Similar ex vivo expansion and post-irradiation regenerative potential of juvenile and aged salivary gland stem cells

Maimets, Martti; Bron, Reinier; Haan, Gerald de; Os, Ronald van; Coppes, Robert P.

doi:10.1016/j.radonc.2015.06.022

Cited by 27 publications

(19 citation statements)

References 21 publications

(39 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acknowledging caveats of the different mouse models used, these data suggest firstly that human salisphere cells hold great therapeutic promise for rescue of hyposalivation and secondly that purification of a potent stem cell subset from the heterogeneous salisphere population may enhance hyposalivation recovery. It should be noted, however, that the frequency of c‐Kit + cells in primary cultures is extremely low, and appears even to decrease with age, in agreement with our previous studies showing decrease in overall primary salisphere yield with age . These data suggest that other, more abundant stem cell marker proteins may be more suitable (Fig.…”

Section: Resultssupporting

confidence: 90%

“…E). Further analysis demonstrated a moderate upregulation of soluble factors associated with SG branching and development (transforming growth factor (TGF)b1, TGFb3, bone morphogenetic protein1) , SG stem cell maintenance (insulin growth factor, EGF) (Supplementary Information Fig. S9B), and SG functionality (α‐amylase, AQP‐1, DCPP2, DCPP3, PSP) (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

et al. 2016

Self Cite

View full text Add to dashboard Cite

Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model. Indeed, transplanted human salisphere-derived cells restored saliva production and greatly improved the regenerative potential of irradiated SGs. Further selection for c-Kit expression enriched for cells with enhanced regenerative potencies. Interestingly, interaction of transplanted cells with the recipient SG may also be involved in functional recovery. Thus, we show for the first time that salispheres cultured from human SGs contain stem/progenitor cells capable of self-renewal and differentiation and rescue of saliva production. Our study underpins the therapeutic promise of salisphere cell therapy for the treatment of xerostomia. STEM CELLS 2016;34:640-652 SIGNIFICANCE STATEMENTThis study describes the isolation, cultivation, and clinical potential of human salivary gland stem cells to treat radiation-induced xerostomia. We show the ability of human salivary gland derived cells to self-renew and differentiate in vitro and functionally restore irradiated salivary glands after xenotransplantation. The study is the final step toward clinical application.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following the discovery that single stem cells form spheres or aggregates through proliferation and differentiation, “sphere” cultures have been widely used for culture of intestine, liver, mammary gland, and neural tissue, and have also been adapted for salivary glands (Cao et al, 2011; Feng et al, 2009; Ishiguro et al, 2017; Lathia, Mack, Mulkearns-Hubert, Valentim, & Rich, 2015; Lombaert, Brunsting, Wierenga, Faber, et al, 2008; Maimets, Bron, de Haan, van Os, & Coppes, 2015; Manuel Iglesias et al, 2013; Min, Lee, Bak, & Kim, 2015; Nanduri et al, 2011; Reynolds & Weiss, 1992; Shubin, Felong, Graunke, Ovitt, & Benoit, 2015; Smart et al, 2013). Using rigorous techniques, sphere culture enables isolation and expansion of clonogenic stem/progenitor cell populations with growth only through proliferation (Chen et al, 2012; Reynolds & Weiss, 1992).…”

Section: Introductionmentioning

confidence: 99%

Salivary gland cell aggregates are derived from self-organization of acinar lineage cells

Varghese

Hansen

Sharipol

et al. 2019

Archives of Oral Biology

View full text Add to dashboard Cite

Objective: The objective of this study was to characterize the mechanism by which salivary gland cells (SGC) aggregate in vitro. Design: Timelapse microscopy was utilized to analyze the process of salivary gland aggregate formation using both primary murine and human salivary gland cells. The role of cell density, proliferation, extracellular calcium, and secretory acinar cells in aggregate formation was investigated. Finally, the ability of cells isolated from irradiated glands to form aggregates was also evaluated. Results: Salivary gland cell self-organization rather than proliferation was the predominant mechanism of aggregate formation in both primary mouse and human salivary gland cultures (SGC). Aggregation was found to require extracellular calcium while acinar lineage cells account for ~80% of the total aggregate cell population. Finally, aggregation was not impaired by irradiation. Conclusions: The data reveal that aggregation occurs as a result of heterogeneous salivary gland cell self-organization rather than from stem cell proliferation and differentiation, contradicting previous dogma. These results suggest a re-evaluation of aggregate formation as a criterion defining salivary gland stem cells.

show abstract

“…For effective investigations, it is important to perform consistent, clean dissections of the major salivary glands. Clean and efficient gland isolation is critical for cultures derived from primary cells that are mechanically and enzymatically dissociated from the major salivary glands 30,31 , and for histologic and immunohistochemical preparations. Moreover, when staining for secreted proteins in gland tissue sections, it is critical to consider and control for the likely depletion of these products following stimulated saliva collection.…”

Section: Discussionmentioning

confidence: 99%

Murine Salivary Functional Assessment via Pilocarpine Stimulation Following Fractionated Radiation

Varghese

Schmale

Hansen

et al. 2018

JoVE

View full text Add to dashboard Cite

SHORT ABSTRACT We present a detailed approach to performing saliva collection, including murine tracheostomy and the isolation of three major salivary glands. LONG ABSTRACT Hyposalivation is commonly observed in the autoimmune reaction of Sjögren’s syndrome or following radiation injury to the major salivary glands. In these cases, questions remain regarding disease pathogenesis and effective interventions. An optimized technique that allows functional assessment of the salivary glands is invaluable for investigating exocrine gland biology, dysfunction, and therapeutics. Here, we present a step by step approach to performing pilocarpine stimulated saliva secretion, including tracheostomy and the dissection of the three major murine salivary glands. We also detail the appropriate murine head and neck anatomy accessed during these techniques. This approach is scalable, allowing for multiple mice to be processed simultaneously, thus improving the efficiency of the work flow. We aim to improve the reproducibility of these methods, each of which has further applications within the field. In addition to saliva collection, we discuss metrics for quantifying and normalizing functional capacity of these tissues. Representative data are included from submandibular glands with depressed salivary gland function 2 weeks following fractionated radiation (4 doses of 6.85 Gy).

show abstract

Similar ex vivo expansion and post-irradiation regenerative potential of juvenile and aged salivary gland stem cells

Abstract: Aged SGSCs although reduced in number are in vitro indistinguishable from young SGSCs and could potentially be used to ameliorate age- or treatment related salivary gland dysfunction.

Cited by 27 publications

References 21 publications

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

Human Salivary Gland Stem Cells Functionally Restore Radiation Damaged Salivary Glands

Salivary gland cell aggregates are derived from self-organization of acinar lineage cells

Murine Salivary Functional Assessment via Pilocarpine Stimulation Following Fractionated Radiation

Contact Info

Product

Resources

About