Regenerative Chemical Turns Muscle Cells Into Stem Cells ... (Reversine)

[Murray Charters <mcharters@xxxxxxxxxxxxxx>]

Regenerative Chemical Turns Muscle Cells Into Stem Cells ... (Reversine)
Source:  Scripps Research Institute

Date:  2003-12-25

A group of researchers from The Scripps Research Institute has identified a 
small synthetic molecule that can induce a
cell to undergo dedifferentiation--to move backwards developmentally from its 
current state to form its own precursor
cell.

This compound, named reversine, causes cells which are normally programmed to 
form muscles to undergo reverse
differentiation--retreat along their differentiation pathway and turn into 
precursor cells.

These precursor cells are multipotent; that is, they have the potential to 
become different cell types. Thus, reversine
represents a potentially useful tool for generating unlimited supply of such 
precursors, which subsequently can be
converted to other cell types, such as bone or cartilage.

"This [type of approach] has the potential to make stem cell research more 
practical," says Sheng Ding, Ph.D. "This
will allow you to derive stem-like cells from your own mature cells, avoiding 
the technical and ethical issues
associated with embryonic stem cells."

Ding, who is an assistant professor in the chemistry department at Scripps 
Research conducted the study--to be
published in an upcoming issue of the Journal of the American Chemical 
Society--with Peter G. Schultz, Ph.D., who is a
professor of chemistry and Scripps Family Chair of Scripps Research's Skaggs 
Institute of Chemical Biology, and their
colleagues.

Regenerative Medicine and Stem Cell Therapy

Stem cells have huge potential in medicine because they have the ability to 
differentiate into many different cell
types--potentially providing doctors with the ability to produce cells that 
have been permanently lost by a patient.

For instance, the damage of neurodegenerative diseases like Parkinson's, in 
which dopaminergic neurons in the brain are
lost, may be ameliorated by regenerating neurons. Another example of a 
potential medical application is Type 1
diabetes, an autoimmune condition in which pancreatic islet cells are destroyed 
by the body's immune system. Because
stem cells have the power to differentiate into islet cells, stem cell therapy 
could potentially cure this chronic
condition.

However bright this promise, many barriers must be overcome before stem cells 
can be used in medicine. Stem cell
therapy would be most effective if you could use your own stem cells, since 
using one's own cells would avoid potential
complications from immune rejection of foreign cells. However, in general it 
has proven very difficult to isolate and
propagate stem cells from adults. Embryonic stem cells (ESCs) offer an 
alternative, but face both practical and ethical
hurdles associated with the source of cells as well as methods for controlling 
the differentiation of ESCs. A third
approach is to use one's own specialized cells and dedifferentiate them.

Normally, cells develop along a pathway of increasing specialization. Muscles, 
for instance, develop after embryonic
stem cells develop into "mesenchymal" progenitor cells, which then develop into 
"myogenic" cells. These muscle cells
fuse and form the fibrous bundles we know as muscles.

In humans and other mammals, these developmental events are irreversible, and 
in this sense, cell development resembles
a family tree. One wouldn't expect a muscle cell to develop into a progenitor 
cell any more than one would expect a
woman to give birth to her own mother.

However, such phenomena do happen in nature from time to time.

Some amphibians have the ability to regenerate body parts that are severed by 
using dedifferentiation. When the unlucky
amphibian loses a limb or its tail, the cells at the site of the wound will 
undergo dedifferentiation and form
progenitor cells, which will then multiply and redifferentiate into specialized 
cells as they form an identical
replacement to the missing limb or tail. In humans, the liver is unique in its 
regenerative capacity, possibly also
involving dedifferentiation mechanism.

The Scripps Research scientists hope to find ways of mimicking this natural 
regeneration by finding chemicals that will
allow them to develop efficient dedifferentiation processes whereby healthy, 
abundant, and easily accessible adult
cells could be used to generate stem-like precursor cells, from which they 
could make different types of functional
cells for repair of damaged tissues. Reversine is one of the first steps in 
this process.

However, tissue regeneration is years away at best, and at the moment, Schultz 
and Ding are still working on
understanding the exact biochemical mechanism whereby reversine causes the 
muscle cells to dedifferentiate into their
progenitors, as well as attempting to improve the efficiency of the process. 
"This [type of research] may ultimately
facilitate development of small molecule therapeutics for stimulating the 
body's own regeneration," says Ding. "They
are the future regenerative medicine."

###

The article, "Dedifferentiation of Lineage-Committed Cells by a Small Molecule" 
is authored by Shuibing Chen, Qisheng
Zhang, Xu Wu, Peter G. Schultz, and Sheng Ding and is available to online 
subscribers of the Journal of the American
Chemical Society at: 
 . The 
article will also be
published in an upcoming issue of JACS.

This work was supported by The Skaggs Institute for Research and the Novartis 
Research Foundation.

This story has been adapted from a news release issued by Scripps Research 
Institute.

SOURCE: Scripps Research Institute / ScienceDaily Magazine


Reference:

Chemical Turns Stem Cells Into Neurons Say Scientists At Scripps Research 
Institute


New Stem Cell Maintenance Protein Found


Stem Cells Shown To Regenerate Damaged Lung Tissue For First Time


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