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Salisphere derived c-Kit(+) cell transplantation restores tissue homeostasis in irradiated salivary gland

Nanduri, L. S. Y., Lombaert, I. M. A., van der Zwaag, M., Faber, H., Brunsting, J. F., van Os, R. P. & Coppes, R. P., Sep-2013, In : Radiotherapy and Oncology. 108, 3, p. 458-463 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

Introduction: During radiotherapy salivary glands of head and neck cancer patients are unavoidably co-irradiated, potentially resulting in life-long impairment. Recently we showed that transplantation of salisphere-derived c-Kit expressing cells can functionally regenerate irradiated salivary glands. This study aims to select a more potent subpopulation of c-Kit(+) cells, co-expressing stem cell markers and to investigate whether long-term tissue homeostasis is restored after stem cell transplantation.

Methods and results: Salisphere derived c-Kit(+) cells that co-expressed CD24 and/or CD49f markers, were intra-glandularly injected into 15 Gy irradiated submandibular glands of mice. Particularly, c-Kit(+)/CD24(+)/CD49f(+) cell transplanted mice improved saliva production (54.59 +/- 11.1%) versus the irradiated control group (21.5 +/- 8.7%). Increase in expression of cells with differentiated duct cell markers like, cytokeratins (CK8, 18,7 and 14) indicated functional recovery of this compartment. Moreover, ductal stem cell marker expression like c-Kit, CD133, CD24 and CD49f reappeared after transplantation indicating long-term functional maintenance potential of the gland. Furthermore, a normalization of vascularization as indicated by 0331 expression and reduction of fibrosis was observed, indicative of normalization of the microenvironment.

Conclusions: Our results show that stem cell transplantation not only rescues hypo-salivation, but also restores tissue homeostasis of the irradiated gland, necessary for long-term maintenance of adult tissue. (C) 2013 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 108 (2013) 458-463

Original languageEnglish
Pages (from-to)458-463
Number of pages6
JournalRadiotherapy and Oncology
Volume108
Issue number3
Publication statusPublished - Sep-2013

    Keywords

  • c-Kit, Regeneration, Tissue homeostasis, Salivary gland, Stem cell, PATIENT-RATED XEROSTOMIA, ENDOTHELIAL-CELLS, NECK-CANCER, STICKY SALIVA, CLINICAL FACTORS, NTCP MODELS, HEAD, RADIOTHERAPY, ORGANOGENESIS, REGENERATION

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