Can Stem Cells from the Bone Marrow Really Cure Heart Disease?
By Susan Garfinkel

Since stem cells can develop into many different cell types, it is not surprising that scientists are enthusiastic about their potential use for tissue repair and regeneration in patients with various diseases. There is a great deal of excitement and controversy in the field of stem cell biology, with intense debate regarding whether adult stem cells, which come from specialized tissue, can efficiently develop into cell types different from those found in tissue from which they have been isolated. The term used to describe the ability of adult stem cells to change from one cell type to another completely different cell type is referred to as the plasticity of adult stem cells.

Several reports in the scientific literature have suggested that adult stem cells from bone marrow can transdifferentiate into completely different cell types, like heart muscle cells or brain cells, for example. Other studies have reported that when bone marrow stem cells are transplanted into different tissue, fusion occurs between the transplanted stem cells and the different cell types residing at the site; thus, stem cells do not really change into different cell types. This type of controversy is part of the normal scientific discovery process, and as scientists continue to study stem cells, new information will help to support one theory or the other.

Three years ago, a team of researchers published an exciting paper that suggested that bone marrow stem cells could replace heart muscle that was lost after a heart attack. This electrifying work stimulated many researchers to further investigate these results to determine whether it would be feasible to develop therapies for patients, and clinical trials were initiated. In two new papers recently published in the journal Nature, two research teams challenged these original findings.

Both groups of authors used highly advanced methods to determine whether bone marrow stem cells could become heart cells in the damaged hearts of mice, and then restore function. They looked at specific markers that tagged the bone marrow stem cells – a marker called LacZ in one case and another marker called green fluorescent protein (GFP) in the other -- and after transplantation of the bone marrow cells, tracked whether these markers could be found in cells identified as heart muscle cells. They found that neither marker could be detected in heart cells, suggesting that the tagged bone marrow stem cells did not become heart muscle cells. The reason for the discrepancy between these results and those in earlier studies is not clear, but may result from the great difficulty to track a few transplanted cells within an intact organ and the use of different, now more sensitive detection techniques. For more detailed information read the News and Views article in Nature that accompanied the two reports.

These new reports in Nature highlight an ongoing debate in the stem cell community: whether blood forming stem cells taken from bone marrow can be used to regenerate organs other than blood. Similar questions surround many reports touting the capabilities of other adult stem cells.

The question becomes why is interpretation of studies using adult stem cells so problematic? Several reasons have been brought forth. There are technical issues. For example, there are no standardized protocols for the isolation of blood forming stem cells from the bone marrow. As these cells are not abundant, it is difficult to ascertain whether two groups are isolating and working with the exact same cells. Further, adult stem cells are isolated from human tissue, and every human donor is genetically different from the next, including their stem cells. There are also considerable differences in reagents used in research and their quality from batch to batch. This can result in dramatically different experimental outcomes.

A part of the challenge in carrying out scientific research is that even when using exactly the same reagents and the same cell donor, two independent groups can sometimes obtain different, even contradictory results. This is a common and accepted phenomenon in research, which is why results reported by one group have to be replicated by at least one other group before being accepted as valid by the community. Often, groups reporting contradictory results openly discuss problems and exchange reagents. This has been somewhat neglected because of the high stakes and potential benefits in the stem cell research field. Also, the entire debate has gained much more public attention than it would have in other research fields.

The recently published papers in Nature emphasize the controversies that exist in this field and the importance that more robust science is needed to evaluate adult stem cells and their therapeutic potential, in order to bring efficient stem cell therapies into the clinic.

Susan Garfinkel, PhD, is a Scientist-Investigator for the Office of Research Integrity, and Chair of the ISSCR Education Committee.

Updated: February 2, 2005