The Scientist : NewsBlog Print: Stem cells emerge at night
The Scientist: NewsBlog:
Stem cells emerge at night
Posted by Edyta Zielinska
[Entry posted at 8th October 2008 05:47 PM GMT]

Stem cells undergo circadian cycles in humans, emerging from the bone marrow into the bloodstream at higher concentrations at night than in the day, according to a report in Cell Stem Cell this week. The study suggests that a simple change in hospital procedures could significantly increase stem cell yield for therapy.

"We can take advantage of [the findings] if we coordinate our clinical practices" to harvest stem cells for cancer patients late in the day, said author Paul Frenette, a clinical researcher at Mount Sinai School of Medicine.

The work is an update on a paper published online in February by the same group in Nature. In that study, Frenette and his colleagues showed that haematopoietic stem cells (HSCs) leave their niche in mouse bone marrow and travel through the blood during the day -- the mouse's time of rest. A cytokine called CXCL12 expressed by stromal cells in the bone marrow niche signals their movement; when CXCL12 levels go down, HSCs escape into the blood. When the levels increase, the cells return.

HSCs are commonly used to replenish a patient's stem cells which are depleted during cancer thereapy. To determine whether these findings might be meaningful in clinical application, Frenette's group followed up with the current study, in which they examined stem cell cycles in humans. The researchers compared two time-points for HSC harvesting, one at 8am and one at 8pm in normal subjects, and saw a significant increase in HSC levels in the evening harvest.

In practice, patients being treated with autologous HSCs over the course of cancer therapy are first treated with a drug, G-CSF, that forces the stem cells into the blood; the cells are then harvested with plasmapharesis. Frenette's group wanted to know "whether these physiological cycles are maintained? when you force the mobilization with drugs," he told The Scientist. So the researchers compared the number of stem cells they were able to extract from cancer patients who underwent the procedure before 12:30 pm, to those that underwent the procedure before 3:30 pm. Even such a short time period made a difference -- they observed a significant increase in harvest at the later time point.

Current practice in the clinic is to harvest stem cells in the morning, said Frenette, but moving the procedure to afternoon or evening could mean fewer plasmapheresis sessions for patients. It is unclear why the stem cells leave their niche during a patient's time of rest; Frenette speculates that "there might be some function in repair and regeneration," but added that those associations are hard to prove.


 

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A Darwinian religion?
by Robert Pytlik

[Comment posted 2008-10-11 10:26:25]
I think null null?s comment not only oversimplifies the issue but does not bring any evidence for his (her?) statement. The referrences do not address the topic but the personal views and beliefs of the blogger. I suppose this kind of argument would be perhaps appropriate in a religious debate, but not on a scientific blog.



Most effective time for chemotherapy iinfusion
by Ken Dev

[Comment posted 2008-10-11 09:56:30]
There has been a lot of research on the circidian rhythm and cancer treatment-- at least for some tumors. It has been found, e.g., that very early morning treatment is more effective with the same chemo regimen with far less toxicity than given at the standard time. However, don't expect the oncology nurses to be around to treat patients at unreasonable hours, kind though they are!

The question is: Has this any correlation with more production of stem cells at night? I'd be interested to hear since I am professionally interested in cancer therapeutics.

Readers interested in circidian rhythm and tumors should look up the following papers:


Circadian rhythm-modulated chemotherapy with high dose 5-fluorouracil against gastrointestinal cancers: evaluation and case report. Nagoya J Med Sci,Vol.62, 29-38 (1999)

Fu L, Lee CC. The Circadian Clock: Pacemaker and Tumour Suppressor. Nature, Reviews 2003; 3: 350-61.



Emerge at Night? - Response
by Edyta Zielinska

[Comment posted 2008-10-10 14:18:19]
Thank you for your question, David Eve. The results of this group?s earlier research in mice showed that more HSCs emerge during the day ? a time of rest for mice. They followed this study up by looking at two time points in healthy humans, one in the morning and one in the evening, and found more stem cells in evening harvest ? closer to a human?s time of rest. We can?t tell, from this study, exactly at what point the HSCs begin to shift to the blood and when they shift back to the bone marrow. But we can say that the levels are higher later in the day and in the evening.



Emerge at Night?
by DAVID EVE

[Comment posted 2008-10-10 13:17:05]
Maybe I'm misunderstanding this post, but doesn't it show the opposite? if you can get more cells at 8pm and 3.30pm compared with 8am and 12.30 pm respectively, doesn't this mean more cells emerge during the day, particularly since they recommend extracting cells during the afternoon rather than the morning? Nevertheless a circadian rhythm is certainly of great interest, even if it does seem the wrong way round to me.



SC displaced more easily when off-duty
by null null

[Comment posted 2008-10-10 01:48:16]
"it is unclear why the stem cells leave their niche during a patient's time of rest"


SC are more easily displaced during the organism's rest time simply because their genome is off-duty then, part of its duty is to be on-call at the specific site where it is:


Life's Chirality And Circadian Rhythm,
Evidence Of Updated Darwinian Evolution


A. Updated life's concepts:

LINK

- Earth life consists of three strata: genes are primal organisms, genomes are evolved 2nd
stratum organisms, and cellular organisms are evolved 3rd stratum.

- Life's evolution started at genesis.

- Life's evolution is not random. It is biased, driven by culture.


B. Earliest evidences of updated Darwinian evolution:

- Life's chirality
LINK
LINK

- Circadian rhythm

LINK


Suggesting,

Dov Henis
LINK



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