Tissue Engineering of Lung

a tissue engineering and lung technology, applied in the field of lung tissue engineering, can solve the problems of lung being difficult to engineer in the laboratory, affecting the quality of lung tissue, and wide range of problems,

Inactive Publication Date: 2012-03-15
YALE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0023]In one embodiment, the method comprises determining the effect of the test agent on cell number, area, volume, shape, morphology, marker expression or c

Problems solved by technology

Immunosuppression is necessary to prevent rejection of the transplanted organ, but can lead to a wide range of problems, including infection, malignancy, kidney impairment, cardiovascular problems, and neurologic disorders [Pietra et al., 2000, J Clin Invest 106:1003-10; Christie et al., 2009, J Heart Lung Transplant 28:1031-49].
However, lung is a difficult tissue to engineer in the laboratory.
Furthermore, pulmo

Method used

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Examples

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experimental examples

[0221]The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

example 1

Decellularization of Rat Lung and Morphological Characterization of Decellularized Scaffolds

[0222]A decellularized organ offers several advantages for use as a tissue engineering scaffold. In one aspect, the decellularized scaffold contains the appropriate 3-dimensional organization required for tissue function, including a vascular system and airway network in the case of lung. In addition, extracellular matrix (ECM) components are widely conserved across species, thus reducing the likelihood of a decellularized scaffold inducing an immune response upon xenogeneic implantation [Bernard et al., 1983, Biochemistry 1983; 22:5213-23]. In another aspect, native ECM offers the optimal substrate for cell attachment, spreading, growth and differentiation.

[0223]The goal of the decellularization process of the present invention is to remove cellular and nuclear material while retaining key aspects of and minimizing any damage to the ECM of the lung. The results presented herein demonstrate t...

example 2

Contribution of Extracellular Matrix Components to the Mechanical Integrity of Decellularized Lung Tissue

[0269]The following experiments were designed to evaluate the composition of the decellularized scaffolds in more detail with a focus on the mechanical properties of the scaffolds. Without wishing to be bound by any particular theory, it is believed that that decellularized lung scaffolds retain salient mechanical features of native lung, due principally to contributions from collagen and elastin. The results presented herein demonstrate the utility of the decellularized lung tissue as a platform to study lung mechanics independent of cellular contributions.

[0270]The results presented herein demonstrate that collagen content is retained, elastin content is retained at ˜40% of native levels, while glycosaminoglycans are largely lost from the decellularized scaffolds.

[0271]The materials and methods employed in these experiments are now described.

Materials and Methods

[0272]Organ Har...

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Abstract

The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.

Description

BACKGROUND OF THE INVENTION[0001]Every year, 400,000 Americans die of lung disease. Of further concern, the death rate due to lung disease is increasing, while the death rates for the other major disease categories are decreasing (heart disease, cancer and stroke). For several lung diseases, including cystic fibrosis, emphysema / COPD, and idiopathic pulmonary fibrosis, lung transplantation remains the only definitive treatment. However, patient survival after lung transplant is only 50% at 5 years and 24% at 10 years [Mondrinos et al., 2008, Tissue Eng 14:361-8]. There is therefore great demand for the development of engineered lung tissue that could be used for transplantation. One advantage of engineered lung tissue is that the tissue can be grown using a patient's own cells, thereby avoiding the need for strong immunosuppression, as is required with current lung transplantation. Immunosuppression is necessary to prevent rejection of the transplanted organ, but can lead to a wide r...

Claims

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Application Information

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IPC IPC(8): A61K35/42A61P11/00C12Q1/68C12N5/071C12Q1/02
CPCA61K35/42C12N2533/90C12N5/0688A61P11/00A61P43/00
Inventor CALLE, ELIZABETHNIKLASON, LAURA E.PETERSON, THOMASGUI, LIQIONG
Owner YALE UNIV
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