/7434","article-title":"Ischemia- and cytokine-induced mobilization of bone marrow-derived endothelial progenitor cells for neovascularization","volume":"5","author":"Takahashi","year":"1999","journal-title":"Nat. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10344","DOI":"10.1073\/pnas.181177898","article-title":"Mobilized bone marrow cells repair the infarcted heart, improving function and survival","volume":"98","author":"Orlic","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1038\/s41409-018-0340-0","article-title":"Ocular graft-versus-host disease after hematopoietic cell transplantation: Expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT","volume":"54","author":"Inamoto","year":"2019","journal-title":"Bone Marrow Transplant"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.3389\/fimmu.2020.01338","article-title":"Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers","volume":"11","author":"Cheung","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4593","DOI":"10.1038\/s41598-020-58126-z","article-title":"Syngeneic Mesenchymal Stem Cells Reduce Immune Rejection after Induced Pluripotent Stem Cell-Derived Allogeneic Cardiomyocyte Transplantation","volume":"10","author":"Yoshida","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12100","DOI":"10.1038\/s41598-017-12121-z","article-title":"Membrane particles generated from mesenchymal stromal cells modulate immune responses by selective targeting of pro-inflammatory monocytes","volume":"7","author":"Goncalves","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/scrt75","article-title":"Mesenchymal stem cell effects on T-cell effector pathways","volume":"2","author":"Duffy","year":"2011","journal-title":"Stem Cell Res. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/scrt410","article-title":"Myocardial transfection of hypoxia-inducible factor-1alpha and co-transplantation of mesenchymal stem cells enhance cardiac repair in rats with experimental myocardial infarction","volume":"5","author":"Huang","year":"2014","journal-title":"Stem Cell Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1007\/978-1-4939-3584-0_7","article-title":"Paracrine Mechanisms of Mesenchymal Stem Cells in Tissue Repair","volume":"1416","author":"Gnecchi","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s13287-020-01684-w","article-title":"Bone marrow mesenchymal stem cells improve bone erosion in collagen-induced arthritis by inhibiting osteoclasia-related factors and differentiating into chondrocytes","volume":"11","author":"Gao","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Waterman, R.S., Tomchuck, S.L., Henkle, S.L., and Betancourt, A.M. (2010). A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010088"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.stem.2013.09.006","article-title":"Mesenchymal stromal cells: Sensors and switchers of inflammation","volume":"13","author":"Bernardo","year":"2013","journal-title":"Cell Stem Cell"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:21Z","timestamp":1760162241000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":50,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094895"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094895","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]}}}