(weird) NYT story about turning skin into bone and cartilage.
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."
Copyright 2000 The New York Times Company |
