Infantile haemangioma expresses embryonic stem cell markers
- Tinte Itinteang1,2,3,
- Swee T Tan1,2,3,4,
- Helen D Brasch5,
- Ryan Steel1,
- Heather A Best1,
- Anasuya Vishvanath1,
- Jun Jia2,
- Darren J Day1,2,3
- 1School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand
- 2Gillies McIndoe Research Institute, Wellington, New Zealand
- 3Centre for the Study & Treatment of Vascular Birthmarks, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, Wellington, New Zealand
- 4University of Otago, Wellington, New Zealand
- 5Department of Pathology, Hutt Hospital, Wellington, New Zealand
- Correspondence to Professor Swee T Tan, Wellington Regional Plastic, Maxillofacial and Burns Unit, Hutt Hospital, High Street, Private Bag 31-907, Lower Hutt, New Zealand;
Contributors STT, TI, HDB and DJD were involved in the conception and design of the study, and analysis and interpretation of the data. RS, AV and JJ carried out quantitative reverse transcription PCR and were involved in interpretation of the data. TI and HAB carried out immunohistochemical staining and were involved in interpretation of the data. TI, STT and DJD drafted and revised the manuscript. TI, STT, HDB, RS, HAB, JJ and DJD commented on and approved the version of the manuscript to be published. STT and DJD are equal senior authors.
- Accepted 1 November 2011
- Published Online First 23 March 2012
Background The origin of infantile haemangioma (IH) remains enigmatic. A primitive mesodermal phenotype origin of IH with the ability to differentiate down erythropoietic and terminal mesenchymal lineages has recently been demonstrated.
Aims To investigate the expression of human embryonic stem cell (hESC) markers in IH and to determine whether IH-derived cells have the functional capacity to form teratoma in vivo.
Methods Immunohistochemical staining and quantitative reverse transcription PCR were used to investigate the expression of hESC markers in IH biopsies. The ability of cells derived from proliferating IH to form teratomas in a mouse xenograft model was investigated.
Results The hESC markers, Oct-4, STAT-3 and stage-specific embryonic antigen 4 were collectively expressed on the endothelium of proliferating IH lesions, whereas Nanog was not. Nanog was expressed by cells in the interstitium and these cells did not express Oct-4, stage-specific embryonic antigen 4 or STAT-3. Proliferating IH-derived cells were unable to form teratomas in severely compromised immunodeficient/non-obese diabetic mice.
Conclusion The novel expression of hESC on two different populations of cells in proliferating IH and their inability to form teratomas in vivo infer the presence of a primitive cellular origin for IH downstream from hESC.
- biological sciences
- cancer research
- cancer stem cells
- cell biology
- embryonic stem cells
- haemogenic endothelium
- head and neck cancer
- infantile haemangioma
- primitive mesoderm
- tumour biology
- tumour markers
Aspects of this work were presented at the Australian and New Zealand Head and Neck Cancer Society, Sydney, Australia, 2–4 September 2010; the American Society of Plastic Surgeons' Meeting, Toronto, Canada, 1–5 October 2010; the 16th World Congress of the International Confederation for Plastic, Reconstructive and Aesthetic Surgery, Vancouver, Canada, 21–27 May 2011; and the 9th Annual Meeting of the International Society for Stem Cell Research, Toronto, Canada, 15–18 June 2011. This paper was awarded the prize for the best basic science presentation at the New Zealand Association of Plastic Surgeons' Annual Scientific Meeting, Auckland, New Zealand, 27–28 November 2011.
Funding This work was supported by grants from the Wellington Regional Plastic Surgery Unit Research and Education Trust, the Wellington Medical Research Foundation, the Surgical Research Trust, Pub Charities and the Cancer Society of New Zealand. AV was supported in part by the Cancer Society of New Zealand. TI is supported by the Royal Australasian College of Surgeons' foundation for surgery scholarship. None of these funders was involved in the research and its publication or for the publication.
Competing interests None.
Ethics approval All tissues used in this study were collected from patients according to a protocol approved by the Wellington Regional Ethics Committee. All SCID/NOD mice experiments were performed according to a protocol approved by the Victoria University of Wellington Animal Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.