scholarly journals Development of novel apoptosis-assisted lung tissue decellularization methods

2021 ◽  
Author(s):  
Young Hye Song ◽  
Mark Maynes ◽  
Nora Hlavac ◽  
Daniel Visosevic ◽  
Kaitlyn Daramola ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Lung Tissue ◽  
Disease Modeling

Decellularized tissues hold great potential for both regenerative medicine and disease modeling applications. The acellular extracellular matrix (ECM)-enriched scaffolds can be recellularized with patient-derived cells prior to transplantation, or digested...

scholarly journals Development of novel apoptosis-assisted lung tissue decellularization methods

2020 ◽  
Author(s):  
Young Hye Song ◽  
Mark A Maynes ◽  
Nora Hlavac ◽  
Daniel Visosevic ◽  
Kaitlyn O Daramola ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Lung Tissue ◽  
Disease Modeling ◽  
Complex Geometry ◽  
3D Cell Culture ◽  
Lung Epithelial Cells ◽  
Ecm Proteins ◽  
Effective Removal ◽  
Cellular Components

AbstractDecellularized tissues hold great potential for both regenerative medicine and disease modeling applications. The acellular extracellular matrix (ECM)-enriched scaffolds can be recellularized with patient-derived cells prior to transplantation, or digested to create thermally-gelling hydrogels for 3D cell culture. Current methods of decellularization clear cellular components using detergents, which can result in loss of ECM proteins and tissue architectural integrity. Recently, an alternative approach utilizing apoptosis to decellularize excised murine sciatic nerves resulted in superior ECM preservation, cell removal, and immune tolerance in vivo. However, this apoptosis-assisted decellularization approach has not been optimized for other tissues with a more complex geometry, such as lungs. To this end, we developed an apoptosis-assisted lung tissue decellularization method using a combination of camptothecin and sulfobetaine-10 (SB-10) to induce apoptosis and facilitate gentle and effective removal of cell debris, respectively. Importantly, combination of the two agents resulted in superior cell removal and ECM preservation compared to either of the treatments alone, presumably because of pulmonary surfactants. In addition, our method was superior in cell removal compared to a previously established detergent-based decellularization protocol. Furthermore, thermally-gelling lung ECM proteins supported high viability of rat lung epithelial cells for up to 2 weeks in culture. This work demonstrates that apoptosis-based lung tissue decellularization is a superior technique that warrants further utilization for both regenerative medicine and disease modeling applications.

scholarly journals iPSC technology-based regenerative medicine for kidney diseases

2021 ◽  
Author(s):  
Kenji Osafune
Keyword(s):  
Regenerative Medicine ◽  
Cell Therapy ◽  
Kidney Development ◽  
Disease Modeling ◽  
Kidney Diseases ◽  
Collecting Duct ◽  
Current Status ◽  
Renal Tubules ◽  
Discovery Research ◽  
Drug Discovery Research

AbstractWith few curative treatments for kidney diseases, increasing attention has been paid to regenerative medicine as a new therapeutic option. Recent progress in kidney regeneration using human-induced pluripotent stem cells (hiPSCs) is noteworthy. Based on the knowledge of kidney development, the directed differentiation of hiPSCs into two embryonic kidney progenitors, nephron progenitor cells (NPCs) and ureteric bud (UB), has been established, enabling the generation of nephron and collecting duct organoids. Furthermore, human kidney tissues can be generated from these hiPSC-derived progenitors, in which NPC-derived glomeruli and renal tubules and UB-derived collecting ducts are interconnected. The induced kidney tissues are further vascularized when transplanted into immunodeficient mice. In addition to the kidney reconstruction for use in transplantation, it has been demonstrated that cell therapy using hiPSC-derived NPCs ameliorates acute kidney injury (AKI) in mice. Disease modeling and drug discovery research using disease-specific hiPSCs has also been vigorously conducted for intractable kidney disorders, such as autosomal dominant polycystic kidney disease (ADPKD). In an attempt to address the complications associated with kidney diseases, hiPSC-derived erythropoietin (EPO)-producing cells were successfully generated to discover drugs and develop cell therapy for renal anemia. This review summarizes the current status and future perspectives of developmental biology of kidney and iPSC technology-based regenerative medicine for kidney diseases.

scholarly journals Special Issue: Application of Extracellular Matrix in Regenerative Medicine

2021 ◽  
Vol 11 (7) ◽  
pp. 3262
Author(s):  
Neill J. Turner
Keyword(s):  
Extracellular Matrix ◽  
Regenerative Medicine ◽  
Wound Repair ◽  
Three Dimensional ◽  
Dynamic Structure ◽  
Scaffold Material ◽  
Special Issue ◽  
Organ Regeneration ◽  
Scaffold Materials ◽  
The Many

The present Special Issue comprises a collection of articles addressing the many ways in which extracellular matrix (ECM), or its components parts, can be used in regenerative medicine applications. ECM is a dynamic structure, composed of a three-dimensional architecture of fibrous proteins, proteoglycans, and glycosaminoglycans, synthesized by the resident cells. Consequently, ECM can be considered as nature’s ideal biologic scaffold material. The articles in this Special Issue cover a range of topics from the use of ECM components to manufacture scaffold materials, understanding how changes in ECM composition can lead to the development of disease, and how decellularization techniques can be used to develop tissue-derived ECM scaffolds for whole organ regeneration and wound repair. This editorial briefly summarizes the most interesting aspects of these articles.

scholarly journals Evolution of Diploid Progenitor Lung Cell Applications: From Optimized Biotechnological Substrates to Potential Active Pharmaceutical Ingredients in Respiratory Tract Regenerative Medicine

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2526
Author(s):  
Alexis Laurent ◽  
Philippe Abdel-Sayed ◽  
Nathalie Hirt-Burri ◽  
Corinne Scaletta ◽  
Murielle Michetti ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Respiratory Tract ◽  
Lung Tissue ◽  
Cell Types ◽  
Active Pharmaceutical Ingredients ◽  
Vaccine Production ◽  
Diploid Progenitor ◽  
Pharmaceutical Ingredients ◽  
The 1960S ◽  
Pharmacopoeial Requirements

The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration.

