In SCIENCE & STEM CELLS on November 21, 2012 at 7:44 am

B0007671 Mouse embryonic stem cells

Pluripotent stem cells are potentially an invaluable therapeutic resource, as shown in a recent study conducted by the Stanford University School of Medicine.  Within this study, researchers found that with appropriate initial coaching of cells and through the use of environmental cues, the human body has the ability to direct differentiation of cells.


Pluripotent stem cells are nature’s double-edged sword. Because they can develop into a dizzying variety of cell types and tissues, they are a potentially invaluable therapeutic resource. However, that same developmental flexibility can lead to dangerous tumors called teratomas if the stem cells begin to differentiate out of control in the body.

To prevent this outcome, researchers must first give the cells a not-so-subtle shove toward their final developmental fate before transplanting them into laboratory animals or humans. But exactly how to do so can vary widely among laboratories. Now researchers at the Stanford University School of Medicine have used an experiment in mice to hit upon a way to possibly skip this fiddly step by instead relying mostly on signals within the body to keep the stem cells in line.

“Before we can use these cells, we have to differentiate, or ‘coach,’ them down a specific developmental pathway,” said Michael Longaker, MD, the Deane P. and Louise Mitchell Professor in the School of Medicine. “But there’s always a question as to exactly how to do that, and how many developmental doors we have to close before we can use the cells. In this study, we found that, with appropriate environmental cues, we could let the body do the work.”

Allowing the body to direct differentiation could speed the U.S. Food and Drug Administration’s approval of using such pluripotent stem cells, Longaker believes, by eliminating the extended periods of laboratory manipulation required during the forced differentiation of the cells.

Longaker, who co-directs Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, is the senior author of the research, published online Nov. 19 in the Proceedings of the National Academy of Sciences. Postdoctoral scholars Benjamin Levi, MD, and Jeong Hyun, MD, and research assistant Daniel Montoro are co-first authors of the work. Longaker is also a member of the Stanford Cancer Institute.

“Once we identify the key proteins and signals coaching the tissue within the body, we can try to mimic them when we use the stem cells,” said Longaker. “Just as the shape of water is determined by its container, cells respond to external cues. For example, in the future, if you want to replace a failing liver, you could put the cells in a scaffold or microenvironment that strongly promotes liver cell differentiation and place the cell-seeded scaffold into the liver to let them differentiate in the optimal macroenvironment


Groundbreaking New Understanding of Stem Cells: Findings May Improve Ability to Manipulate Cell Fate and Promote Healing | www.sciencemagnews.com

In SCIENCE & STEM CELLS on May 21, 2010 at 5:52 pm

Groundbreaking New Understanding of Stem Cells: Findings May Improve Ability to Manipulate Cell Fate and Promote Healing

The study, led by Scripps Research Associate Professor Sheng Ding and Senior Director of the Scripps Research Center for Mass Spectrometry Gary Siuzdak, was published in an advance, online edition of the journal Nature Chemical Biology on May 2, 2010.

In the research, the team used a unique approach to better understand stem cells, which have the ability to change or “differentiate” into adult cell types such as hair cells, skin cells, nerve cells. Understanding how stem cells mature opens the door for scientists and physicians to manipulate the process to meet the needs of patients, potentially treating such intractable conditions as Parkinson’s disease and spinal injury.”In the past, scientists trying to understand stem cell biology focused on genes and proteins,” said Ding. “In our study, we looked at stem cell regulation in a different way — on the biochemical level, on a functional level. With metabolomics profiling, we were able to look at naturally occurring small molecules and how they control cell fate on a completely different level.”The new paper describes parts of the stem cell “metabolome” — the complete set of substances “metabolites” formed in metabolism, including all naturally occurring small molecules, biofluids, and tissues. The scientists then compared this profile to those of more mature cells, specifically of nerve cells and heart cells.When the results were tallied, the scientists had found about 60 previously unidentified metabolites associated with the progression of stem cells to mature cells, as well as an unexpected pattern in the chemistry that mirrored the cells’ increasing biological maturity.

via Groundbreaking New Understanding of Stem Cells: Findings May Improve Ability to Manipulate Cell Fate and Promote Healing | www.sciencemagnews.com.


In SCIENCE & STEM CELLS on October 8, 2009 at 5:10 pm

stem cell - skin cells

In normal skin (left), the stem cells at the base, shown in green, differentiate into skin cells, shown in red. In mice whose skin has neither C/EBP-beta nor C/EBP-beta (middle), this differentiation is blocked: green-labeled stem cells appear in upper layers of skin, and there are no differentiated skin cells (no red staining). This also happens at the initial stages of basal cell carcinomas. In skin where C/EBP-beta is present but has lost its capacity to interact with E2F, a molecule that regulates the cell cycle (right), skin cells start differentiating abnormally, before they have properly exited the stem cell “program” (yellow/orange). This is similar to what is observed in the initial stages of squamous cell carcinomas, a more aggressive and invasive skin tumor

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