3D Bioprinting Strategies, Challenges, and Opportunities to Model the Lung Tissue Microenvironment and Its Function

Human lungs are organs with an intricate hierarchical structure and complex composition; lungs also present heterogeneous mechanical properties that impose dynamic stress on different tissue components during the process of breathing. These physiological characteristics combined create a system that is challenging to model in vitro. Many efforts have been dedicated to develop reliable models that afford a better understanding of the structure of the lung and to study cell dynamics, disease evolution, and drug pharmacodynamics and pharmacokinetics in the lung. This review presents methodologies used to develop lung tissue models, highlighting their advantages and current limitations, focusing on 3D bioprinting as a promising set of technologies that can address current challenges. 3D bioprinting can be used to create 3D structures that are key to bridging the gap between current cell culture methods and living tissues. Thus, 3D bioprinting can produce lung tissue biomimetics that can be used to develop in vitro models and could eventually produce functional tissue for transplantation. Yet, printing functional synthetic tissues that recreate lung structure and function is still beyond the current capabilities of 3D bioprinting technology. Here, the current state of 3D bioprinting is described with a focus on key strategies that can be used to exploit the potential that this technology has to offer. Despite today’s limitations, results show that 3D bioprinting has unexplored potential that may be accessible by optimizing bioink composition and looking at the printing process through a holistic and creative lens.

Download Full-text

Development of Hydrogel Bioinks and 3D Bioprinting Techniques to Support Extended 3D Lung Tissue Culture In Vitro

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2552 ◽

2019 ◽

Author(s):

K.E. Bailey ◽

N.J. Darling ◽

D. Velu ◽

T.J. D'Ovidio ◽

M.L. Floren ◽

...

Keyword(s):

Tissue Culture ◽

Lung Tissue ◽

3D Bioprinting ◽

Culture In Vitro

Download Full-text

Constructing stem cell microenvironments using bioengineering approaches

Physiological Genomics ◽

10.1152/physiolgenomics.00099.2013 ◽

2013 ◽

Vol 45 (23) ◽

pp. 1123-1135 ◽

Cited By ~ 29

Author(s):

David A. Brafman

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cell Fate ◽

Disease Modeling ◽

Mechanical Stimuli ◽

Culture Methods ◽

Stem Cell Fate ◽

And Function

Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

Download Full-text

Building neuromuscular junctions in vitro

Development ◽

10.1242/dev.193920 ◽

2020 ◽

Vol 147 (22) ◽

pp. dev193920

Author(s):

Susie Barbeau ◽

Julie Tahraoui-Bories ◽

Claire Legay ◽

Cécile Martinat

Keyword(s):

Human Disease ◽

Molecular Mechanisms ◽

Neuromuscular Junctions ◽

Ex Vivo ◽

Culture Methods ◽

Recent Developments ◽

Chemical Synapses ◽

And Function

ABSTRACTThe neuromuscular junction (NMJ) has been the model of choice to understand the principles of communication at chemical synapses. Following groundbreaking experiments carried out over 60 years ago, many studies have focused on the molecular mechanisms underlying the development and physiology of these synapses. This Review summarizes the progress made to date towards obtaining faithful models of NMJs in vitro. We provide a historical approach discussing initial experiments investigating NMJ development and function from Xenopus to mice, the creation of chimeric co-cultures, in vivo approaches and co-culture methods from ex vivo and in vitro derived cells, as well as the most recent developments to generate human NMJs. We discuss the benefits of these techniques and the challenges to be addressed in the future for promoting our understanding of development and human disease.

Download Full-text

Harnessing Mesenchymal Stromal Cells for the Engineering of Human Hematopoietic Niches

Frontiers in Immunology ◽

10.3389/fimmu.2021.631279 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alice Pievani ◽

Roberto Savoldelli ◽

Juliane Poelchen ◽

Elisa Mattioli ◽

Giorgio Anselmi ◽

...

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Drug Testing ◽

Artificial Immune ◽

Hematopoietic Organs ◽

Challenges And Opportunities ◽

Health And Disease ◽

And Function

Tissue engineering opens multiple opportunities in regenerative medicine, drug testing, and modeling of the hematopoiesis in health and disease. Recapitulating the organization of physiological microenvironments supporting leukocyte development is essential to model faithfully the development of immune cells. Hematopoietic organs are shaped by spatially organized niches defined by multiple cellular contributions. A shared feature of immune niches is the presence of mesenchymal stromal cells endowed with unique roles in organizing niche development, maintenance, and function. Here, we review challenges and opportunities in harnessing stromal cells for the engineering of artificial immune niches and hematopoietic organoids recapitulating leukocyte ontogeny both in vitro and in vivo.

Download Full-text

Molecular architecture and functions of the neuronal cytoskeleton

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157541 ◽

1990 ◽

Vol 48 (3) ◽

pp. 2-3

Author(s):

Nobutaka Hirokawa

Keyword(s):

Major Elements ◽

Molecular Structures ◽

Organelle Transport ◽

Molecular Architecture ◽

Neuronal Morphogenesis ◽

Microtubule Associated Proteins ◽

Associated Proteins ◽

And Function ◽

Small Clusters

In this symposium I will present our studies about the molecular architecture and function of the cytomatrix of the nerve cells. The nerve cell is a highly polarized cell composed of highly branched dendrites, cell body, and a single long axon along the direction of the impulse propagation. Each part of the neuron takes characteristic shapes for which the cytoskeleton provides the framework. The neuronal cytoskeletons play important roles on neuronal morphogenesis, organelle transport and the synaptic transmission. In the axon neurofilaments (NF) form dense arrays, while microtubules (MT) are arranged as small clusters among the NFs. On the other hand, MTs are distributed uniformly, whereas NFs tend to run solitarily or form small fascicles in the dendrites Quick freeze deep etch electron microscopy revealed various kinds of strands among MTs, NFs and membranous organelles (MO). These structures form major elements of the cytomatrix in the neuron. To investigate molecular nature and function of these filaments first we studied molecular structures of microtubule associated proteins (MAP1A, MAP1B, MAP2, MAP2C and tau), and microtubules reconstituted from MAPs and tubulin in vitro. These MAPs were all fibrous molecules with different length and formed arm like projections from the microtubule surface.

Download Full-text

Decision letter for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v2/decision1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

Download Full-text

Review for "Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro"

10.1002/eji.201948240/v1/review1 ◽

2019 ◽

Keyword(s):

B Cell ◽

Suppressor Cells ◽

Cell Phenotype ◽

Myeloid Derived Suppressor Cells ◽

And Function

Download Full-text

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614605 ◽

1999 ◽

Vol 81 (06) ◽

pp. 951-956 ◽

Cited By ~ 59

Author(s):

J. Corral ◽

R. González-Conejero ◽

J. Rivera ◽

F. Ortuño ◽

P. Aparicio ◽

...

Keyword(s):

Venous Thrombosis ◽

Cell Types ◽

Receptor Expression ◽

Case Control Studies ◽

Platelet Surface ◽

Vitro Analysis ◽

And Function ◽

In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Download Full-text