Live human hearts created in lab

They include growing an entire beating rat’s heart in the laboratory, which was reported in the journal Nature Medicine in 2008, and then a pig’s heart. Again the organ grew and started beating.

The team has also taken the ghost hearts of rats and pigs and seeded them with human stem cells. Again the cells multiplied rapidly, colonised the structure and started to beat independently. The beating strength was up to 25% that of a normal heart, but the fact that the hearts were beating at all was seen as a triumph.

Taylor hopes that, in the long term, the technology can be applied to overcome two of the biggest obstacles to transplant surgery. One is the shortage of organ donors; the other is the more complex problem of rejection, where people lucky enough to get transplants still have to take drugs for the rest of their lives to prevent their own immune systems attacking the organ that has saved them.

Taylor, who has had to carry out her human heart research in Spain because of an organ shortage in America, points out that there is no shortage of pigs from which to extract hearts if no human cadavers are available. Once such a heart has been stripped of pig cells and reseeded with human stem cells taken from a patient needing a new heart, there should be few rejections.

“We are a long way off creating a heart for transplant, but we think we’ve opened a door to building any organ for human transplant,” she said.

Regenerative science has seen a host of recent advances. Last year Laura Niklason, professor of biomedical engineering at Yale School of Medicine, Connecticut, published research in the journal Science describing how she had grown rat lungs in a laboratory using a similar technique to Taylor’s.

She then transplanted the artificial organs into living rats where they kept the creatures alive for up to two hours.

Last month Professor Shay Soker and colleagues at the Wake Forest Institute for Regenerative Medicine, North Carolina, described in the journal Hepatology how he had grown miniature “human” livers from animal ones.

The researchers removed livers from mice, rats, ferrets, rabbits and pigs and stripped them of their natural cells. Once cleansed, the “ghost” livers were seeded with immature human cells that multiplied and began functioning like normal human liver cells.

They wrote: “This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery.”

Soker’s colleagues at Wake Forest have gone further with other organs. Thirty people have received bladders grown in a technique developed by Professor Anthony Atala.

He takes healthy cells from a patient’s diseased bladder, grows them in the laboratory and applies them to a balloon-shaped scaffold made of collagen, the protein that forms the basis for most organ scaffolds. The organs take about eight weeks to grow and can then be transplanted into a patient.

A key question is how to ensure stem cells turn into the right thing — so they produce cardiac cells in the heart or liver cells in the liver.

Taylor believes natural scaffolds help achieve this, partly because the stem cells recognise their shape. It may also be because they are each impregnated with chemicals specific to the organ from which they were derived.

An artificial organ, says Taylor, requires three things: cells, a scaffold, and perfusion. (Think of it like a house: the scaffold is the foundation and the frame, the cells are the walls, floors, ceilings, furniture, and people who live there, and perfusion is the electricity and water and gas, along with cars and trucks and roads that deliver things to the house.)

Taylor's research has found that by removing the cells from the hearts of dead animals - and now humans as well - she can add stem cells and grow hearts that are starting to function like real hearts. The matrix somehow provides vital clues to the stem cells, telling them how to grow and function in their new environment. She has also now demonstrated that these animal and human cells will start to pulse and beat like a normal heart.

Such techniques represent huge advances, but for many researchers the heart will remain the greatest challenge, partly because cardiovascular disease is such a big killer. Heart and circulatory diseases cause more than one in three of all deaths in Britain.

The complexity of the heart is, however, the biggest challenge. Organs such as livers and kidneys may be intricate but they have no moving parts, nor complicated “wiring”.

Hearts, by contrast, must pump blood constantly and regularly and incorporate rapidly moving parts such as valves, complex plumbing and an electrical pacemaking system.

One fascinating finding from Taylor's research is that cells taken from a heart grow and behave differently depending on the scaffold to which they've been applied. The heart cells applied to a liver scaffold will behave more like liver cells than heart cells.

Taylor believes, however, that such problems will be solved: “One day we will be able to take a heart, probably from a pig, remove the cells and then replace them with cells grown from the patient’s own body.

“Then we would build a heart to match the patient and transplant it into them. That’s the dream.”

Reloading the Matrix: Doris Taylor Is Growing New Hearts

Larry Husten reports from the American College of Cardiology Conference in New Orleans. Larry Husten is the editor of Cardiobrief, an online resource for cardiologists and other healthcare professionals. This article has undergone some editing.

Doris Taylor wants to reload the matrix. A leading stem cell researcher at the University of Minnesota, Taylor is pioneering a new approach to transplantation, in which new hearts may one day be grown around the scaffold, or matrix, of a cadaver heart, most likely from an animal.

I usually avoid covering basic or blue-sky research on CardioBrief. But Jonathan Leake, science editor at The Sunday Times in London, asked me for some assistance covering Taylor’s presentations at the ACC so I checked out her talks here on Saturday. Taylor still has a long way to go, as she agrees along with everyone else, but her work now strikes me as a line of research worth following.

The idea behind Taylor’s research is to extract the protein-based scaffolds from the hearts of people who have died, stripping them of cells and leaving behind the organ’s tough protein skeleton which can then be seeded with stem cells in the hope they will grow into a new heart.

By using the matrix of animal hearts to grow human cells taken directly from the patient needing a new heart, Taylor hopes that her approach will overcome two of the biggest obstacles to transplant therapy: organ shortage and rejection.

Taylor’s research shows that the underlying matrix powerfully influences the fate of cells. In ways only dimly understood, the extracelleular matrix somehow imparts important functional clues to the cells. For instance, one fascinating finding is that cardiac derived progenitor cells will have a different morphology and pattern of gene expression depending on their matrix.

A leading cardiologist, Anthony De Maria, said that this finding was “stunning.” Further, cardiac cells growing on the matrix can be taught to beat in unison, though as yet the power of the contractions is not comparable to a functional heart. In fact, the same cells will differ when applied to the matrix of the right ventricle or the left ventricle.

In addition to the matrix and cells, a functioning organ needs to be perfused. Taylor shows that arterial and vascular cells end up in the vasculature, and endothelial cells reline the entire vascular tree where they will inhibit throbus formation.

Another fascinating direction of Taylor’s research involves applying a matrix “patch” in place of infarcted tissue. In rats she has grown new cells on the matrix implanted inside the living rat to prevent functional decline after MI. “The patch begins to prevent negative remodeling” within days after experimental MI in rats, reports Taylor.

Taylor has worked with a large variety of animal and now human matrices, as well as different types of animal and human cell types. In some of her newest research, performed with collaborators in Spain, where the local laws favor organ donation, human cells have been grown on human matrices. Although this is an important part of her research, Taylor says it’s not the goal of her research, since using human matrices will hinder the growth of the technique.

No one knows when or if a total heart transplant using these techniques will be attempted, but, says Taylor, “I predict in 5 years a piece of heart will be transplanted.”