Skip to main content

Advertisement

Log in

Sprouting angiogenesis in human midterm uterus and fallopian tube is guided by endothelial tip cells

  • Original article
  • Published:
Anatomical Science International Aims and scope Submit manuscript

Abstract

Five samples of human midterm fetal uterus and fallopian tube (four donor bodies) were used to assess whether or not processes of angiogenesis are guided by endothelial tip cells (ETCs), and if cytokine-receptors, such as CD117/c-kit and PDGFR-α, are expressed in the microenvironment of the endothelial tubes. CD34 labeled microvessels in the uterine wall (myometrium and endometrium) and in the wall of the uterine (fallopian) tube, and accurately identified ETCs in both organs. We conclude that sprouting angiogenesis in the developing human female tract is guided by ETCs. Moreover, CD117/c-kit antibodies labeled mural networks of pericytes, α-SMA-positive and desmin-negative, related to the endometrial (but not myometrial) microvessels, and similar labeling was identified in the wall of the uterine tube. PDGFR-α positive labeling, stromal and pericytary, was also found. Thus, sprouting angiogenesis in human fetal genital organs appears to be guided by tip cells and is influenced by tyrosine kinase receptor signaling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1a–f
Fig. 2a,b
Fig. 3

Similar content being viewed by others

References

  • Adams RH, Eichmann A (2010) Axon guidance molecules in vascular patterning. Cold Spring Harb Perspect Biol 2:a001875

    Article  PubMed  Google Scholar 

  • Cai X, Lin Y, Friedrich CC et al (2009) Bone marrow derived pluripotent cells are pericytes which contribute to vascularization. Stem Cell Rev 5:437–445

    Article  PubMed  Google Scholar 

  • Cao R, Brakenhielm E, Li X et al (2002) Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFR-alphaalpha and -alphabeta receptors. FASEB J 16:1575–1583

    Article  PubMed  CAS  Google Scholar 

  • Crisan M, Corselli M, Chen WC, Peault B (2012) Perivascular cells for regenerative medicine. J Cell Mol Med. doi: 10.1111/j.1582-4934.2012.01617.x

  • Dentelli P, Rosso A, Balsamo A et al (2007) C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood 109:4264–4271

    Article  PubMed  CAS  Google Scholar 

  • Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314:15–23

    Article  PubMed  Google Scholar 

  • Gerhardt H, Betsholtz C (2005) How do endothelial cells orientate? EXS 94:3–15

    PubMed  Google Scholar 

  • Greenberg JI, Shields DJ, Barillas SG et al (2008) A role for VEGF as a negative regulator of pericyte function and vessel maturation. Nature 456:809–813

    Article  PubMed  CAS  Google Scholar 

  • Hall AP (2006) Review of the pericyte during angiogenesis and its role in cancer and diabetic retinopathy. Toxicol Pathol 34:763–775

    Article  PubMed  CAS  Google Scholar 

  • Hellstrom M, Kalen M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055

    PubMed  CAS  Google Scholar 

  • Jindatip D, Fujiwara K, Kouki T, Yashiro T (2012) Transmission and scanning electron microscopy study of the characteristics and morphology of pericytes and novel desmin-immunopositive perivascular cells before and after castration in rat anterior pituitary gland. Anat Sci Int 87:165–173

    Google Scholar 

  • Melo SA, Kalluri R (2012) Angiogenesis is controlled by miR-27b associated with endothelial tip cells. Blood 119:2439–2440

    Article  PubMed  CAS  Google Scholar 

  • Morikawa S, Ezaki T (2011) Phenotypic changes and possible angiogenic roles of pericytes during wound healing in the mouse skin. Histol Histopathol 26:979–995

    PubMed  Google Scholar 

  • Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM (2002) Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. Am J Pathol 160:985–1000

    Article  PubMed  Google Scholar 

  • Nehls V, Drenckhahn D (1991) Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J Cell Biol 113:147–154

    Article  PubMed  CAS  Google Scholar 

  • Roskoski R Jr (2007) Sunitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun 356:323–328

    Article  PubMed  CAS  Google Scholar 

  • Siemerink MJ, Klaassen I, Vogels IM, Griffioen AW, van Noorden CJ, Schlingemann RO (2012) CD34 marks angiogenic tip cells in human vascular endothelial cell cultures. Angiogenesis 15:151–163

    Article  PubMed  CAS  Google Scholar 

  • Song S, Ewald AJ, Stallcup W, Werb Z, Bergers G (2005) PDGFRbeta+ perivascular progenitor cells in tumours regulate pericyte differentiation and vascular survival. Nat Cell Biol 7:870–879

    Article  PubMed  CAS  Google Scholar 

  • Stanescu R, Didilescu AC, Jianu AM, Rusu MC (2012) Angiogenesis in the reparatory mucosa of the mandibular edentulous ridge is driven by endothelial tip cells. Rom J Morphol Embryo 53:375–378

    Google Scholar 

  • Stefansson IM, Salvesen HB, Akslen LA (2006) Vascular proliferation is important for clinical progress of endometrial cancer. Cancer Res 66:3303–3309

    Article  PubMed  CAS  Google Scholar 

  • Suciu LC, Popescu BO, Kostin S, Popescu LM (2012) Platelet-derived growth factor receptor-beta-positive telocytes in skeletal muscle interstitium. J Cell Mol Med 16:701–707

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

M.C.R. was supported in this study by the Sectoral Operational Programme Human Resources Development (SOP HRD), financed from the European Social Fund and by the Romanian Government under the contract number POSDRU/89/1.5/S/64153.

Conflict of interest

The authors confirm that there are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. C. Rusu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rusu, M.C., Motoc, A.G.M., Pop, F. et al. Sprouting angiogenesis in human midterm uterus and fallopian tube is guided by endothelial tip cells. Anat Sci Int 88, 25–30 (2013). https://doi.org/10.1007/s12565-012-0154-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12565-012-0154-x

Keywords

Navigation