scholarly journals Human cerebral organoids and consciousness: a double-edged sword

2020 ◽  
Vol 38 (2) ◽  
pp. 105-128 ◽  
Author(s):  
Andrea Lavazza
Keyword(s):  
Moral Status ◽  
Ethical Issues ◽  
Developmental Process ◽  
Three Dimensional ◽  
Human Consciousness ◽  
Preterm Babies ◽  
Test Treatments ◽  
In Vitro Cell Cultures ◽  
Further Development

AbstractHuman cerebral organoids (HCOs) are three-dimensional in vitro cell cultures that mimic the developmental process and organization of the developing human brain. In just a few years this technique has produced brain models that are already being used to study diseases of the nervous system and to test treatments and drugs. Currently, HCOs consist of tens of millions of cells and have a size of a few millimeters. The greatest limitation to further development is due to their lack of vascularization. However, recent research has shown that human cerebral organoids can manifest the same electrical activity and connections between brain neurons and EEG patterns as those recorded in preterm babies. All this suggests that, in the future, HCOs may manifest an ability to experience basic sensations such as pain, therefore manifesting sentience, or even rudimentary forms of consciousness. This calls for consideration of whether cerebral organoids should be given a moral status and what limitations should be introduced to regulate research. In this article I focus particularly on the study of the emergence and mechanisms of human consciousness, i.e. one of the most complex scientific problems there are, by means of experiments on HCOs. This type of experiment raises relevant ethical issues and, as I will argue, should probably not be considered morally acceptable.

scholarly journals ‘Consciousnessoids’: clues and insights from human cerebral organoids for the study of consciousness

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Andrea Lavazza
Keyword(s):  
Neural Development ◽  
Ethical Issues ◽  
Three Dimensional ◽  
Three Dimensional Model ◽  
Fast Pace ◽  
Strict Regulation ◽  
Muscle Contract ◽  
Preterm Babies ◽  
Structure And Functions

Abstract Human cerebral organoids (HCOs) are an in vitro three-dimensional model of early neural development, aimed at modelling and understanding brain development and neurological disorders. In just a few years, there has been a rapid and considerable progress in the attempt to create a brain model capable of showcasing the structure and functions of the human brain. There are still strong limitations to address, including the absence of vascularization that makes it difficult to feed the central layers of organoids. Nevertheless, some important features of the nervous system have recently been observed: HCOs manifest electrical activity, are sensitive to light stimulation and are able to connect to a spinal cord by sending impulses that make a muscle contract. Recent data show that cortical organoid network development at 10 months resembles some preterm babies’ electroencephalography (EEG) patterns. In the light of the fast pace of research in this field, one might consider the hypothesis that HCOs might become a living laboratory for studying the emergence of consciousness and investigating its mechanisms and neural correlates. HCOs could be also a benchmark for different neuroscientific theories of consciousness. In this paper, I propose some potential lines of research and offer some clues and insights so as to use HCOs in trying to unveil some puzzles concerning our conscious states. Finally, I consider some relevant ethical issues regarding this specific experimentation on HCOs and conclude that some of them could require strict regulation in this field.

scholarly journals Gut organoids: mini-tissues in culture to study intestinal physiology and disease

2019 ◽  
Vol 317 (3) ◽  
pp. C405-C419 ◽  
Author(s):  
Mohammad Almeqdadi ◽  
Miyeko D. Mana ◽  
Jatin Roper ◽  
Ömer H. Yilmaz
Keyword(s):  
Cell Lines ◽  
Three Dimensional ◽  
Gastrointestinal Diseases ◽  
In Vivo Models ◽  
Intestinal Physiology ◽  
Microbe Interactions ◽  
Immortalized Cell ◽  
In Vitro Cell Cultures

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.

scholarly journals Challenges for Production of Human Transplantable Organ Grafts

Cell Medicine ◽  
2017 ◽  
Vol 9 (1-2) ◽  
pp. 9-14 ◽  
Author(s):  
Eiji Kobayashi
Keyword(s):  
Research Methods ◽  
Three Dimensional ◽  
Research Results ◽  
Human Organs ◽  
The Third ◽  
Further Development

The described research methods explain how you could generate a three-dimensional kidney, based on recent research results. The first method is to fabricate human organs in a pig body. The second is to transplant the so-called “organ bud” into a patient's body for further development. The third method is to regenerate organs by filling cells into the cytoskeleton as a scaffold. Research for the in vitro fabrication of organ buds has been elaborately accelerated. The organ bud transplantation has been confronted with issues of continuity with the original organs, so the development of technology for achieving continuity between a transplanted organ bud and the existing organs is progressing well. The “organ fabrication” methodology, whereby cells are placed into completely decellularized organs, is supported by recent research results using pig organs taking the size of humans into consideration.

