Growing out a little heart...

I attended a fascinating lecture today by Dr. Joshua Hare, MD, from Johns Hopkins University here at the University of Chicago. He talked about research he is doing using stem cells from bone marrow to repair hearts damaged by heart attacks.

While the public debate over embryonic stem cells continues to rage, many researchers are avoiding that ethical quagmire altogether and simply using the stem cells that already exist in the body for their research. It has long been known that some adult stem cells exist in the bone marrow because they are responsible for generating new white and red blood cells, which the body is continually replenishing as old ones die out.

Embryonic stem cell researchers would contend that adult stem cell are not as useful as the embryonic ones because they are too mature (or differentiated). They believe that only embryonic stem cells that will allow us to achieve the goal of "regrowing" organs damanged by injury or disease.

In his presentation, however, Dr. Hare pointed out that one of the biggest problems with embryonic stem cells is that they tend to form teratomas, a type of tumor. Adult stem cells, when implanted or injected into damaged tissue, do not seem to be as likely to form such teratomas.

Dr. Hare discussed his research in which they took a certain type of adult stem cells from the bone marrow, called mesenchymal stem cells (MSCs), and injected them into heart tissue that was damaged by a heart attack. Tissue that is damaged by a heart attack is dead tissue, because it no longer receives any blood flow. This dead tissue can no longer contract, or beat, and is usually weaker than the remaining heart tissue.

After about two months, Dr. Hare's team found that new heart tissue had grown in the spot where the mesenchymal cells were injected. Not only that, but this new tissue was actively beating, in sync with the rest of the heart! An area of the heart that was totally dead and not beating had regained its function and started contracting again.

The question for Dr. Hare and his team is whether this new tissue is the result of the MSCs transforming into cardiac myocytes (the cells that make the heart beat) or whether the MSCs stimulate the heart to produce these myocytes.

This second hypothesis comes from the fact that adult stem cells have been discovered in the heart. In 2004, research by Messina established the existence of cardiac adult stem cells. This was a major breakthrough because the prevailing dogma has been that our organs are "terminally differentiated", that they have reached the limit of their maturation, and thus do not have adult stem cells. Messina's research, and research like hers, is starting to reveal that stem cells may be more ubiquitous than previously imagined and that our organs may be more flexible and dynamic than we ever thought.

Dr. Hare's technique of injecting MSCs into damaged cardiac tissue (called "cellular cardiomyoplasty") is exciting because it offers the chance for therapy that actually reverses the damage of a heart attack. This is far ahead of current therapy which assumes that a heart attack will cause a certain amount of irreversible damage (depending on how large the heart attack is) with therapy aimed to minimize its progression. This has given rise to the concept of "cardiac regenerative therapy" in which one can actually regenerate at least some of the dead tissue and its function.

These initial experiments were done in pigs and Dr. Hare and his team have already moved into Phase I clinical trials, to see if they can replicate their success in humans. If so, it heralds an exciting new era of treatment in medicine.

Sources:

1. "Cardiac repair with intramyocardial injectionof allogeneic mesenchymal stem cells after myocardial infarction." Luciano C. Amado et al. Proc Natl Acad Sci USA. 2005 Aug 9;102(32):11474-9.

2. "Isolation and expansion of adult cardiac stem cells from human and murine heart." Elisa Messina et al. Circ Res. 2004 Oct 29;95(9):911-21.