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

Lalitha S. Y. Nanduri, Isabelle M. A. Lombaert, Marianne van der Zwaag, Hette Faber, Jeanette F. Brunsting, Ronald P. van Os, Robert P. Coppes*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

80 Citations (Scopus)

Abstract

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
DOIs
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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