Isolation and Cultivation of Integrin α₆β₁–Expressing Salivary Gland Graft Cells: A Model for Use with an Artificial Salivary Gland

Abstract

Regeneration of the salivary glands' (SGs) normal function for patients with cancer of the head and neck treated with irradiation would be a major contribution to their quality of life. This could be accomplished by re-implantation of autologous SG cells into the residual irradiated tissue or by implantation of tissue-engineered artificial SGs. Both methods depend on the isolation of cells able to propagate and differentiate into SG epithelial cells. Recently, it has been shown that SG integrin alpha(6)beta(1)-expressing (SGIE) cells have stem cell capabilities, but these cells could be isolated only after duct ligation insult requiring surgical intervention. Because such an invasive procedure is not clinically acceptable for these patients, our aim in the present study was to explore the use of immuno-magnetic separation of untreated and short heat stress-conditioned rats as a less-insulting methodology for enhancement of these cells. Our results show that submandibular SGIE cells could be isolated and cultivated from untreated animals. However, short heat stress (HS) increased the number of isolated SGIE cells 4.7-fold and their proliferation and clonal capability 4.6-fold and 3 fold, respectively. We believe that SGIE graft cells may be suitable candidates for future tissue-engineered SGs that have been damaged by irradiation in patients with head and neck cancer.

Ascl3 marks adult progenitor cells of the mouse salivary gland

“…The relationship between the populations of putative progenitor cells so far identified in the salivary glands [1–5, 24, 25] is not yet clear. Ascl3+ progenitor cells are located in the ducts in vivo , as are the basal cell Krt5+ progenitors [4].…”

“…A number of progenitor cell populations have been identified in the salivary gland [1, 2, 4, 5, 24, 25]. In addition to Ascl3, c-Kit and Keratin 5 also mark progenitor cells [4, 5].…”

Single Cell Clones Purified from Human Parotid Glands Display Features of Multipotent Epitheliomesenchymal Stem Cells

“…showed that the CD24 + CD117 + Sca1 + subpopulation derived from mouse salispheres augments acinar function and restores saliva secretion17. Conversely, murine SG stem/progenitor cells isolated by adherent cell culture have been shown to express MSC markers (CD29, CD44, CD49f, and CD90), as well as c-Kit and Sca-1718192021.…”

Anatomy, Biogenesis and Regeneration of Salivary Glands

“…Further study of the Kit-expressing cells also showed that this cell population is located in the ducts of the adult SMG [44]. In addition, stem/progenitor cells of the ducts that were activated in response to injury were shown to express markers Sca1 and Kit [45,46], α6β1-integrin [47] or CD49f (α6-integrin) and Thy1 [48,49]. Furthermore, Ascl3, a transcription factor, also marks a stem/progenitor population that is localized in the salivary ducts [50].…”