scholarly journals Developments and Opportunities for 3D Bioprinted Organoids

2021 ◽  
Vol 7 (3) ◽  
pp. 364
Author(s):  
Ya Ren ◽  
Xue Yang ◽  
Zhengjiang Ma ◽  
Xin Sun ◽  
Yuxin Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Materials Science ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Key Characteristics ◽  
And Function ◽  
Further Development

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.

scholarly journals Cerebral organoids: ethical issues and consciousness assessment

2018 ◽  
Vol 44 (9) ◽  
pp. 606-610 ◽  
Author(s):  
Andrea Lavazza ◽  
Marcello Massimini
Keyword(s):  
Ethical Issues ◽  
Personalised Medicine ◽  
Three Dimensional ◽  
Cell Types ◽  
Human Embryos ◽  
Specific Cell ◽  
Neural Connections ◽  
Structural And Functional Properties ◽  
Organ Specific

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids (ie, human embryos) and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or (which is more likely) will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available (the Perturbational Complexity Index, a metric that is directly inspired by the main postulate of the Integrated Information Theory of consciousness), which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary.

scholarly journals Shape fidelity and sterility assessment of 3D printed polycaprolactone and hydroxyapatite scaffolds

2021 ◽  
Vol 28 (9) ◽  
Author(s):  
Franca Scocozza ◽  
Mirena Sakaj ◽  
Ferdinando Auricchio ◽  
Stefania Marconi ◽  
Pietro Riello ◽  
...  
Keyword(s):  
Thermal Analyses ◽  
Three Dimensional ◽  
The United States ◽  
United States Pharmacopoeia ◽  
3D Printed ◽  
The Fourier Transform ◽  
The Stability ◽  
In Vitro Cell Cultures ◽  
3D Printing Technique

AbstractPolycaprolactone (PCL) and hydroxyapatite (HA) composite are widely used in tissue engineering (TE). They are fit to being processed with three-dimensional (3D) printing technique to create scaffolds with verifiable porosity. The current challenge is to guarantee the reliability and reproducibility of 3D printed scaffolds and to create sterile scaffolds which can be used for in vitro cell cultures. In this context it is important for successful cell culture, to have a protocol in order to evaluate the sterility of the printed scaffolds. We proposed a systematic approach to sterilise 90%PCL-10%HA pellets using a 3D bioprinter before starting the printing process. We evaluated the printability of PCL-HA composite and the shape fidelity of scaffolds printed with and without sterilised pellets varying infill pattern, and the sterility of 3D printed scaffolds following the method established by the United States Pharmacopoeia. Finally, the thermal analyses supported by the Fourier Transform Infrared Spectroscopy were useful to verify the stability of the sterilisation process in the PCL solid state with and without HA. The results show that the use of the 3D printer, according to the proposed protocol, allows to obtain sterile 3D PCL-HA scaffolds suitable for TE applications such as bone or cartilage repair.

scholarly journals Developmental and Functional Hair Cell-Like Cells Induced by Atoh1 Overexpression in the Adult Mammalian Cochlea In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Lingyi Kong ◽  
Yuan Xin ◽  
Fanglu Chi ◽  
Jie Chen ◽  
Juanmei Yang
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Adult Mouse ◽  
Developmental Process ◽  
Three Dimensional ◽  
Potassium Currents ◽  
Outer Hair Cells ◽  
Adult Mice ◽  
Delivery Vector

Hair cells (HCs) in the mammalian cochleae cannot spontaneously regenerate once damaged, resulting in permanent hearing loss. It has been shown that Atoh1 overexpression induces hair cell-like cells (HCLCs) in the cochlea of newborn rodents, but this is hard to achieve in adult mammals. In this study, we used a three-dimensional cochlear culture system and an adenoviral-mediated delivery vector to overexpress Atoh1 in adult mouse cochleae. HCLCs were successfully induced from 3 days after virus infection (3 DVI) in vitro, and the number increased with time. HCLCs were myosin7a positive and distinguishable from remnant HCs in a culture environment. Meanwhile, patch-clamp results showed that noninactive outward potassium currents (sustained outward potassium currents) could be recorded in HCLCs and that their magnitude increased with time, similar to normal HCs. Furthermore, transient HCN currents were recorded in some HCLCs, indicating that the HCLCs experienced a developmental stage similar to normal HCs. We also compared the electrophysiological features of HCLCs from adult mice with native HCs and found the HCLCs gradually matured, similar to the normal HCs. Meanwhile, HCLCs from adult mice possessed the same bundles as developmental HCs. However, these HCLCs did not express prestin, which is a special marker for outer hair cells (OHCs), even at 13 DVI. These results demonstrate that Atoh1 overexpression induces HCLC formation in the adult mammalian cochlea and that these HCLCs were functional and experienced a developmental process similar to that of normal HCs.

