, Volume 15, Issue 3, pp 443–455 | Cite as

Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells

  • Ruei-Zeng Lin
  • Rafael Moreno-Luna
  • Bin Zhou
  • William T. Pu
  • Juan M. Melero-MartinEmail author
Original Paper


Mesenchymal stem cells (MSCs) can generate multiple end-stage mesenchymal cell types and constitute a promising population of cells for regenerative therapies. Additionally, there is increasing evidence supporting other trophic activities of MSCs, including the ability to enable formation of vasculature in vivo. Although MSCs were originally isolated from the bone marrow, the presence of these cells in the stromal vascular fraction of multiple adult tissues has been recently recognized. However, it is unknown whether the capacity to modulate vasculogenesis is ubiquitous to all MSCs regardless of their tissue of origin. Here, we demonstrated that tissue-resident MSCs isolated from four distinct tissues have equal capacity to modulate endothelial cell function, including formation of vascular networks in vivo. MSCs were isolated from four murine tissues, including bone marrow, white adipose tissue, skeletal muscle, and myocardium. In culture, all four MSC populations secreted a plethora of pro-angiogenic factors that unequivocally induced proliferation, migration, and tube formation of endothelial colony-forming cells (ECFCs). In vivo, co-implantation of MSCs with ECFCs into mice generated an extensive network of blood vessels with ECFCs specifically lining the lumens and MSCs occupying perivascular positions. Importantly, there were no differences among all four MSCs evaluated. Our studies suggest that the capacity to modulate the formation of vasculature is a ubiquitous property of all MSCs, irrespective of their original anatomical location. These results validate multiple tissues as potential sources of MSCs for future cell-based vascular therapies.


Mesenchymal stem cells Endothelial cell Vasculogenesis Pericytes Endothelial progenitor cells 



Mouse dermal endothelial cells (mDEC) were kindly provided by Dr. Andrew C. Dudley (University of North Carolina at Chapel Hill). Histology was supported by the Specialized Research Pathology Cores, Longwood Facility of the Dana-Farber/Harvard Cancer Center. This work was supported by a grant from the National Institutes of Health (R00EB009096) to J.M.-M, and by grants from the Instituto de Salud Carlos III and Junta de Andalucía, Consejería de Salud to R.M.-L.

Conflict of interest

The authors have declared that no conflict of interest exists.

Supplementary material

10456_2012_9272_MOESM1_ESM.pdf (19 kb)
Supplementary material 1 (PDF 18 kb)


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Ruei-Zeng Lin
    • 5
  • Rafael Moreno-Luna
    • 2
    • 5
  • Bin Zhou
    • 3
    • 4
  • William T. Pu
    • 3
  • Juan M. Melero-Martin
    • 1
    Email author
  1. 1.Department of Cardiac SurgeryChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA
  2. 2.Unidad Clínico-Experimental de Riesgo Vascular (UCAMI-UCERV), Servicio de Medicina InternaHospital Universitario Virgen del Rocío, and Instituto de Biomedicina de Sevilla (IBiS)SevilleSpain
  3. 3.Department of CardiologyChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA
  4. 4.Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  5. 5.Department of Cardiac SurgeryChildren’s Hospital Boston, Harvard Medical SchoolBostonUSA

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