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Cited by 46Mesenchymal stem cell researchAngiogenesis and VEGF in CancerHematopoietic Stem Cell Transplantation

Mesenchymal stem/stromal cells enhance engraftment, vasculogenic and pro-angiogenic activities of endothelial colony forming cells in immunocompetent hosts

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Shafiee, Abbas, Patel, Jatin, Lee, James S., Hutmacher, Dietmar W., Fisk, Nicholas M., Khosrotehrani, Kiarash·2017·Scientific Reports
DOI 10.1038/s41598-017-13971-3PMC PMC5648925
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Abstract

Abstract The clinical use of endothelial colony forming cells (ECFC) is hampered by their restricted engraftment. We aimed to assess engraftment, vasculogenic and pro-angiogenic activities of ECFC in immunocompetent (C57BL/6: WT) or immunodeficient (rag1−/−C57BL/6: Rag1) mice. In addition, the impact of host immune system was investigated where ECFC were co-implanted with mesenchymal stem/stromal cells (MSC) from adult bone marrow (AdBM-MSC), fetal bone marrow (fBM-MSC), fetal placental (fPL-MSC), or maternal placental (MPL-MSC). Transplantation of ECFCs in Matrigel plugs resulted in less cell engraftment in WT mice compared to Rag1 mice. Co-implantation with different MSCs resulted in a significant increase in cell engraftment up to 9 fold in WT mice reaching levels of engraftment observed when using ECFCs alone in Rag1 mice but well below levels of engraftment with MSC-ECFC combination in Rag1 recipients. Furthermore, MSCs did not reduce murine splenic T cell proliferation in response to ECFCsin vitro. ECFCs enhanced the murine neo-vascularization through paracrine effect, but with no difference between Rag1 and WT mice. In conclusions, the host adaptive immune system affects the engraftment of ECFCs. MSC co-implantation improves ECFC engraftment and function even in immunocompetent hosts mostly through non-immune mechanisms.

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  • Endothelial cells alone are insufficient in recapitulating blood vessel structures.

    “Considering the importance of pericytes and VSMCs in vasculature, endothelial cells alone are insufficient in recapitulating blood vessel structures.[ 64 , 65 ]”

    From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [64]

    The Results section, “Co-injection with MSCs increases formation of human vessel-like structures” (page unavailable), reports minimal structures after ECFC implantation alone and increased formation with some MSC co-implants. But ECFCs alone still formed vessel-like structures, particularly in immunodeficient mice. The paper therefore supports the benefit of additional cells in its experimental setting, not a general claim that endothelial cells alone cannot recapitulate blood-vessel structures. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Vasculogenic potential of endothelial progenitors is enhanced when combined with a mesenchymal component.

    “Previous studies have shown that the vasculogenic potential of endothelial progenitors is enhanced when combined with a mesenchymal component.[ 64 , 73 ]”

    From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [64]

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Authors
Shafiee, A., Patel, J., Lee, J. S., Hutmacher, D. W., Fisk, N. M., & Khosrotehrani, K.
Affiliations
  • The University of Queensland (AU)
  • Queensland University of Technology (AU)
Corresponding author
Khosrotehrani, Kiarash
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-10-19
Volume
7
Issue
1
Pages
13558-13558
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-017-13971-3
PMC
PMC5648925
OpenAlex
W2763926730
Cited by
46
References
52
Citations by year
2026: 1 · 2025: 2 · 2024: 8 · 2023: 3 · 2022: 3 · 2021: 7 · 2020: 14 · 2019: 6 · 2018: 1 · 2017: 1
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
  • Griffith Research Online (submittedVersion, cc-by)
Funders
  • QIMR Berghofer Medical Research Institute
  • National Heart Foundation of Australia
  • Medical Research Council
  • National Health and Medical Research Council (1023368, 1125290)
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
endothelial colony-forming cells, mesenchymal stem cells, cell engraftment, angiogenesis, vasculogenesis, host immune system, Rag1 knockout mice, co-implantation, paracrine effects, neovascularization, T cell proliferation, bone marrow-derived MSCs, immunocompetent patient
MeSH terms
Animals, Bone Marrow Cells, Cells, Cultured, Female, Immune System, Mice, Inbred C57BL, Placenta, Pregnancy, T-Lymphocytes, Immunocompromised Host, Homeodomain Proteins, Neovascularization, Physiologic, Paracrine Communication, Endothelial Cells, Mesenchymal Stem Cell Transplantation, Mice, Mesenchymal Stem Cells

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