Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

doi:10.1038/ncomms3497

Cited by 162 publications

(116 citation statements)

References 51 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…Thus, bioengineered salivary and lacrimal gland germs could be reconstituted by the organ germ method. 58,59 We confirmed that the bioengineered salivary and lacrimal glands could develop into mature glands though their transplantation into an adult mouse (Fig. 5B).…”

Section: Functional Salivary Gland and Lacrimal Gland Regenerationsupporting

confidence: 86%

Development and Prospects of Organ Replacement Regenerative Therapy

Hirayama

Oshima

Tsuji

2013

Cornea

Self Cite

View full text Add to dashboard Cite

Current approaches for the development of regenerative therapies have been influenced by our understanding of embryonic development, stem cell biology, and tissue engineering technology. The ultimate goal of regenerative therapy is to develop fully functioning bioengineered organs to replace lost or damaged organs that result from disease, injury, or aging. Almost all organs including ectodermal organs, such as teeth, hair, salivary glands, and lacrimal glands, arise from organ germs induced by reciprocal epithelial-mesenchymal interactions in the developing embryo. A novel concept to generate a bioengineered organ is to recreate organogenesis and thereby develop fully functioning bioengineered organs from the resulting bioengineered organ germ generated via 3-dimensional cell manipulation using immature stem cells in vitro. We have previously developed a bioengineering method for forming a 3-dimensional organ germ in the early developmental stages, termed the "bioengineered organ germ method." Recently, we reported fully functioning bioengineered tooth replacements after transplantation of a bioengineered tooth germ or a mature tooth unit comprising the bioengineered tooth and periodontal tissues. This concept could be adopted to generate not only teeth but also bioengineered hair follicles, salivary glands, and lacrimal glands. These studies emphasize the potential for bioengineered organ replacement in future regenerative therapies. In this review, we will summarize the strategies and the recent progress of research and development for the establishment of organ replacement regenerative therapies.

show abstract

Section: Functional Salivary Gland and Lacrimal Gland Regenerationsupporting

confidence: 86%

Development and Prospects of Organ Replacement Regenerative Therapy

Hirayama

Oshima

Tsuji

2013

Cornea

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent progress has been made in the development of strategies for regeneration and engineering of a variety of tissues, including skin (79,92), corneal epithelium (43), cartilage (85), bone (10,11), bladder (77), and lacrimal (48) and salivary glands (83). Determining the capacity of dispersed cells or tissue fragments to reassemble into native structures and the underlying mechanisms involved should provide novel insights to improve tissue regeneration approaches.…”

Section: Discussionmentioning

confidence: 99%

P2Y₂ nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells

El-Sayed

Camden

Woods

et al. 2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

El-Sayed FG, Camden JM, Woods LT, Khalafalla MG, Petris MJ, Erb L, Weisman GA. P2Y2 nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells. Am J Physiol Cell Physiol 307: C83-C96, 2014. First published April 24, 2014 doi:10.1152/ajpcell.00380.2013.-Hyposalivation resulting from salivary gland dysfunction leads to poor oral health and greatly reduces the quality of life of patients. Current treatments for hyposalivation are limited. However, regenerative medicine to replace dysfunctional salivary glands represents a revolutionary approach. The ability of dispersed salivary epithelial cells or salivary gland-derived progenitor cells to self-organize into acinarlike spheres or branching structures that mimic the native tissue holds promise for cell-based reconstitution of a functional salivary gland. However, the mechanisms involved in salivary epithelial cell aggregation and tissue reconstitution are not fully understood. This study investigated the role of the P2Y2 nucleotide receptor (P2Y2R), a G protein-coupled receptor that is upregulated following salivary gland damage and disease, in salivary gland reconstitution. In vitro results with the rat parotid acinar Par-C10 cell line indicate that P2Y2R activation with the selective agonist UTP enhances the self-organization of dispersed salivary epithelial cells into acinar-like spheres.Other results indicate that the P2Y2R-mediated response is dependent on epidermal growth factor receptor activation via the metalloproteases ADAM10/ADAM17 or the ␣5␤1 integrin/Cdc42 signaling pathway, which leads to activation of the MAPKs JNK and ERK1/2. Ex vivo data using primary submandibular gland cells from wild-type and P2Y2R

show abstract

“…(B) Then, submandibular gland (3) was noted at just inferolateral side of the ear. W e observed that the lacrimal gland (1) and parotid gland (2) were in front of the submandibular gland (3). The lacrimal and parotid glands were very close to each other.…”

mentioning

confidence: 84%

Transmission Electron Microscopic Findings of Lacrimal Gland Acinar Cells Induced byIn VivoDry Eye

Seo

Yeo

Noh

et al. 2014

J Korean Ophthalmol Soc

View full text Add to dashboard Cite

Purpose: To determine the change in lacrimal gland (LG) acinar cells induced by in vivo dry eye (DE).Methods: Six to 8-week-old (C57BL/6) mice were placed in a controlled environment chamber at <20% humidity for 2 weeks, and a control group was bred in a normal environment. After these 2 weeks of dry eye (DE) induction, the mice were sacrificed and their LGs were collected. Lacrimal gland acinar cell organelle structures were observed with Transmission Electron Microscopy (TEM). TEM images were analyzed using the Image J program. Results: The size of the LGs of DE-induced mice decreased compared to those of normal mice. Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) staining was negative in DE-induced LGs. Under the TEM, the endoplasmic reticulum (ER) lumen was dilated and the lumen density increased in DE-induced mice. Additionally, cell organelles were surrounded by elongated ER lumens. The mitochondrial structure was destroyed and the number of vacuoles increased in the LGs of DE-induced mice. Conclusions: Structural changes of the LG developed due to DE induction. This suggests that the detailed mechanisms of these changes were ER stress and autophagy. However, there were no definite signs of apoptosis in the acinar cells of the DE-induced LGs. These findings are regarded as an important clue of the pathogenesis of non-Sjogren-type dry eye.

show abstract

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

Cited by 162 publications

References 51 publications

Development and Prospects of Organ Replacement Regenerative Therapy

Development and Prospects of Organ Replacement Regenerative Therapy

P2Y₂ nucleotide receptor activation enhances the aggregation and self-organization of dispersed salivary epithelial cells

Transmission Electron Microscopic Findings of Lacrimal Gland Acinar Cells Induced byIn VivoDry Eye

Contact Info

Product

Resources

About