Origin of acinar cell regeneration after atrophy of the rat parotid induced by duct obstruction

Takahashi, Shigeru; Schoch, Estelle; Walker, Neal I.

doi:10.1046/j.1365-2613.1998.710405.x

Cited by 73 publications

(98 citation statements)

References 15 publications

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“…Studies of salivary gland stem cells have reported c-Kit, Sca-1, and Musashi-1 as stem cell markers 17,[31][32][33][34][35] . There are also a number of reports mentioning that epithelial stem cells of the salivary gland duct are present in intercalated ducts 36,37) and that they are present in the duct-like structures of atrophied salivary glands 7,38) . In addition, differentiated cells are reported to participate in regeneration 38,39) .…”

Section: Discussionmentioning

confidence: 99%

“…There are also a number of reports mentioning that epithelial stem cells of the salivary gland duct are present in intercalated ducts 36,37) and that they are present in the duct-like structures of atrophied salivary glands 7,38) . In addition, differentiated cells are reported to participate in regeneration 38,39) . In the present study, we found PSCA in the intercalated ducts of normal submandibular glands and c-Kit in the duct-like structures of atrophied salivary glands.…”

Section: Discussionmentioning

confidence: 99%

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Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice

Akadomari

Tanaka

Mataga

2016

J. Hard Tissue Biology.

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Function degeneracy of the salivary gland leads to reduced protection against infection and reduced physiological function of the oral cavity, considerably diminishing the patient's quality of life. However, no method of treatment has yet been established to recover the secretory capacity of the salivary gland reduced by the degeneration or disappearance of the gland tissue. Ongoing salivary gland regeneration experiments using cell transplantation aim to introduce clinical regenerative treatment for the salivary gland. Because it is essential to understand the self-regenerative capacity that remains in the recipient's salivary gland, it is essential to search for optimal conditions for transplantation and establish a salivary gland atrophy model. In this context, we performed duct ligation of the submandibular gland in groups of mice for 7-, 14-, and 21-day ligation periods, compared immunohistochemical staining using acinar cell and stem cell markers, detected apoptosis using TUNEL staining, and analyzed gene expression using RT-PCR to search for the expression of factors related to regenerative capacity that remain in the atrophic salivary gland. All 3 periods of ligation led to remarkable atrophy/disappearance of acinar cells and the dominant presence of duct-like structures. These structures expressed stem cell markers most intensively after 14 days of ligation, and double immunostaining revealed the expressions of PSCA and c-Kit that coincided with them. AQP5 expression was detected in acinar cells and the apical membrane of the intercalated ducts in the normal submandibular gland and was also detected after 21 days of ligation in the remnant acinar cells and intercalated ducts. Conversely, the number of TUNELpositive apoptotic cells in the atrophic salivary gland was highest after 7 days of ligation. These results showed that the duct-like structures that exist after ligation expressed stem cell markers and AQP5, indicating the presence of a mechanism related to the regeneration of salivary gland tissue.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Regenerative Capacity of Atrophic Submandibular Gland by Duct Ligation in Mice

Akadomari

Tanaka

Mataga

2016

J. Hard Tissue Biology.

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“…The ductal tree plays an important role in modulating the composition of saliva, and in rodents, it is comprised of the intercalated ducts, the convoluted granular tubules, and the secretory and excretory ducts. Ductal cells have gained importance in salivary gland regeneration, since they were found to harbor putative progenitor stem cells (Takahashi et al, 1998;Man et al, 2001). Stem cells within the intercalated ducts can differentiate into amylase-producing acinar cells to aid recovery of gland function after radiation injury and after ductal ligation-induced gland atrophy (Lombaert et al, 2008;Cotroneo et al, 2010).…”

Section: Aav9-tlk1b Protects Against Ir-mediated Xerostomiamentioning

confidence: 99%

Recombinant AAV9-TLK1B Administration Ameliorates Fractionated Radiation-Induced Xerostomia

Shanmugam

Dayton²,

Palaniyandi³

et al. 2013

Human Gene Therapy

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Salivary glands are highly susceptible to radiation, and patients with head and neck cancer treated with radiotherapy invariably suffer from its distressing side effect, salivary hypofunction. The reduction in saliva disrupts oral functions, and significantly impairs oral health. Previously, we demonstrated that adenoviralmediated expression of Tousled-like kinase 1B (TLK1B) in rat submandibular glands preserves salivary function after single-dose ionizing radiation. To achieve long-term transgene expression for protection of salivary gland function against fractionated radiation, this study examines the usefulness of recombinant adeno-associated viral vector for TLK1B delivery. Lactated Ringers or AAV2/9 with either TLK1B or GFP expression cassette were retroductally delivered to rat submandibular salivary glands (10 11 vg/gland), and animals were exposed, or not, to 20 Gy in eight fractions of 2.5 Gy/day. AAV2/9 transduced predominantly the ductal cells, including the convoluted granular tubules of the submandibular glands. Transgene expression after virus delivery could be detected within 5 weeks, and stable gene expression was observed till the end of study. Pilocarpine-stimulated saliva output measured at 8 weeks after completion of radiation demonstrated >10-fold reduction in salivary flow in saline-and AAV2/9-GFP-treated animals compared with the respective nonirradiated groups (90.8% and 92.5% reduction in salivary flow, respectively). Importantly, there was no decrease in stimulated salivary output after irradiation in animals that were pretreated with AAV2/9-TLK1B (121.5% increase in salivary flow; p < 0.01). Salivary gland histology was better preserved after irradiation in TLK1B-treated group, though not significantly, compared with control groups. Single preemptive delivery of AAV2/9-TLK1B averts salivary dysfunction resulting from fractionated radiation. Although AAV2/9 transduces mostly the ductal cells of the gland, their protection against radiation assists in preserving submandibular gland function. AAV2/9-TLK1B treatment could prove beneficial in attenuating xerostomia in patients with head and neck cancer undergoing radiotherapy.

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“…19 The same method is applied in the case of the salivary gland regarding tissue injury and regeneration. 20 In the salivary gland, 1 week after ligation of the main excretory duct, almost all of the acinar cells disappeared as a result of apoptosis 21,22 and extensive proliferation of the duct epithelium occurred. 20 Reopening of the obstructed duct resulted in regeneration of normal gland tissues.…”

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confidence: 99%