scholarly journals Advances in Female Germ Cell Induction from Pluripotent Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Maisumu Gulimiheranmu ◽  
Xinjie Wang ◽  
Junmei Zhou
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Germ Cells ◽  
Pluripotent Stem Cells ◽  
Ethical Issues ◽  
Developmental Process ◽  
Human Embryos ◽  
Human Female ◽  
Germ Cell Differentiation

Germ cells are capable of maintaining species continuity through passing genetic and epigenetic information across generations. Female germ cells mainly develop during the embryonic stage and pass through subsequent developmental stages including primordial germ cells, oogonia, and oocyte. However, due to the limitation of using early human embryos as in vivo research model, in vitro research models are needed to reveal the early developmental process and related mechanisms of female germ cells. After birth, the number of follicles gradually decreases with age. Various conditions which damage ovarian functions would cause premature ovarian failure. Alternative treatments to solve these problems need to be investigated. Germ cell differentiation from pluripotent stem cells in vitro can simulate early embryonic development of female germ cells and clarify unresolved issues during the development process. In addition, pluripotent stem cells could potentially provide promising applications for female fertility preservation after proper in vitro differentiation. Mouse female germ cells have been successfully reconstructed in vitro and delivered to live offspring. However, the derivation of functional human female germ cells has not been fully achieved due to technical limitations and ethical issues. To provide an updated and comprehensive information, this review centers on the major studies on the differentiation of mouse and human female germ cells from pluripotent stem cells and provides references to further studies of developmental mechanisms and potential therapeutic applications of female germ cells.

scholarly journals Organoid Technology: A Reliable Developmental Biology Tool for Organ-Specific Nanotoxicity Evaluation

2021 ◽  
Vol 9 ◽  
Author(s):  
Minakshi Prasad ◽  
Rajesh Kumar ◽  
Lukumoni Buragohain ◽  
Ankur Kumari ◽  
Mayukh Ghosh
Keyword(s):  
Ethical Issues ◽  
Animal Experiments ◽  
Three Dimensional ◽  
Toxicity Assessment ◽  
Dimensional Structure ◽  
Phase Development ◽  
Organ Specific ◽  
Nano Science

Engineered nanomaterials are bestowed with certain inherent physicochemical properties unlike their parent materials, rendering them suitable for the multifaceted needs of state-of-the-art biomedical, and pharmaceutical applications. The log-phase development of nano-science along with improved “bench to beside” conversion carries an enhanced probability of human exposure with numerous nanoparticles. Thus, toxicity assessment of these novel nanoscale materials holds a key to ensuring the safety aspects or else the global biome will certainly face a debacle. The toxicity may span from health hazards due to direct exposure to indirect means through food chain contamination or environmental pollution, even causing genotoxicity. Multiple ways of nanotoxicity evaluation include several in vitro and in vivo methods, with in vitro methods occupying the bulk of the “experimental space.” The underlying reason may be multiple, but ethical constraints in in vivo animal experiments are a significant one. Two-dimensional (2D) monoculture is undoubtedly the most exploited in vitro method providing advantages in terms of cost-effectiveness, high throughput, and reproducibility. However, it often fails to mimic a tissue or organ which possesses a defined three-dimensional structure (3D) along with intercellular communication machinery. Instead, microtissues such as spheroids or organoids having a precise 3D architecture and proximate in vivo tissue-like behavior can provide a more realistic evaluation than 2D monocultures. Recent developments in microfluidics and bioreactor-based organoid synthesis have eased the difficulties to prosper nano-toxicological analysis in organoid models surpassing the obstacle of ethical issues. The present review will enlighten applications of organoids in nanotoxicological evaluation, their advantages, and prospects toward securing commonplace nano-interventions.

RECONSTRUCTION OF FUNCTIONAL EQUIVALENTS OF THE SKIN USING CELL AND TISSUE TECHNOLOGIES

2021 ◽  
Vol 1 (19) ◽  
pp. 193-194
Author(s):  
O.S. Rogovaya ◽  
E.S. Chermnykh ◽  
E.O. Osidak ◽  
E.V. Kiseleva ◽  
A.L. Rippa ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Chronic Wounds ◽  
Healing Process ◽  
Three Dimensional ◽  
Skin Equivalent ◽  
Type I ◽  
Human Tissues ◽  
Further Development

The work is based on obtaining a living skin equivalent based on a three-dimensional scaffold consisting of type I collagen and other components of the extracellular matrix. The composition of the equivalent includes dermal and epidermal cells, it significantly accelerates and normalizes the healing process of chronic wounds. The living equivalent of the skin is a start for the further development of tissue-engineered constructs-analogs of skin and equivalents of other human tissues: at present, in particular, work is underway to study the stromal fractions of the dermis to control epithelial-mesenchymal interactions in vitro.

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