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Cited by 25Mesenchymal stem cell researchPluripotent Stem Cells ResearchHematopoietic Stem Cell Transplantation

Mesenchymal Stem/Stromal Cells Derived from Induced Pluripotent Stem Cells Support CD34posHematopoietic Stem Cell Propagation and Suppress Inflammatory Reaction

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Moslem, Mohsen, Eberle, Irina, Weber, Iuliia, Henschler, Reinhard, Cantz, Tobias·2015·Stem Cells International
DOI 10.1155/2015/843058PMC PMC4491576
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Abstract

Mesenchymal stem/stromal cells (MSCs) represent a promising cell source for research and therapeutic applications, but their restricted ex vivo propagation capabilities limit putative applications. Substantial self-renewing of stem cells can be achieved by reprogramming cells into induced pluripotent stem cells (iPSCs) that can be easily expanded as undifferentiated cells even in mass culture. Here, we investigated a differentiation protocol enabling the generation and selection of human iPSC-derived MSCs exhibiting relevant surface marker expression profiles (CD105 and CD73) and functional characteristics. We generated such iPSC-MSCs from fibroblasts and bone marrow MSCs utilizing two different reprogramming constructs. All such iPSC-MSCs exhibited the characteristics of normal bone marrow-derived (BM) MSCs. In direct comparison to BM-MSCs our iPSC-MSCs exhibited a similar surface marker expression profile but shorter doubling times without reaching senescence within 20 passages. Considering functional capabilities, iPSC-MSCs provided supportive feeder layer for CD34+hematopoietic stem cells’ self-renewal and colony forming capacities. Furthermore, iPSC-MSCs gained immunomodulatory function to suppress CD4+cell proliferation, reduce proinflammatory cytokines in mixed lymphocyte reaction, and increase regulatory CD4+/CD69+/CD25+T-lymphocyte population. In conclusion, we generated fully functional MSCs from various iPSC lines irrespective of their starting cell source or reprogramming factor composition and we suggest that such iPSC-MSCs allow repetitive cell applications for advanced therapeutic approaches.

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  • Antibody specificity for FACS was validated using iPSCs negative for CD73 and CD105 and THP1 cells negative for CD90.

    “iPSC and THP1 cells were used to validate the specificity of antibodies (Supplementary Figure S1D, E), with iPSCs negative for CD73 and CD105 and THP1 cells negative for CD90 (Moslem et al., 2015; Holken and Teusch, 2023).”

    From APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells (2026) · cites this paper as Moslem et al., 2015

    Methods §2.4 describes FACS antibody staining and says nonspecific fluorescence was assessed with isotype-matched antibodies, not with iPSCs or THP1 cells. Results §3.2 reports CD73 and CD105 expression in differentiated iPSC-MSCs but does not establish that undifferentiated iPSCs are negative for either marker. A search for THP1 and CD90 antibody-validation controls found no supporting passage in our copy. (LLM, conf=0.74)

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Research works printed but not linked: 54

