The role of stem cells in cardiac regeneration

The role of stem cells in cardiac regeneration

Anke M. Smits, Patrick van Vliet, Rutger J. Hassink, Marie-José Goumans, Pieter A. Doevendans
J. Cell. Mol. Med. Vol 9, No 1, 2005 pp. 25-36

Summary:
In stem cell research, one major focus has been to determine which populations of cells hold the greatest potential for various stem cell-based therapies. For example, bone marrow-derived stem cells have emerged as candidates for cardiomyocyte repair. However, due partly to the wide number of papers being published from different research groups, the results of different studies are sometimes difficult to compare, and drawing meaningful conclusions from the body of work in this field can be a challenge. This paper summarizes the work that had been done on stem cells as of 2005, specifically focusing on the viability of using different populations of bone marrow-derived stem cells as cardiac progenitor cells.

The paper begins with an overview of stem cell research in general, comparing human embryonic stem cells (hESCs) and somatic stem cells and concluding that hESCs suffer from several disadvantages that make them less-than-ideal candidates for regenerative therapy. These include the possibility of rejection by the host due to their allogenic origin, as well as the intense ethical debate surrounding the isolation and use of hESCs. Somatic stem cells do not pose these challenges, and are thus probably more useful for cell regeneration therapies.

The most widely-studied populations of somatic stem cells are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSC), which come from bone marrow. The authors include a chart summarizing many experimental findings about HSC and MSC differentiation; only MSCs have been shown to differentiate into cardiomyocytes in vitro, and the authors summarize the studies that led to these findings. In the experiments described, MSC cardiomyocyte differentiation was validated using methods such as cardiomyocyte-specific protein assays and gene expression assays; further confirmation that the MSCs had differentiated into cardiomyocytes was found when the cells began to exhibit myogenic behavior, i.e. they began to “beat” and exhibit cardiomyocyte-like action potentials. In vivo studies have also shown differentiation capability of MSCs as well as HSCs, and various growth factors and conditions have been shown to have an effect on differentiation of these cells.

The paper also discusses “cardiomyocyte precursor cells,” or CPCs, which have been shown to undergo cardiac differentiation but whose origins (i.e. where the CPCs come from, or what exactly they are) are still under investigation. CPCs might reside in the heart from fetal development onwards, or could be "recruited" when needed (e.g., from bone marrow or somewhere in the circulatory pathway). Several studies on the topic of CPCs are discussed in this paper, but the findings do not point to a clear answer, and the origins of CPCs are still unknown. The paper concludes by saying that although a lot of progress has been made in stem cell research, there are still some key questions about stem cell differentiation that remain to be solved, and the authors stress the point that we're still a long way from seeing widespread clinical applications of stem cells for cardiac regeneration.

Significance

As the authors state in the paper, stem cell research has been operating at a fever pitch in recent years, and it can be difficult to keep track of all the findings being published by various research groups. That’s part of the reason I decided to choose a summary paper – I thought it would be the best way to get a sense of the work that has been done, as well as the questions that remain unanswered. I thought it was interesting that scientists have been able to induce cell differentiation in HSCs and MSCs, and simultaneously have found CPCs that they know differentiate into cardiomyocytes, but that no one has been able to determine with certainty the origin of these CPCs. It’s an example of how scientific research on a given topic can progress in a few different directions at once, and eventually (hopefully) the different directions will converge in a clear answer.