Scientists in the US have grown the first functioning mini human heart models to help identify cardiac disorders in the lab.
The human heart organoids (hHOs), which have functioning chambers and vascular tissue, were created with stem cells to mimic the ‘nuts and bolts’ of how a fetal heart develops in the womb.
The tiny hHOs, which grew up to around 0.04 inches (1mm) in diameter after just 15 days, started beating at only around six days old.
Researchers say their little spherical hearts are the ‘most faithful human cardiovascular organoid model’ grown in vitro to date.
Lab-made miniature human heart models will help scientists better understand how defects like congenital heart disease develop, which affect 1 per cent of all live births.
‘With our heart organoids, we can study the origin of congenital heart disease and find ways to stop it,’ said Aitor Aguirre, assistant professor of biomedical engineering at Michigan State University.
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The human heart organoids (hHOs). hHOs started beating at around 6 days, were mostly spherical and grew up to around 1 mm in diameter by day 15
‘These minihearts constitute incredibly powerful models in which to study all kinds of cardiac disorders with a degree of precision unseen before.’
STEM CELLS: EMBRYONIC VS ADULT
Stem cells are special human cells that have the ability to develop into many different cell types, from muscle cells to brain cells.
In some cases, they also have the ability to repair damaged tissues.
Stem cells are divided into two main forms – embryonic stem cells and adult stem cells.
Embryonic stem cells can become all cell types of the body because they are pluripotent – they can give rise to many different cell types.
Adult stem cells are found in most adult tissues, such as bone marrow or fat but have a more limited ability to give rise to various cells of the body.
Meanwhile, induced pluripotent stem cells (iPSCs) are adult cells that have been genetically reprogrammed to be more like embryonic stem cells.
The hHOs showed very high similarity to human fetal hearts, both morphologically – in terms of structure – and cell-type complexity and have ‘sophisticated, interconnected internal chambers’.
One of the main issues facing the study of fetal heart development and congenital heart defects is access to a developing heart.
Researchers have previously been restricted to using of mammalian models and donated fetal remains.
‘Now we can have the best of both worlds, a precise human model to study these diseases – a tiny human heart – without using fetal material or violating ethical principles,’ Aguirre said.
The team used induced pluripotent stem cells (iPSCs) – adult cells taken from a patient – to trigger embryonic-like heart development in a dish.
iPSCs are adult cells that have been genetically reprogrammed to be more like embryonic stem cells, enabling the the development of an unlimited source of any type of human cell.
The use of iPSCs have allowed the generation of a functional mini heart after just over two weeks.
‘This process allows the stem cells to develop, basically as they would in an embryo, into the various cell types and structures present in the heart,’ said Aguirre.
The team say their method is scalable and has the potential to be replicated in other labs.
As well as congenital heart disease, the hHOs can help study chemotherapy-induced cardiotoxicity and the effect of diabetes during pregnancy on the developing fetal heart.
The hHO is ‘far from perfect’ compared with a human heart however, and future research at Michigan State University will aim to improve the models.
The hHOs showed very high similarity to human fetal hearts, both morphologically – in terms of structure – and cell-type complexity and have ‘sophisticated, interconnected internal chambers’
‘The organoids are small models of the fetal heart with representative functional and structural features,’ said Yonatan Israeli, a graduate student in the Aguirre Lab and first author of the study.
‘They are, however, not as perfect as a human heart yet. That is something we are working toward.’
The stem cells used for the process were obtained from consenting adults and therefore free of ethical concerns.
The study was funded by grants from the American Heart Association and the National Institutes of Health in the US, where heart disease is the top cause of death.
The work has been detailed further in the open access pre-print server bioRxiv.
The development of organoids has not been without controversy, as they are seen to represent a living entity.
A miniaturised ‘brain-in-a-bottle’ has been grown by stem cell scientists who hope it will lead to new treatments for neurological and mental diseases. The image was issued by Institute of Molecular Biotechnology in Vienna of a Cross section of an brain organoid
Experts last year writing in the journal Nature called for an ethical debate on human brain organoids.
According to Hank Greely, director of the Center for Law and the Biosciences at Stanford University in California and one of the authors of the report, organoids were not at a sophisticated enough stage of development to raise real concerns.
However, he added, guidelines did need to start being developed for the future as there is no single ethical line when it came to organoids.
‘I’m confident they don’t think we’ve reached a Gregor Samsa state, where a person wakes up and finds he is an organoid,’ he said in reference to the 1915 novella by Franz Kafka.
THE POTENTIAL OF ORGANOIDS
Organoids are tiny, self-organised three-dimensional tissue cultures that are derived from stem cells.
Such cultures can be crafted to replicate much of the complexity of an organ, or to express selected aspects of it like producing only certain types of cells.
Organoids grow from stem cells – cells that can divide indefinitely and produce different types of cells as part of their progeny.
Scientists have learned how to create the right environment for the stem cells so they can follow their own genetic instructions to self-organise, forming tiny structures that resemble miniature organs composed of many cell types.
Organoids can range in size from less than the width of a hair to five millimetres.
There are potentially as many types of organoids as there are different tissues and organs in the body.
To date, researchers have been able to produce organoids that resemble the brain, kidney, lung, intestine, stomach, and liver, and many more are on the way.
This way of culturing tissues will give scientists a detailed view of how organs form and grow, providing them with new insights on human development and disease.
It will also give them the opportunity to see how drugs interact with these ‘mini-organs’, potentially revolutionising the field of drug discovery and opening new approaches to personalised medicine.
Last October, neuroscientists created mini-brains from human tissue that can feel and may even suffer.
Although the mini-brains are the size of peanut, they have been observed to develop spontaneous brainwaves, not unlike those that seen in premature babies.
Brain organoids are used to investigate such disorders as autism and schizophrenia, and the impact of Zika virus on the development of brains in the womb.
They may also be helpful in the investigation of Alzheimer’s, Parkinson’s, Preterm Hypoxia and eye conditions like macular degeneration.
The line between research on organoids and human experimentation, however, is unclear and remains to be established.
Elan Ohayon – director of the Green Neuroscience Laboratory in San Diego, California – and colleagues Ann Lam and Paul Tsang argue that checks need to be in place to stop organoids from enduring pain.
‘If there’s even a possibility of the organoid being sentient, we could be crossing [a] line,’ Dr Ohayon told the Guardian.
Source: Harvard University