Tenascin in rat lung development: in situ localization and cellular sources

1995 ◽  
Vol 269 (4) ◽  
pp. L482-L491 ◽  
Author(s):  
Y. Zhao ◽  
S. L. Young
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Epithelial Cells ◽  
Lung Tissue ◽  
Lung Development ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Alveolar Epithelial

Tenascin (TN) is a hexameric extracellular matrix glycoprotein that may play an important role during lung development. TN protein is temporally and spatially restricted during lung organogenesis. The temporo-spatial and cellular expression of TN mRNA in lung remains unclear. Localization of message expression of TN in rat lung tissue was first investigated by using in situ hybridization performed with an antisense RNA probe. TN mRNA was present primarily within the mesenchyme of day 16 gestational age fetal rat lung tissue, whereas immunoreactive TN protein was found along the basement membrane. In postnatal day 3 rat lung tissue, TN mRNA was detected along alveolar septal walls and was concentrated at secondary septal tips. Expression of TN message was consistent with localization of immunoreactive TN protein. Accumulation of TN mRNA in alveolar septal tips suggests that mesenchyme may be the major source of TN mRNA. To investigate the cellular source of TN in rat lung, we studied the expression of TN in cultured rat lung fibroblasts, endothelial cells, and alveolar epithelial cells. Two TN isoforms having molecular mass of 230 and 180 kDa were in conditioned medium and in cellular extracts of lung fibroblasts and endothelial cells. TN was secreted and deposited in the extracellular matrix closely associated with the surface of lung fibroblasts and endothelial cells. Lung alveolar epithelial cells showed undetectable or barely detectable amounts of TN. These studies demonstrated that TN isoforms are expressed not only by lung fibroblasts but also by lung endothelial cells. The unique spatial localization of TN mRNA during lung development and expression of TN by different lung cell types suggested TN may be involved in matrix organization and cell-cell interactions during lung development.

scholarly journals Genome editing in large animals: current status and future prospects

2019 ◽  
Vol 6 (3) ◽  
pp. 402-420 ◽  
Author(s):  
Jianguo Zhao ◽  
Liangxue Lai ◽  
Weizhi Ji ◽  
Qi Zhou
Keyword(s):  
Regenerative Medicine ◽  
Genome Editing ◽  
Biomedical Research ◽  
Human Disease ◽  
Gene Editing ◽  
Disease Modeling ◽  
Current Status ◽  
Future Prospects ◽  
Recent Advances ◽  
Large Animals

AbstractLarge animals (non-human primates, livestock and dogs) are playing important roles in biomedical research, and large livestock animals serve as important sources of meat and milk. The recently developed programmable DNA nucleases have revolutionized the generation of gene-modified large animals that are used for biological and biomedical research. In this review, we briefly introduce the recent advances in nuclease-meditated gene editing tools, and we outline these editing tools’ applications in human disease modeling, regenerative medicine and agriculture. Additionally, we provide perspectives regarding the challenges and prospects of the new genome editing technology.

scholarly journals iPSC-Derived Liver Organoids: A Journey from Drug Screening, to Disease Modeling, Arriving to Regenerative Medicine

2020 ◽  
Vol 21 (17) ◽  
pp. 6215
Author(s):  
Cristina Olgasi ◽  
Alessia Cucci ◽  
Antonia Follenzi
Keyword(s):  
Regenerative Medicine ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Cell Types ◽  
High Rate ◽  
Limiting Factor ◽  
Congenital Diseases ◽  
Induced Pluripotent ◽  
Liver Organoids ◽  
Bioartificial Livers

Liver transplantation is the most common treatment for patients suffering from liver failure that is caused by congenital diseases, infectious agents, and environmental factors. Despite a high rate of patient survival following transplantation, organ availability remains the key limiting factor. As such, research has focused on the transplantation of different cell types that are capable of repopulating and restoring liver function. The best cellular mix capable of engrafting and proliferating over the long-term, as well as the optimal immunosuppression regimens, remain to be clearly well-defined. Hence, alternative strategies in the field of regenerative medicine have been explored. Since the discovery of induced pluripotent stem cells (iPSC) that have the potential of differentiating into a broad spectrum of cell types, many studies have reported the achievement of iPSCs differentiation into liver cells, such as hepatocytes, cholangiocytes, endothelial cells, and Kupffer cells. In parallel, an increasing interest in the study of self-assemble or matrix-guided three-dimensional (3D) organoids have paved the way for functional bioartificial livers. In this review, we will focus on the recent breakthroughs in the development of iPSCs-based liver organoids and the major drawbacks and challenges that need to be overcome for the development of future applications.

scholarly journals Influence of obesity on remodeling of lung tissue and organization of extracellular matrix after blunt thorax trauma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Pengfei Xu ◽  
Fabian Gärtner ◽  
Adrian Gihring ◽  
Congxing Liu ◽  
Timo Burster ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Protein Level ◽  
Morphological Changes ◽  
Matrix Composition ◽  
Collagen Deposition ◽  
Obese Mice ◽  
Time Points ◽  
Extracellular Matrix Components ◽  
Thorax Trauma

Abstract Background Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. Methods This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). Results Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. Conclusions In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.

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