DEXTER C. CORRALES, RN, RM

September 9, 2013

Stem Cell Treatments Overtake ScienceBy LAURA BEIL

TIJUANA, Mexico — Maggie Alejos arrived here in June

from St. Anne, Ill., with her husband, her daughter and a

cashier’s check for $13,500, payable to the Regenerative

Medicine Institute.

Rail-thin, with an oxygen tube anchored above her upper

lip, Ms. Alejos, a retired Army nurse, has coped

with emphysema for a dozen of her 65 years. Once she

came close enough to a lung transplant that doctors

prepared her for surgery, only to discover that the donor

lung was unfit.

At a hospital here, doctors affiliated with the institute

extracted about seven ounces of fat from her thighs,

hoping to harvest about 130 million stem cells and implant

them in her failing lungs.

Across the Internet — where Ms. Alejos learned about the

Tijuana institute — adult stem cells are promoted as a cure

for everything from sagging skin to severed spinal cords.

On the surface, the claim is plausible. Scientists have

discovered that fat, bone marrow and other parts of the

body contain stem cells, immature cells that can rejuvenate

themselves, at least in the tissue they are naturally found.

But it has yet to be proved that these cells can regenerate

no matter where they are placed, or under what conditions

this might occur. Moreover, questions about safety remain

unanswered.

These sober realities do not appear to have slowed the rise

of an international industry catering to customers who may

pay tens of thousands of dollars in cash for their shot at a

personal miracle. (Some foreign operators offer creative

variations on the theme, like cells from sharks and sheep.)

Domestic providers, too, can push the limits. In July, for

example, a former pathologist at the Medical University of

South Carolina pleaded guilty to illegally processing and

shipping stem cells for treatment without approval from the

university or the Food and Drug Administration.

The number of clinics and products has reached the point

that scientists fear repercussions for their own work. Dr.

Hesham Sadek of the University of Texas Southwestern

Medical Center in Dallas, who is studying heart muscle

regeneration, worries that the marketing deluge now makes

it hard for patients to tell science from swindle, and all that

lies on the spectrum in between.

“It really has the potential to undermine the legitimacy of

the whole field,” he said.

Trial or Treatment?

Even though Tijuana has perhaps 20 clinics offering adult

stem cell therapy, Dr. Javier Lopez, founder of

the Regenerative Medicine Institute, says it is his that has

become “the poster company to knock down.”

Born and educated in Tijuana, he has lived and worked

across the border, in San Diego, for more than 30 years,

mainly as a health care administrator. He became inspired

by stem cells after accompanying a physician friend to a

conference in Palm Springs, Calif., in 2008.

“It was eye-opening,” he said. “I immediately thought, ‘This

is the future of medicine, and I want to be a part of it.’ ”

He says he runs the institute within the accepted

framework of clinical trials: Patients sign consent forms

acknowledging that the treatment is experimental. Studies

are registered with the National Library of Medicine in the

United States.

Being accepted for treatment requires more than cash.

Protocols and procedures are approved by the institutional

review board, or I.R.B., at Hospital Angeles Tijuana, and

are administered by physicians at the hospital. “The focus

of our trial, from Day 1, has been safety,” Dr. Lopez said.

Still, skeptics in the United States are not convinced. Leigh

Turner, a bioethicist at the University of Minnesota, says

the Regenerative Medicine Institute blurs the boundary

between trial and treatment.

The institute’s patient consent form “would not pass muster

with a competent American I.R.B.,” Dr. Turner said, and the

testimonials on its Web site place the emphasis squarely

on results.

Moreover, studying patients who pay undermines the trials’

scientific validity, Dr. Turner said. The patient sample is

skewed toward those with the means to travel, and their

financial investment may amplify an already strong placebo

effect.

Dr. Lopez says that scientists in Mexico lack the

government research support available in the United

States, leaving establishments like his no choice but to

charge patients.

He agrees that many stem cell providers are dubious, and

says he works with the Mexican authorities to try to

establish uniform standards. As for his own institute, he

said, “I’m very proud of what we are doing,” and added, “I

get upset when people start talking trash about what is

done south of the border.”

