The putative skin stem cells reproduce themselves seemingly indefinitely in the laboratory, the study found. When engrafted onto the backs of hairless mice, the cells also formed stretches of skin, tufts of hair, and sebaceous glands, which secrete an oily substance known as sebum that lubricates skin and hair.
"We've identified cells within skin that bear all the characteristics of true stem cells--the ability for self renewal and the multipotency required to differentiate into all lineages of epidermis and hair," said Elaine Fuchs, cell biologist at Rockefeller University and senior author of the study. "The results demonstrate for the first time that individual cells isolated from hair follicles can be cultured in the laboratory and retain a capacity to make multiple cell types when grafted."
The team's analysis of the versatile skin cells also offers new insights into the underlying genetic signature common to all stem cells, said the researchers.
Stem cells are undifferentiated cells whose daughters give rise to the specialized cell types that make up an organism. Embryonic stem cells, which emerge in the first days of an embryo's development, have the potential to differentiate, or specialize, into each of the 200 types of tissue in the body. In contrast, adult stem cells found in tissues throughout the body--including bone marrow, muscle, and skin--are defined by the ability to reproduce themselves and give rise to the full complement of cells that make up the specialized tissue in which they are found. By harnessing stem cells' natural capacity for replenishing cells, scientists hope to advance on new therapies designed to repair or replace damaged tissues and organs, said the researchers.
In mammalian skin, each hair follicle contains a reservoir of stem cells, known as the bulge, which can be mobilized to regenerate the new follicle with each hair cycle and to generate new epidermis during wound repair, the team explained.
Using new avenues to probe the cellular architecture of stem cells within the natural environment, or niche, of the hair follicle, the researchers discovered two distinct populations of resident cells within the bulge--one attached and one detached from the underlying extracellular matrix known as the basal lamina. New methods devised by the team then allowed them to isolate those two cell types for independent examination of their behavior and molecular properties.
While both cell types exhibited growth inhibition within their niche, the two underwent stem cell self-renewal in laboratory dishes, a quality that could prove clinically useful if it holds for stem cells derived from haired human skin, said Fuchs. Furthermore, clonal analyses revealed that both populations contained multipotent stem cells able to differentiate into all lineages of epidermis and hair following engraftment onto the backs of hairless mice. Remarkably, the graft even included formation of a structure within the follicle sharing many features of the stem cell niche, the team reported.
The two stem cell populations within the bulge exhibited significant differences in the activity of some genes. However, the team also found that about 14 percent of genes upregulated in embryonic, bone marrow, and neuronal stem cells also showed heightened activity in both groups of stem cells in the skin, further delineating the short list of "stemness" genes.
"These new data now document that single cells isolated from the bulge can self-renew and are multipotent, and thus possess the classical defining features of bona fide stem cells," according to the study's lead authors Cedric Blanpain and William Lowry, also of Rockefeller University.
Although their studies have so far been restricted to mice, the presence of such cells in the skin holds promise for regenerative medicine with regard to hair loss and wound healing, the researchers added. Once the essential genetic differences that distinguish embryonic and adult stem cells come to light, they said, the more accessible stem cells in skin might ultimately prove useful in the future for generating tissues lost in certain other types of diseases, such as some forms of blindness, or possibly even diabetes or Parkinson's.
"With debate about the cells' mutipotency within skin tissue settled, we can now ask whether the stem cells can also make other cell types in addition to hair and skin," Lowry said. "These results open the door to that possibility."
Cedric Blanpain, William E. Lowry, Andrea Geoghegan, Lisa Polak, and Elaine Fuchs: "Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche"
Published in Cell, Volume 118, Number 5, September 3, 2004, pages 635-648.