  1. [1]Sutton M. T. Bonfield T. L. Stem cells: innovations in clinical applications Stem Cells International 2014 2014 9 516278 10.1155/2014/516278 PMC4121181 25120571 · DOI
  2. [2]Ludwig A. Saffrich R. Eckstein V. Functional potentials of human hematopoietic progenitor cells are maintained by mesenchymal stromal cells and not impaired by plerixafor Cytotherapy 2014 16 1 111 121 10.1016/j.jcyt.2013.07.007 2-s2.0-84890958770 24119647 · DOI
  3. [3]Oodi A. Noruzinia M. Roudkenar M. H. Expression of P16 cell cycle inhibitor in human cord blood CD34+ expanded cells following co-culture with bone marrow-derived mesenchymal stem cells Hematology 2012 17 6 334 340 10.1179/1607845412y.0000000009 2-s2.0-84869750388 22989929 · DOI
  4. [4]Sato K. Ozaki K. Oh I. Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells Blood 2007 109 1 228 234 10.1182/blood-2006-02-002246 2-s2.0-33846006154 16985180 · DOI
  5. [5]Le Blanc K. Rasmusson I. Götherström C. Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes Scandinavian Journal of Immunology 2004 60 3 307 315 10.1111/j.0300-9475.2004.01483.x 2-s2.0-4344683220 15320889 · DOI
  6. [6]Ren G. Zhang L. Zhao X. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide Cell Stem Cell 2008 2 2 141 150 10.1016/j.stem.2007.11.014 2-s2.0-38649105374 18371435 · DOI · Paper page
  7. [7]Yu J. Vodyanik M. A. Smuga-Otto K. Induced pluripotent stem cell lines derived from human somatic cells Science 2007 318 5858 1917 1920 10.1126/science.1151526 2-s2.0-36749043230 18029452 · DOI · Paper page
  8. [8]Groß B. Sgodda M. Rasche M. Improved generation of patient-specific induced pluripotent stem cells using a chemically-defined and matrigel-based approach Current Molecular Medicine 2013 13 5 765 776 10.2174/1566524011313050008 2-s2.0-84881336016 23642058 · DOI
  9. [9]Zaehres H. Kögler G. Arauzo-Bravo M. J. Induction of pluripotency in human cord blood unrestricted somatic stem cells Experimental Hematology 2010 38 9 809 818 10.1016/j.exphem.2010.05.009 2-s2.0-77955486402 20541586 · DOI
  10. [10]Takahashi K. Tanabe K. Ohnuki M. Induction of pluripotent stem cells from adult human fibroblasts by defined factors Cell 2007 131 5 861 872 10.1016/j.cell.2007.11.019 2-s2.0-36248966518 18035408 · DOI · Paper page
  11. [11]Eberle I. Moslem M. Henschler R. Cantz T. Engineered MSCs from patient-specific iPS cells Mesenchymal Stem Cells—Basics and Clinical Application II 2013 130 Berlin, Germany Springer 1 17 Advances in Biochemical Engineering/Biotechnology 10.1007/10_2012_156 22915200 · DOI
  12. [12]Sánchez L. Gutierrez-Aranda I. Ligero G. Enrichment of human ESC-derived multipotent mesenchymal stem cells with immunosuppressive and anti-inflammatory properties capable to protect against experimental inflammatory bowel disease Stem Cells 2011 29 2 251 262 10.1002/stem.569 2-s2.0-79952133599 21732483 · DOI
  13. [13]Sun Y.-Q. Deng M.-X. He J. Human pluripotent stem cell-derived mesenchymal stem cells prevent allergic airway inflammation in mice Stem Cells 2012 30 12 2692 2699 10.1002/stem.1241 2-s2.0-84870362545 22987325 PMC3549478 · DOI
  14. [14]Moslem M. Valojerdi M. R. Pournasr B. Muhammadnejad A. Baharvand H. Therapeutic potential of human induced pluripotent stem cell-derived mesenchymal stem cells in mice with lethal fulminant hepatic failure Cell Transplantation 2013 22 10 1785 1799 10.3727/096368912x662462 2-s2.0-84884697664 23394436 · DOI
  15. [15]Lian Q. Zhang Y. Zhang J. Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice Circulation 2010 121 9 1113 1123 10.1161/CIRCULATIONAHA.109.898312 2-s2.0-77949350004 20176987 · DOI
  16. [16]Jung Y. Bauer G. Nolta J. A. Concise review: induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products Stem Cells 2012 30 1 42 47 10.1002/stem.727 2-s2.0-84855407207 21898694 PMC3784250 · DOI
  17. [17]Hynes K. Menicanin D. Han J. Mesenchymal stem cells from iPS cells facilitate periodontal regeneration Journal of Dental Research 2013 92 9 833 839 10.1177/0022034513498258 2-s2.0-84882806357 23884555 · DOI
  18. [18]Wagner W. Wein F. Seckinger A. Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood Experimental Hematology 2005 33 11 1402 1416 10.1016/j.exphem.2005.07.003 2-s2.0-27544441193 16263424 · DOI
  19. [19]Torensma R. Prins H.-J. Schrama E. The impact of cell source, culture methodology, culture location, and individual donors on gene expression profiles of bone marrow-derived and adipose-derived stromal cells Stem Cells and Development 2013 22 7 1086 1096 10.1089/scd.2012.0384 2-s2.0-84875938896 23145933 PMC3608038 · DOI
