Newly Identified Stem Cell Population In Skin Is Responsible for Wound Healing

BRUSSELS, Belgium, September 3, 2012 – Skin researchers from the Universitй Libre de Bruxelles, Belgium have discovered a new stem cell population in skin that is responsible for tissue repair.

Our skin protects our bodies from the environment and its toxins, hard knocks, and extremes of temperature, pressure and so on. Consequently, the skin is subject to constant replacement and dead cells are sloughed off and replaced throughout our lifetimes.

However, the number of cells generated by the skin must exactly replace those that are lost. Different theories have been proposed to explain how this delicate balance is maintained.

In this new study, Prof. Cйdric Blanpain and his colleagues have collaborated with Prof. Benjamin Simons at the University of Cambridge, U.K. to show that a new population of stem cells in the skin give rise to a population of progenitor cells that are involved in the daily maintenance of the upper layers of the skin (epidermis). In fact, these stem cells are the major contributor during wound healing.

Blanpain and others used a novel genetic lineage tracing protocol to fluorescently mark two distinct skin cell populations, and follow their survival and contribution to the maintenance of the epidermis over time. These labeling experiments demonstrated the existence of two types of dividing cells. One cell population showed very long-term survival potential while the other population is progressively lost over time.

With Benjamin D. Simons, Blanpain and his lab devised a mathematical model of their lineage tracing analysis. The model suggested that skin, particularly the epidermis, contains a population of stem cells that divide very slowly that give rise to very fast dividing progenitor cells that ensure the daily maintenance of the skin epidermis. Cell proliferation patterns confirmed the existence of slow cycling stem cells. Furthermore, gene profiling experiments showed that the stem and the progenitor cells are characterized by distinct patterns of gene expression.

By assessing the contribution of these two cell populations during wound healing, they showed that only the skin stem cells were capable of extensive tissue regeneration and undergo major expansion during this repair process. The progenitors, on the other hand, did not expand significantly, but provided a short-lived contribution to the wound healing response.

These data resolve a long-standing debate regarding the cell populations that contribute to wound healing in the skin. Apparently, these epidermal stem cells are the main players during wound healing.

“It was amazing to see these long trails of cells coming from a single stem cell located at a very long distance from the wound to repair the epidermis,” said Dr.  Blanpain, who was the senior author of the study.

Thus the slow-dividing stem cells promote tissue repair and more the more rapidly dividing progenitors ensure the daily maintenance of the epidermis.

Interestingly, similar populations of slow cycling stem cells that can be rapidly mobilized in case of sudden need have been observed in other tissues, such as the blood, muscle and hair follicle. The division between rapidly cycling progenitors and slow cycling stem cells seems to be relatively conserved across the different tissues.

Of course, these findings may have important implications in regenerative medicine; in particular for skin repair in severely burnt patients or in chronic wounds.

Mouse Heart-Specific Stem Cells Potentially Offer Hope For Heart Attack Patients

Biomedical researchers from the University of California, San Francisco (UCSF) have published a stem cell experiment in mice that might provide another way to fix damaged heart muscle in heart attack patients. If these results pan out, they could potentially could increase heart function, minimize scar size, promote the growth of new blood vessels around the heart, and doo all this while avoiding the risk to tissue rejection.

Sounds too good to be true? It was published in PLoS ONE. You can read about it here.

To summarize the experiments, researchers isolated a new heart-specific stem cell from the heart tissue of middle-aged mice. When cultured in a laboratory dish, the cells had the ability to differentiate into heart muscle cells that beat in the culture dish. However, these same cells could also become blood vessels, or smooth muscle, which surrounds blood vessels and regulates the diameter of the vessels. All of these tissues are essential for the heart to work and properly function.

After showing that these cells could be grown in the laboratory in converted into heart-specific cell types, this research group examined the ability of these cells to do the same thing inside a living organism. After expanding the cells in culture, they transplanted them into the hearts of sibling mice that had the same genetic lineage as the mice from which the heart stem cells had been isolated in the first place. This prevented the possibility of the immune system of the recipient mice from attacking and rejecting the implanted cells. The implanted stem cells made blood vessels and also formed smooth muscle. The increased blood flow improved heart function.

Even more exciting, these heart specific stem cells are found in all four chambers of the heart. The “cardiosphere-derived cells” (CDCs) that have been used in other clinical trials are only found in the upper chambers of the heart (atria), and express slightly different cell surface proteins. When grown in culture, these cells grow into spheres of cells that are known as “cardiospheres.”  These new heart-specific stem cells are more widely located in the heart, which means that it is possible to isolate them from patients’ hearts by doing ventricular or atrial biopsies. Biopsies of the right ventricle are among the safest procedures for procuring heart cells from live patients. This procedure is relatively easy to perform and does not adversely affect the patient.

The paper’s first author, Jianqin Ye, PhD, MD, senior scientist at UCSF’s Translational Cardiac Stem Cell Program, said, “These findings are very exciting . . . we showed that we can isolate these cells from the heart of middle-aged animals, even after a heart attack. . . we determined that we can return these cells to the animals to induce repair.”

Senior author Yerem Yeghiazarians, MD, director of UCSF’s Translational Cardiac Stem Cell Program and an associate professor at the UCSF Division of Cardiology, agreed with Ye’s assessment: “The finding extends the current knowledge in the field of native cardiac progenitor cell therapy. Most of the previous research has focused on a different subset of cardiac progenitor cells. These novel cardiac precursor cells appear to have great therapeutic potential.”

Yeghiazarians hopes that those patients who have suffered severe heart failure after a heart attack or have enlargement of the heart (cardiomyopathy) could still be treated with their own heart-specific stem cells to improve their overall health and heart function. Because these cells would come from the patients, there would be no concern of cell rejection after therapy.

These heart-specific stem cells are also known as Sca-1+ stem cells. Sca-1 is a small cell surface protein that is involved in cell signaling. These heart-specific Sca-1+ cells also express a transcription factor called Islet (Isl-1). These cells are known to play an important role in heart development. Most of the previous research on heart stem cells has examined different subset of cells known as “c-kit” cells. Sca-1+ cells, like the c-kit cells, are located within a larger clump of cells called cardiospheres.

To isolate the Sca-1+ cells, Yeghiazarians’ group devised ways to separate the Sca-1-expressing cells that were also expressing high levels of Isl-1. Sca-1 is rather easy to use for isolation, since it is a cell surface protein, but Isa-1 is a nuclear protein and is less useful for isolation purposes.

Yeghiazarians proposed that the co-expression of these two molecules that are also made during heart development suggests a strategy for heart therapy: “Heart disease, including heart attack and heart failure, is the number one killer in advanced countries. It would be a huge advance if we could decrease repeat hospitalizations, improve the quality of life and increase survival.” By giving the heart cells that are extremely similar to those cells that help construct it during development; those same cells could reconstruct the heart when it starts to fail.

More studies are on the board for the future, and these animal studies might lead to future clinical trials.