Stem cells found in adult peripheral nervous system

August 14, 2002

ANN ARBOR, MI - Scientists at the University of Michigan Medical School have found neural crest stem cells - primitive cells that generate the peripheral nervous system - in the gut of adult laboratory rats. The U-M discovery upsets the widely held belief that neural crest stem cells disappear in animals before birth, once the peripheral nervous system develops.

U-M scientists reported their research results in two papers published in the Aug.15 issue of Neuron.

"We know that stem cells exist in the adult central nervous system," says Sean J. Morrison, Ph.D., a Howard Hughes Medical Institute assistant investigator and a U-M Medical School assistant professor of internal medicine and of cell and developmental biology. "But this is the first indication that they also remain in the peripheral nervous system - not only after birth, but into adult life."

Morrison explains that the central and peripheral nervous systems develop from two different locations in the early embryo. Stem cells in one area create the central nervous system's brain and spinal cord. Stem cells from another area, called the neural crest, give rise to peripheral neurons and glial cells that control gut function, regulate the fight-or-flight response and make it possible for us to have a sense of touch. Glial cells are supportive cells for the nervous system.

"We don't know what these neural crest stem cells are doing in the gut or whether they persist into adult life in humans, as they do in rats," says Morrison. "The importance of the study is that it provides the first evidence that stem cells persist in the adult peripheral nervous system. Our results will lead to additional research, which could lead to new ways of using stem cells to promote peripheral nervous system repair after injury or disease."

Suzanne Bixby, a research associate in Morrison's laboratory, and Genevieve M. Kruger, a student in the U-M Medical School's Medical Scientist Training Program, used flow cytometry technology to isolate the stem cells described in the Neuron articles. Cited as first authors of the papers, Bixby worked with neural crest stem cells from embryonic rat gut and sciatic nerves, while Kruger focused on stem cells in postnatal and adult rat gut.

"We decided to look for stem cells in postnatal gut tissue, because that's where development of the peripheral nervous system continues the longest," Kruger says.

The stem cells were rare and difficult to find, according to Bixby. Even in embryonic gut tissue, only one to two percent of all cells turned out to be neural crest stem cells.

To demonstrate that they were true stem cells with the ability to self-renew and form new peripheral nervous system cells, Bixby cultured individual neural crest stem cells taken from rat gut at Day 14 of embryonic development, while Kruger used single cells from rats that were 15-to-110 days old.

Whether from embryonic or adult rat gut, individual neural crest stem cells gave rise to thousands of neurons, glia and smooth muscle cells. Even though activity declined with age, stem cells could still be isolated from the oldest rat in the study, which was 110 days old.

One of the most intriguing findings of the U-M study, according to Morrison, was the discovery that neural crest stem cells have the power to control their own developmental destiny.

"One reason why different types of cells exist in different parts of the nervous system is that they develop from different types of stem cells," Morrison explains. "This is the first study to clearly show there are cell-intrinsic differences between stem cells in different parts of the nervous system at the same time in development, and these innate differences have real functional consequences."

Jack T. Mosher, a post-doctoral fellow in Morrison's lab, had the challenging job of transplanting neural crest stem cells from rats into developing peripheral nerves in chick embryos. Mosher used stem cells from rats at identical stages of embryonic development (Day 14), but some of the stem cells were isolated from embryonic rat gut and others from the sciatic nerve.

"Sciatic nerve neural crest stem cells developed into glial cells, while stem cells from the gut became neurons," Morrison says. "Stem cells from different regions of the nervous system differ in their responsiveness to environmental signals that stimulate neural development. Some cells were more responsive to signals promoting neuronal development, while others were more responsive to signals promoting glial development."

Morrison cautions that it's too early to make predictions on whether the new stem cell discovery will have medical applications. "We are just at the stage of imagining new approaches," he says. "Our immediate goal is to understand the function of these cells and find out whether they exist in humans. If so, it could change the way we think about promoting repair in the adult peripheral nervous system."

Sean Morrison was one of 100 young innovators profiled in the June 2002 issue of Technology Review . The honorees work in "hot spot" research areas with the potential to transform existing industries and create new ones.
Morrison's stem cell research is supported by the National Institutes of Health, the Searle Scholars Program and the Howard Hughes Medical Institute. The U-M has filed a patent application on the research findings.

Additional U-M collaborators were Nancy M. Joseph, a student in the Medical School's Medical Scientist Training Program, and Toshihide Iwashita, Ph.D., a post-doctoral fellow. Joseph defined the expression patterns of environmental factors that control stem cell differentiation. Iwashita determined where neural crest stem cells were most likely to be located in the gut.

Additional Contact Information:

University of Michigan Health System

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to