  20. [20]Pachón-Peña G. Yu G. Tucker A. Stromal stem cells from adipose tissue and bone marrow of age-matched female donors display distinct immunophenotypic profiles Journal of Cellular Physiology 2011 226 3 843 851 10.1002/jcp.22408 2-s2.0-78650667231 20857424 PMC4340690 · DOI
  21. [21]Shen B. Wei A. Whittaker S. The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro Journal of Cellular Biochemistry 2010 109 2 406 416 10.1002/jcb.22412 2-s2.0-74949118565 19950204 · DOI
  22. [22]Zou L. Zou X. Chen L. Multilineage differentiation of porcine bone marrow stromal cells associated with specific gene expression pattern Journal of Orthopaedic Research 2008 26 1 56 64 10.1002/jor.20467 2-s2.0-38049095046 17676606 · DOI
  23. [23]Karystinou A. Dell'Accio F. Kurth T. B. A. Distinct mesenchymal progenitor cell subsets in the adult human synovium Rheumatology 2009 48 9 1057 1064 10.1093/rheumatology/kep192 2-s2.0-70349784736 19605375 · DOI
  24. [24]Warlich E. Kuehle J. Cantz T. Lentiviral vector design and imaging approaches to visualize the early stages of cellular reprogramming Molecular Therapy 2011 19 4 782 789 10.1038/mt.2010.314 2-s2.0-79953310912 21285961 PMC3070104 · DOI
  25. [25]Haase A. Olmer R. Schwanke K. Generation of induced pluripotent stem cells from human cord blood Cell Stem Cell 2009 5 4 434 441 10.1016/j.stem.2009.08.021 2-s2.0-70349452213 19796623 · DOI
  26. [26]Rüster B. Göttig S. Ludwig R. J. Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells Blood 2006 108 12 3938 3944 10.1182/blood-2006-05-025098 2-s2.0-33845277598 16896152 · DOI
  27. [27]Kern S. Eichler H. Stoeve J. Klüter H. Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue Stem Cells 2006 24 5 1294 1301 10.1634/stemcells.2005-0342 2-s2.0-33745437684 16410387 · DOI · Paper page
  28. [28]Sgodda M. Möbus S. Hoepfner J. Improved hepatic differentiation strategies for human induced pluripotent stem cells Current Molecular Medicine 2013 13 5 842 855 10.2174/1566524011313050015 2-s2.0-84881341670 23642065 · DOI
  29. [29]Dominici M. Le Blanc K. Mueller I. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement Cytotherapy 2006 8 4 315 317 10.1080/14653240600855905 2-s2.0-33747713246 16923606 · DOI · Paper page
  30. [30]DiMarino A. M. Caplan A. I. Bonfield T. L. Mesenchymal stem cells in tissue repair Frontiers in Immunology 2013 4, article 102 10.3389/fimmu.2013.00201 2-s2.0-84883729239 PMC3761350 24027567 · DOI
  31. [32]Radtke C. L. Nino-Fong R. Esparza Gonzalez B. P. Stryhn H. McDuffee L. A. Characterization and osteogenic potential of equine muscle tissue- and periosteal tissue-derived mesenchymal stem cells in comparison with bone marrow- and adipose tissue-derived mesenchymal stem cells American Journal of Veterinary Research 2013 74 5 790 800 23627394
  32. [33]Morrison S. J. Spradling A. C. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life Cell 2008 132 4 598 611 10.1016/j.cell.2008.01.038 2-s2.0-39149144034 18295578 PMC4505728 · DOI
  33. [34]Wilson A. Trumpp A. Bone-marrow haematopoietic-stem-cell niches Nature Reviews Immunology 2006 6 2 93 106 10.1038/nri1779 2-s2.0-33644827383 16491134 · DOI
  34. [35]Arai F. Hirao A. Ohmura M. Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche Cell 2004 118 2 149 161 10.1016/j.cell.2004.07.004 2-s2.0-3242669145 15260986 · DOI
  35. [36]Orford K. W. Scadden D. T. Deconstructing stem cell self-renewal: genetic insights into cell-cycle regulation Nature Reviews Genetics 2008 9 2 115 128 10.1038/nrg2269 2-s2.0-38349132624 18202695 · DOI · Paper page
  36. [37]Zhang J. Niu C. Ye L. Identification of the haematopoietic stem cell niche and control of the niche size Nature 2003 425 6960 836 841 10.1038/nature02041 2-s2.0-0242363225 14574412 · DOI
  37. [38]Sugiyama T. Kohara H. Noda M. Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches Immunity 2006 25 6 977 988 10.1016/j.immuni.2006.10.016 2-s2.0-33845445939 17174120 · DOI
  38. [39]Milazzo L. Vulcano F. Barca A. Cord blood CD34+ cells expanded on Wharton's jelly multipotent mesenchymal stromal cells improve the hematopoietic engraftment in NOD/SCID mice European Journal of Haematology 2014 93 5 384 391 10.1111/ejh.12363 24797266 · DOI
  39. [40]Nishiwaki S. Nakayama T. Saito S. Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis International Journal of Hematology 2012 96 3 295 300 10.1007/s12185-012-1140-8 2-s2.0-84867009276 22782260 · DOI
  40. [41]Jing D. Fonseca A.-V. Alakel N. Hematopoietic stem cells in co-culture with mesenchymal stromal cells—modeling the niche compartments in vitro Haematologica 2010 95 4 542 550 10.3324/haematol.2009.010736 2-s2.0-77950639113 20145267 PMC2857183 · DOI
