From: Subject: Role of the nervous system in regulating stem cells discovered Date: Mon, 15 May 2006 17:25:48 +0200 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01C67844.9B0FC8D0" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.2869 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01C67844.9B0FC8D0 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.eurekalert.org/pub_releases/2006-01/tmsh-rot012406.php Role of the nervous system in regulating stem cells = discovered

Public = release date:=20 26-Jan-2006
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Contact: Mount Sinai Press Office
newsmedia@mssm.edu
212-241-9200=
The Mount Sinai = Hospital /=20 Mount Sinai School of Medicine

Role of the nervous system in regulating stem cells=20 discovered

Study led by Mount Sinai School of Medicine may = provide new=20 hope for cancer patients and others with compromised immune = systems

New=20 study by Mount Sinai researchers may lead to improved stem cell = therapies for=20 patients with compromised immune systems due to intensive cancer therapy = or=20 autoimmune disease. The study is published in this week's issue of Cell. =

A group, led by Paul Frenette, Associate Professor of Medicine at = Mount Sinai=20 School of Medicine, found that the sympathetic--or "fight or flight" = branch--of=20 the nervous system plays a critical role in coaxing bone marrow stem = cells into=20 the bloodstream. Bone marrow cells known as hematopoietic stem cells are = the=20 source for blood and immune cells.=20

Hematopoietic stem cell transplants are now routinely used to restore = the=20 immune systems of patients after intensive cancer therapy and for = treatment of=20 other disorders of the blood and immune system, according to the = National=20 Institutes of Health. While physicians once retrieved the stem cells = directly=20 from bone marrow, doctors now prefer to harvest donor cells that have = been=20 mobilized into circulating blood.=20

In normal individuals, the continuous trafficking of the stem cells = between=20 the bone marrow and blood fills empty or damaged niches and contributes = to the=20 maintenance of normal blood cell formation, according to the = researchers.=20 Although it has been known for many years that the mobilization of = hematopoietic=20 stem cells can be enhanced by multiple chemicals, the mechanisms that = regulate=20 this critical process are largely unknown, they said.=20

One factor in particular, known as hematopoietic cytokine = granulocyte-colony=20 stimulating factor (G-CSF), is widely used clinically to elicit = hematopoietic=20 stem cell mobilization for life-saving bone marrow transplantation, said = Dr.=20 Frenette.=20

Several years ago, Dr. Frenette's group reported that a second = compound,=20 fucoidan, which is synthesized by certain seaweeds, could also spur the = stem=20 cells into action. The group speculated that the seaweed derivative = might work=20 by imitating a similar compound, called sulfatide, naturally present in=20 mammalian tissues.=20

To test the idea, the researchers examined mice lacking the enzyme=20 responsible for making sulfatide.=20

"Lo and behold, mice lacking the enzyme Cgt did not mobilize = hematopoietic=20 stem cells at all when treated with the stimulating factor G-CSF or = fucoidan,"=20 Dr. Frenette said. "You don't get such dramatic results that often in = science.=20 We knew we had stumbled onto something important."=20

To their surprise, further study failed to connect the stalled stem = cell=20 movement to sulfatide. Rather, they found, the deficiency stemmed from a = defect=20 in the transmission of signals sent via the sympathetic nervous system. = The=20 products of Cgt contribute to the myelin sheath that coats and protects = nerve=20 cells, they explained.=20

Mice with other nervous system defects also exhibited a failure to = mobilize=20 bone marrow stem cells, they found. Moreover, drugs that stimulate the=20 sympathetic nervous system restored stem cell movement into the blood = stream in=20 mice with an impaired ability to respond to norepinephrine, the = signature=20 chemical messenger of the sympathetic system.=20

"The nervous system plays an important role in producing signals that = maintain the stem cell niche and retention in bone marrow," Dr. Frenette = said.=20

"The new findings add another dimension of complexity to the = processes=20 involved in stem cell maintenance and mobilization and emphasize the=20 interrelationships among the nervous, skeletal and hematopoietic = systems," he=20 added. "They all have to work together =96 to talk to each other =96 to = produce=20 blood and maintain stem cells."=20

The results suggest that differences in the sympathetic nervous = systems of=20 stem cell donors may explain "conspicuous variability" in the efficiency = with=20 which they mobilize hematopoietic cells into the bloodstream, the = researchers=20 said. Furthermore, drugs that alter the signals transmitted by the = sympathetic=20 nervous system to the stem cells in bone may offer a novel strategy to = improve=20 stem cell harvests for stem cell-based therapeutics, they added.=20

The unexpected findings by Frenette and his colleagues further = "suggest that=20 the pharmacological manipulation of the sympathetic nervous system may = be a=20 means of therapeutically targeting the stem cells in their niche for the = purpose=20 of either mobilization or, conversely, attracting stem cells to the = niche=20 following transplantation," they added.=20

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