Lung regeneration: Implantation of fetal rat lung fragments into adult rat lung parenchyma

Kenzaki, Koichiro; Shoji, Shuichi; Kondo, Kazuya; Yoshida, Misao; Kawakami, Yukikiyo; Takehisa, Masatsugu; Takizawa, Hiromitsu; Miyoshi, Takanori; Bando, Yoshimi; Tangoku, Akira; Liu, Mingyao

doi:10.1016/j.jtcvs.2005.11.041

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…We previously described a novel intrapulmonary tracheal transplantation model of OB in rats, and demonstrated the connection of the grafts with the pulmonary circulation (10). Although obliterative fibrosis develops with similar kinetics to previously reported tracheal subcutaneous transplant models, the advantage of this model is that the graft is in the pulmonary milieu, which may have a significant relevance to the accommodation of implanted lung tissue (11). The pulmonary milieu could also be important for airway remodeling.…”

Section: Introductionmentioning

confidence: 62%

Allograft Airway Fibrosis in the Pulmonary Milieu: A Disorder of Tissue Remodeling

Sato

Liu

Anraku

et al. 2008

American Journal of Transplantation

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Obliterative bronchiolitis (OB) is thought to be a form of chronic allograft rejection. However, immunosuppressive therapy is not effective once fibrosis has developed. We hypothesize that disordered tissue remodeling is a mechanism for the pathogenesis of OB. We examined allograft airway fibrosis in an intrapulmonary tracheal transplant model of OB. Allograft airways were completely obliterated at day 21 by fibrotic tissue; however, tissue remodeling continued thereafter, as demonstrated by the change of collagen deposition density, shift from type I to type III collagen, shift from fibroblasts to myofibroblasts and shift of expression profiles and activities of matrix metalloproteinases (MMPs). We then used a broad-spectrum MMP inhibitor, SC080, to attempt to manipulate tissue remodeling. Administration of the MMP inhibitor from day 0 to day 28 reduced airway obliteration, without inhibiting T-cell activation. MMP inhibition from day 14 to day 28 showed similar effects on airway obliteration. MMP inhibition from day 21 to day 35 did not reverse the airway obliteration, but significantly reduced the collagen deposition, type III collagen and myofibroblasts in the lumen. We conclude that tissue remodeling plays a critical role in the development and maintenance of fibrosis after transplantation.

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Section: Introductionmentioning

confidence: 62%

Allograft Airway Fibrosis in the Pulmonary Milieu: A Disorder of Tissue Remodeling

Sato

Liu

Anraku

et al. 2008

American Journal of Transplantation

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“…Histological examination was performed as described above. This method reliably reveals vascular connections between the graft and the vasculature of the lung (7,16). Black ink particles were identified in blood vessels within the sponge.…”

Section: Allmentioning

confidence: 99%

Cell-based tissue engineering for lung regeneration

Andrade¹,

Wong²,

Waddell³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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113

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Emphysema is a chronic lung disease characterized by alveolar enlargement and tissue loss. Tissue engineering represents an attractive potential for regeneration of several organ systems. The complex three-dimensional architectural structure of lung parenchyma requiring connections of alveolar units to airways and the pulmonary circulation makes this strategy less optimistic. In the present study, we used Gelfoam sponge as a scaffold material, supplemented with fetal rat lung cells as progenitors, to explore the potential application of cell-based tissue engineering for lung regeneration in adult rats. After injection into lung parenchyma, the sponge showed porous structures similar to alveolar units. It did not induce severe local inflammatory response. Fetal lung cells in the sponge were able to survive in the adult lung for at least 35 days, determined by CMTMR [5-(and-6)-{[(4-chloromethyl)benzoyl]amino}tetramethylrhodamine] labeling. Proliferation of cells within the sponge was demonstrated in vivo by bromodeoxyuridine (BrdU) labeling. Cells formed “alveolar-like structures” at the border between the sponge and the surrounding lung tissue with positive immunohistochemical staining for epithelial and endothelial cells. Neovascularization of the sponge was demonstrated with India ink perfusion. The sponge degraded after several months. This study suggests that cell-based tissue engineering possesses the potential to regenerate alveolar-like structures, an important step towards our ultimate goal of lung regeneration.

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“…However, lung fragments obtained from adult rats did not expand after implantation. 61 These observations suggest that mechanical forces and premature lung cells and/or growth factors produced from premature cells are key elements for lung regrowth.…”

Section: Growth Factors Hormones and Other Factors In Compensatory mentioning

confidence: 97%

Molecular basis of lung tissue regeneration

Kubo

2011

Gen Thorac Cardiovasc Surg

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Recent advances have expanded our understanding of lung endogenous stem cells, and this knowledge provides us with new ideas for future regenerative therapy for lung diseases. In studies using animal models for lung regeneration, compensatory lung growth, and lung repair, promising reagents for lung regeneration have been discovered. Stem or progenitor cells are needed for alveolar regeneration, lung growth, and lung repair after injury. Endogenous progenitor cells mainly participate in alveologenesis. However, human lung endogenous progenitor cells have not yet been clearly defined. Recently discovered human alveolar epithelial progenitor cells may give us a new perspective for understanding the pathogenesis of lung diseases. In parallel with such basic research, projects geared toward clinical application are proceeding. Cell therapy using mesenchymal stem cells to treat acute lung injury is one of the promising areas for this research. The creation of bioartificial lungs, which are based on decellularized lungs, is another interesting approach for future clinical applications. Although lungs are the most challenging organ for regenerative medicine, our cumulative knowledge of lung regeneration and of endogenous progenitor cells makes clear the possibilities and limitations of regenerative medicine for lung diseases.

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Lung regeneration: Implantation of fetal rat lung fragments into adult rat lung parenchyma

Abstract: Fetal lung tissue might be an option for further investigation into lung regeneration.

Cited by 15 publications

References 27 publications

Allograft Airway Fibrosis in the Pulmonary Milieu: A Disorder of Tissue Remodeling

Allograft Airway Fibrosis in the Pulmonary Milieu: A Disorder of Tissue Remodeling

Cell-based tissue engineering for lung regeneration

Molecular basis of lung tissue regeneration

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