I got hopeful with this article in the N.Y. Times and decided to share
with you :
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June 20, 2000
New Alchemy: Bone and Cartilage From a
Snippet of Skin
By GREG WINTER
Taking a less traveled path in the quest
to replace damaged organs with parts
grown in the laboratory, a professor at the
University of California at San Francisco
reports that he has changed human skin and
gum cells into bone and cartilage.
"Sounds like science fiction, doesn't it?" said
the researcher, Dr. Rajendra Bhatnagar, who
is head of the university's graduate
bioengineering group.
"But that's what we do."
Dr. Bhatnagar's findings, detailed in the latest
issue of Cells and Materials, a peer-reviewed
journal, provides one of the first alternatives
to researchers' widespread reliance on stem
cells, the primordial cells from which all
others emerge.
For several decades, researchers have tried
to find a source of living cells to coax into
new tissues. Most are focusing on stem cells,
because, in theory, they can be manipulated
to form any organ in the body.
But they are difficult to harvest. Stem cells
are found in bone marrow, but make up only
one out of every 10,000 cells, or even fewer as patients age,
making
them extremely difficult, not to mention painful, to excavate
and isolate
through biopsies and other means.
Human embryos offer another source of stem cells, but the
prospect of
mining biological matter from fetuses has raised objections.
In 1994,
President Clinton banned the use of money from the National
Institutes of
Health for experiments that either create or destroy embryos,
a policy
Congress later adopted.
Using embryonic stem cells also has immunological
complications. Just as
the body rejects transplanted organs from donors, it can
reject tissues
grown from donated cells.
Skin, however, is not only the largest organ in the body,
providing
researchers with a seemingly unlimited number of cells, but it
is also the
most accessible. Within the dermis, the middle layer in the
folds of human
skin, are fibroblasts, the cells that Dr. Bhatnagar and his
researchers
convert into bone and cartilage. So it is with gums as well,
where
fibroblasts are plentiful and, Dr. Bhatnagar reports, equally
pliable.
From a snippet of skin or gum tissue no more than a few cubic
millimeters in volume, Dr. Bhatnagar says he can generate
enough tissue
to fill a hole in bone or cartilage many hundreds of times
that size.
And because the fibroblasts come directly from the donor,
there is no
risk of rejection.
"This will have enormous impact in the field," said Dr.
Antonios Mikos,
vice president of the Tissue Engineering Society and editor of
Tissue
Engineering, which published a paper by Dr. Bhatnagar last
year on
converting a type of fibroblast found in gums into bone.
"There are many
technologies trying to isolate stem cells from bone.
The problems of those technologies may be solved if one can
use dermal
fibroblasts."
Dr. Bhatnagar's newest paper describes the transformation of a
different
type of gum cell, the gingival fibroblast, into bone.
In November, CeraMed Dental, a small company owned primarily
by
Dentsply International, got approval from the Food and Drug
Administration to sell a product based on Dr. Bhatnagar's
research for
patients with advanced periodontal disease. CeraMed paid the
university
for the rights to use the research; Dr. Bhatnagar says he has
no financial
interest in the company.
Inserted wherever teeth have eroded, CeraMed's product, Pepgen
P-15,
works by transforming fibroblasts in the gums into bone,
CeraMed
officials say.
In clinical trials required for F.D.A. approval, the product
proved 38
percent more effective than current methods of plugging holes
in teeth,
and generated new growth over roughly three-fourths of
deteriorated
areas.
In one test, a middle-aged man whose jaw had become too
dilapidated
to bear false teeth had his gums packed with the pasty
substance.
After six months, he had grown what amounted to a new jaw,
somewhat
crudely formed, but solid enough to withstand drilling and
support fake,
screw-in teeth.
Dr. Bhatnagar hopes the technology can be adapted to eliminate
the need
for costly operations for other degenerative diseases.
Osteoarthritis, characterized by a breakdown in the joint's
cartilage, is the
principle cause of nearly half a million knee and hip
replacements each
year, according to the American Association of Orthopedic
Surgeons.
Of course, fibroblasts are not supposed to turn into bone or
cartilage.
Biologists have long believed that cells do not change course
once they
fully differentiate.
But Dr. Bhatnagar pays them no mind. After spending more than
40
years tinkering with the laws of nature, he has learned to be
irreverent.
"There is no dogma that has any true basis," he is fond of
saying.
His skeptics disagree.
Dr. Arnold Kaplan, a founder of Osiris Therapeutics and one of
the first
scientists to isolate the stem cells found in bone marrow,
said he was not
familiar with Dr. Bhatnagar's work but speculated that the
professor was
unknowingly experimenting with another type of stem cell,
called a
pericyte, which also inhabits blood-rich tissues like skin and
gums.
Pericytes, virtually indistinguishable from fibroblasts, are
as flexible as
their counterparts within bone marrow, and may explain how Dr.
Bhatnagar's findings seemingly throw the developmental process
into
reverse. "We don't know that you can take one type of tissue
cell and get
it to back up," Dr. Kaplan said.
"In the cases that have been looked at with some rigor, that
isn't how it
happens."
But Dr. Bhatnagar said his years of experimenting left him
certain that it
was the fibroblasts that were changing their properties, and
as he
publishes more findings he is convincing a growing number of
his peers.
His work with fibroblasts began in the late 1980's. Dr.
Bhatnagar sent his
graduate students to the university's medical clinic, where
they collected
the discarded foreskins of just-circumcised babies. Then he
extracted the
fibroblasts and placed them on a matrix that closely mimicked
the
properties of bone.
Surrounded by minerals, held fast by P-15, a string of sticky
amino acids
that allowed them to interact, the skin cells conformed to the
new
environment as if they always belonged there. Within three
weeks, the
cells began producing proteins found only in bone. The same
was done
with more fibroblasts, this time from gum tissue, with the
same results.
Then the researchers packed fibroblasts tightly together and
deprived
them of oxygen, imitating the conditions of cartilage.
Once again, the cells responded, as if they knew the lines of
different
characters and delivered them as soon as the set was changed.
"They
completely forgot how to be skin cells," said Dr. Bhatnagar.
"We played mind games with the cells.
We made them think of home."
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Cheers,
Joao Paulo - Salvador,BA,Brazil