  41. [42]Sharma M. B. Limaye L. S. Kale V. P. Mimicking the functional hematopoietic stem cell niche in vitro: recapitulation of marrow physiology by hydrogel-based three-dimensional cultures of mesenchymal stromal cells Haematologica 2012 97 5 651 660 10.3324/haematol.2011.050500 2-s2.0-84860593391 22058199 PMC3342965 · DOI
  42. [43]Wagner W. Roderburg C. Wein F. Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors Stem Cells 2007 25 10 2638 2647 10.1634/stemcells.2007-0280 2-s2.0-35348826635 17615262 · DOI
  43. [44]Keating A. Mesenchymal stromal cells: new directions Cell Stem Cell 2012 10 6 709 716 10.1016/j.stem.2012.05.015 2-s2.0-84862534451 22704511 · DOI · Paper page
  44. [45]Uccelli A. Moretta L. Pistoia V. Mesenchymal stem cells in health and disease Nature Reviews Immunology 2008 8 9 726 736 10.1038/nri2395 2-s2.0-50249158511 19172693 · DOI
  45. [46]Blazar B. R. Murphy W. J. Abedi M. Advances in graft-versus-host disease biology and therapy Nature Reviews Immunology 2012 12 6 443 458 10.1038/nri3212 2-s2.0-84861576998 PMC3552454 22576252 · DOI
  46. [47]Liu Y. Yang R. Shi S. Systemic infusion of mesenchymal stem cells improves cell-based bone regeneration via upregulation of regulatory T cells Tissue Engineering Part A 2015 21 3-4 498 509 10.1089/ten.tea.2013.0673 25159486 PMC4333317 · DOI
  47. [48]Giuliani M. Oudrhiri N. Noman Z. M. Human mesenchymal stem cells derived from induced pluripotent stem cells down-regulate NK-cell cytolytic machinery Blood 2011 118 12 3254 3262 10.1182/blood-2010-12-325324 2-s2.0-80053217109 21803852 · DOI
  48. [49]Meisel R. Zibert A. Laryea M. Göbel U. Däubener W. Dilloo D. Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation Blood 2004 103 12 4619 4621 10.1182/blood-2003-11-3909 2-s2.0-2942595706 15001472 · DOI
  49. [50]Tse W. T. Pendleton J. D. Beyer W. M. Egalka M. C. Guinan E. C. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation Transplantation 2003 75 3 389 397 10.1097/01.tp.0000045055.63901.a9 2-s2.0-0037442264 12589164 · DOI
  50. [51]Krampera M. Glennie S. Dyson J. Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide Blood 2003 101 9 3722 3729 10.1182/blood-2002-07-2104 2-s2.0-0038204193 12506037 · DOI
  51. [52]Saldanha-Araujo F. Haddad R. Malmegrim de Farias K. C. R. Mesenchymal stem cells promote the sustained expression of CD69 on activated T lymphocytes: roles of canonical and non-canonical NF-κB signalling Journal of Cellular and Molecular Medicine 2012 16 6 1232 1244 10.1111/j.1582-4934.2011.01391.x 2-s2.0-84861546167 21777379 PMC3823077 · DOI
  52. [53]Luz-Crawford P. Kurte M. Bravo-Alegría J. Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells Stem Cell Research & Therapy 2013 4 3, article 65 10.1186/scrt216 2-s2.0-84878401681 PMC3706898 23734780 · DOI
  53. [54]Nazarov C. Surdo J. L. Bauer S. R. Wei C.-H. Assessment of immunosuppressive activity of human mesenchymal stem cells using murine antigen specific CD4 and CD8 T cells in vitro Stem Cell Research and Therapy 2013 4 5, article 128 10.1186/scrt339 2-s2.0-84886871106 PMC3854780 24406271 · DOI
  54. [55]Dorronsoro A. Ferrin I. Salcedo J. M. Human mesenchymal stromal cells modulate T-cell responses through TNF-alpha-mediated activation of NF-kappaB European Journal of Immunology 2014 44 2 480 488 10.1002/eji.201343668 2-s2.0-84893577574 24307058 · DOI

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Sorted by citations

Authors
Moslem, M., Eberle, I., Weber, I., Henschler, R., & Cantz, T.
Affiliations
  • LMU Klinikum (DE)
  • Medizinische Hochschule Hannover (DE)
  • German Red Cross (DE)
Corresponding author
  • Henschler, Reinhard
  • Cantz, Tobias
ORCID
Venue
Stem Cells International
Publisher
Hindawi Limited
Published
2015
Volume
2015
Pages
1-14
ISSN
  • 1687-966X (ISSN-L)
  • 1687-9678
DOI
10.1155/2015/843058
PMC
PMC4491576
OpenAlex
W1505439893
Cited by
25
References
1
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 1 · 2021: 1 · 2019: 4 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 1
FWCI
2.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cells International (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (EXC62/2, Exc-62)
  • Gottfried Wilhelm Leibniz Universität Hannover
  • Medizinischen Hochschule Hannover
  • Leibniz-Gemeinschaft
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
mesenchymal stem cells, induced pluripotent stem cells, hematopoietic stem cells, CD34+ cells, self-renewal, immunomodulation, regulatory T cells, CD4+ T cell proliferation, inflammatory cytokines, bone marrow-derived MSCs, fibroblast reprogramming, cell expansion, CD105, CD73

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