Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells

Le Blanc, Katarina; Rasmusson, Ida; Sundberg, Berit; Götherström, Cecilia; Hassan, Moustapha; Uzunel, Mehmet; Ringdén, Olle

doi:10.1016/s0140-6736(04)16104-7

Cited by 2,734Hematopoietic Stem Cell TransplantationMesenchymal stem cell researchPluripotent Stem Cells Research

Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells

Le Blanc, Katarina, Rasmusson, Ida, Sundberg, Berit, Götherström, Cecilia, Hassan, Moustapha, Uzunel, Mehmet, Ringdén, Olle·2004·The Lancet

DOI 10.1016/s0140-6736(04)16104-7

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Abstract

Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.

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Clinical applications involving systemic administration of MSCs require a large number of cells (1-10 × 106 cells/kg) to demonstrate therapeutic efficacy.
“Clinical applications involving systemic administration of MSCs require a large number of cells (1–10 × 106 cells/kg) to demonstrate a therapeutic efficacy [27–29].”
From Short-term physiological hypoxia potentiates the therapeutic function of mesenchymal stem cells (2018) · cites this paper as [28]

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Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue
Kern, S., Eichler, H., Stoeve, J., Klüter, H., & Bieback, K. (2006) · STEM CELLS · doi:10.1634/stemcells.2005-0342 · Cited by 3,370 · see citing works
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Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A. I., Zhao, R. C., & Shi, Y. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2007.11.014 · Cited by 2,101 · see citing works
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Holzwarth, C., Vaegler, M., Gieseke, F., Pfister, S. M., Handgretinger, R., Kerst, G., & Müller, I. (2010) · BMC Cell Biology · doi:10.1186/1471-2121-11-11 · Cited by 314 · see citing works
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Stroncek, D. F., Jin, P., McKenna, D. H., Takanashi, M., Fontaine, M. J., Pati, S., Schäfer, R., Peterson, E., Benedetti, E., & Reems, J.-A. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00458 · Cited by 59 · see citing works
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Liu, Y., Kou, X., Chen, C., Yu, W., Su, Y., Kim, Y., Shi, S., & Liu, Y. (2016) · Stem Cells · doi:10.1002/stem.2392 · Cited by 61 · see citing works
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Tsang, K. S., Ng, C. P. S., Zhu, X. L., Wong, G. K. C., Lu, G., Ahuja, A. T., Wong, K. S. L., Ng, H. K., & Poon, W. S. (2017) · World Journal of Stem Cells · doi:10.4252/wjsc.v9.i8.133 · Cited by 49 · see citing works
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Ragni, E., Montemurro, T., Montelatici, E., Lavazza, C., Viganò, M., Rebulla, P., Giordano, R., & Lazzari, L. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.04.002 · Cited by 48 · see citing works
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Horwitz, E. M., Andreef, M., & Frassoni, F. (2007) · Biology of Blood and Marrow Transplantation · doi:10.1016/j.bbmt.2006.10.016 · Cited by 31 · see citing works
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Schricker, B. R., Miller, D. D., Rasmussen, R. R., et al. (1981) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/34.10.2257 · Cited by 110 · see citing works
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Mangır, N., Akbal, C., Tarcan, T., Şimşěk, F., & Türkeri, L. (2014) · International Journal of Urology · doi:10.1111/iju.12585 · Cited by 32 · see citing works
Mesenchymal Stem/Stromal Cells: ASSESSING THE SAFETY AND TOXICITY OF VERY HIGH DOSES OF ALLOGENEIC HUMAN UMBILICAL CORD-DERIVED MESENCHYMAL STEM CELLS
Chin, S. P., Mansor, N., & Cheong, S. (2023) · Cytotherapy · doi:10.1016/s1465-3249(23)00202-5 · Cited by 1 · see citing works
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Chen, J.-Y., Chen, W., Cai, H.-X., et al. (1993) · Journal of Photochemistry and Photobiology B Biology · doi:10.1016/1011-1344(93)80069-l · Cited by 8 · see citing works
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Dososaputro, I., Hoekstra, L. T., Rahmania, D., & Perdanakusuma, D. S. (2017) · Journal of Stem Cell Research & Therapy · doi:10.4172/2157-7633.1000398 · Cited by 2 · see citing works

Authors: Le Blanc, K., Rasmusson, I., Sundberg, B., Götherström, C., Hassan, M., Uzunel, M., & Ringdén, O.
Affiliations: Karolinska Institutet (SE)
ORCID: Sundberg, Berit
Hassan, Moustapha
Uzunel, Mehmet
Ringdén, Olle
Venue: The Lancet
Publisher: Elsevier BV
Published: 2004-05
Volume: 363
Issue: 9419
Pages: 1439-1441
ISSN: 0099-5355 (ISSN-L)
0140-6736
DOI: 10.1016/s0140-6736(04)16104-7
OpenAlex: W1982408656
Cited by: 2,734
References: 4
Citations by year: 2026: 29 · 2025: 50 · 2024: 45 · 2023: 86 · 2022: 71 · 2021: 107 · 2020: 118 · 2019: 96 · 2018: 104 · 2017: 119 · 2016: 133 · 2015: 157 · 2014: 159 · 2013: 212 · 2012: 193
FWCI: 71.91
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: The Lancet (publishedVersion)
PubMed (publishedVersion)
Funders: Swedish Cancer Foundation
Cancerfonden
Cancerföreningen i Stockholm
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Keywords: acute graft-versus-host disease, mesenchymal stem cells, haploidentical transplantation, immunosuppression, bone marrow-derived stem cells, skin graft rejection
MeSH terms: Acute Disease, Adult, Child, Female, Graft vs Host Disease, Haploidy, Humans, Immunosuppression Therapy, Intestinal Mucosa, Lymphocyte Culture Test, Mixed, Male, Transplantation, Homologous, In Situ Hybridization, Fluorescence, Transplantation Chimera, Chromosomes, Human, X, Chromosomes, Human, Y, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells

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Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells

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