The protective efficacy of basic fibroblast growth factor in radiation-induced salivary gland dysfunction in mice

Kojima, Tsuyoshi; Kanemaru, Shin‐ichi; Hirano, Shigeru; Tateya, Ichiro; Suehiro, Atsushi; Kitani, Yoshiharu; Kishimoto, Yo; Ohno, Satoshi; Nakamura, Tatsuo; Ito, Juichi

doi:10.1002/lary.21873

Cited by 33 publications

(23 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both injected and mobilized BM cells (such as with granulocyte-colony stimulating factor) were found effective in partially restoring function in irradiated-SGs. Injections or vector-mediated transfer of growth factors (such as FGF2, IGF, KGF or VEGF) without cell transplants were also reported partially effective in repairing irradiated-SGs [41], [42], [43], [44], [45]. Taken these studies together, the data suggest that BM cells, specific growth factors, or combining both approaches could be used to restore SG organ function.…”

Section: Discussionmentioning

confidence: 88%

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

et al. 2013

View full text Add to dashboard Cite

BackgroundThere are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated.MethodsTo test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as “BM Soup”) injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup’s donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation.Results BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold.Conclusion BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.

show abstract

Section: Discussionmentioning

confidence: 88%

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

et al. 2013

View full text Add to dashboard Cite

show abstract

“…2C). 19 Interestingly, SMG from the 39-year-old female patient (patient 4) displayed high levels of collagen deposition (although less than patient 3), which appears to be typical of early radiation stages 20 …”

Section: Gamma Irradiation Causes Collagen Deposition In Human Smgmentioning

confidence: 99%

Post-Irradiated Human Submandibular Glands Display High Collagen Deposition, Disorganized Cell Junctions, and an Increased Number of Adipocytes

Nam

Maruyama

Trump

et al. 2016

J Histochem Cytochem.

View full text Add to dashboard Cite

Salivary glands are vital for maintaining oral health. Head and neck radiation therapy is one of the most common causes of salivary gland hypofunction. Little is known about the structural changes that occur in salivary glands after radiation therapy. The aim of this study is to understand the structural changes that occur in post-irradiated human (submandibular gland [SMG]) as compared with untreated ones. We determined changes in epithelial polarity, presence of collagen deposition, and alteration in adipose tissue. We used formalin-fixed paraffin-embedded human SMG from two female subjects exposed to head and neck irradiation. We utilized hematoxylin and eosin staining and Masson’s Trichrome staining. The immunostained tissue sections were examined using confocal microscopy. The number and size of adipocytes per tissue section were calculated using ImageJ, Prism, and SPSS software. Post-irradiated human SMG displayed high collagen deposition, disorganized cell junctions, and an increased number of adipocytes as compared with non-irradiated controls. These findings are important to improve our understanding of the individual risk and variation in radiation-related salivary gland dysfunction.

show abstract

“…An increasing number of studies using bioactive factors for prevention or amelioration of irradiation-induced SG damage have been conducted [3–6]. Keratinocyte growth factor-1 (KGF-1, also known as FGF-7) stimulates the growth of epithelial cells and protects those cells from chemotherapy or radiotherapy-induced oral mucositis.…”

Section: Introductionmentioning

confidence: 99%

Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction

Choi

Shin

et al. 2017

Oncotarget

View full text Add to dashboard Cite

Irradiation can cause salivary gland hypofunction, with hyposalivation producing discomfort, health risks, and reducing function in daily life. Despite increasing translational research interest in radioprotection, there are no satisfactory treatments available. Keratinocyte growth factor-1 stimulates proliferation of salivary epithelial cells or salivary stem/progenitor cells. However, the exact mechanism of its radioprotection against radiation-induced salivary hypofunction is not fully elucidated. Our results reveal that the radioprotective effects of keratinocyte growth factor-1 involved alleviation of growth inhibition and anti-apoptotic cell death of human parotid epithelial cells. Furthermore, keratinocyte growth factor-1 protected human parotid epithelial cells through the phosphoinositide 3-kinase – protein kinase B (Akt) pathway and inhibition of p53-mediated apoptosis through activation of mouse double minute 2. Local delivery of keratinocyte growth factor-1 into the irradiated salivary glands could protect radiation-induced salivary cell damages, suppress p53-mediated apoptosis and prevent salivary hypofunction in vivo. This suggests that keratinocyte growth factor-1 is a promising candidate to prevent radiation-induced salivary hypofunction and raise rational development keratinocyte growth factor-1 local delivery system.

show abstract

The protective efficacy of basic fibroblast growth factor in radiation-induced salivary gland dysfunction in mice

Abstract: Our study indicates that bFGF prevents salivary gland dysfunction after irradiation. The protective benefits of bFGF may be attributed to the inhibition of radiation-induced apoptosis as well as the paracrine effect it has in these tissues.

Cited by 33 publications

References 22 publications

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

Paracrine Effects of Bone Marrow Soup Restore Organ Function, Regeneration, and Repair in Salivary Glands Damaged by Irradiation

Post-Irradiated Human Submandibular Glands Display High Collagen Deposition, Disorganized Cell Junctions, and an Increased Number of Adipocytes

Radioprotective effects of Keratinocyte Growth Factor-1 against irradiation-induced salivary gland hypofunction

Contact Info

Product

Resources

About