A Gray Area

In the United States, too, it is easy to conduct business

outside government oversight, said Dr. George Q. Daley,

who studies stem cells for blood diseases at Harvard

Medical School. Close down one shady operation, he went

on, and more seem to randomly pop up.

Even questionable publicity does not necessarily hurt

business. Regnocyte, a company in Florida, posted an

unflattering CNN report about iton its Web site under the

heading “special coverage.”

If the stem cell business continues to flourish without

proper scrutiny, Dr. Daley and others fear research

progress will suffer. Clinical trials depend on patients who

are willing to sign on even though they know they might be

given a placebo, while competing clinics are offering what

seems to be a sure thing. In addition, patients who have

already had stem cell therapy could be ineligible for trials.

And if too many patients try stem cells unsuccessfully, the

public may come to see the entire field as a failure, said Dr.

Sadek, the heart cell scientist in Dallas. Many comments

on articles about his last paper, published in the journal

Nature, “were skeptical and jaded,” he continued. “One

said, ‘I’ve gotten stem cell therapy and nothing happened.’

If the public loses faith in regenerative medicine in general,

funding can be affected.”

A Lack of Data

Beyond the online testimonials, there is little evidence to

indicate whether adult stem cell treatments on offer are

working. Paul Knoepfler, a stem cell researcher at the

University of California, Davis, says the lack of data is

vexing.

“There is absolutely no legitimate reason for such clinics to

be not publishing their data,” he wrote on his stem cell

blog this year. “Yet they almost never do it.”Stem cell

businesses say they have other priorities. “I’m not that

interested in doing a lot of research for publication

purposes only,” said Maynard A. Howe, the chief executive

of Stemedica Cell Technologies in San Diego, which is

developing a drug made from donated stem cells. Dr.

Howe and his brother Roger started the company in 2005

after a sister-in-law received stem cells in Russia for

a spinal cord injury.

Dr. Howe says that his company publishes just enough

data to meet F.D.A. requirements, but that he would rather

his scientists spend their time getting a product to market.

He also defends the practice of foreign trials largely on

economic grounds. Outside the United States, he said, “I

can do a PET scan for $500,” a fraction of the typical

American rate. “Why wouldn’t I do my clinical trial

overseas?”

For his part, Dr. Lopez says he is trying to publish data

from the 125 patients he has treated so far, but he faces a

struggle. “Nobody wants to talk to us because we are from

Tijuana,” he said of medical journals. He has managed to

get just a case description accepted for publication.

So for now, he does not have much to show in the way of

science. He believes in stem cells — and in that, he and

his critics share common ground. The challenge for

scientists is to promote the promise of stem cells with both

excitement and restraint. It can be a hard line to walk.

“I understand how difficult it is — how many years and

sometimes decades it takes before you discover a new

therapy,” said Dr. Daley, of Harvard. “We have a

tremendous enthusiasm about the potential of stem cell

therapy.

“That said, these aren’t magical agents that run around

your body and fix things. It’s frustrating to watch other

people who, even well intentioned, aren’t acting in their

patients’ best interest.”

This week, the International Society for Stem Cell

Research is to release a statement declaring the use of

stem cells outside scientific settings to be “a threat to

patient welfare, patient autonomy and to the scientific

process,” according to its public policy chairman, Jonathan

Kimmelman, a bioethicist at McGill.

This is the same group that once tried to offer an online

guide to stem cell clinics, but the journal Nature

reported that the effort was abruptly abandoned under

threat of lawsuits.

Acute Pancreatitis Overview

Acute pancreatitis is sudden swelling and inflammation of the pancreas.

CAUSES

The pancreas is an organ located behind the stomach that produces chemicals called enzymes, as well as the hormones insulin and glucagon. Most of the time, the enzymes are only active after they reach the small intestine, where they are needed to digest food.

When these enzymes somehow become active inside the pancreas, they eat (and digest) the tissue of the pancreas. This causes swelling, bleeding (hemorrhage), and damage to the pancreas and its blood vessels.

Acute pancreatitis affects men more often than women. Certain diseases, surgeries, and habits make you more likely to develop this condition.

The condition is most often caused by alcoholism and alcohol abuse (70% of cases in the United States). Genetics may be a factor in some cases. Sometimes the cause is not known, however.

Other conditions that have been linked to pancreatitis are:

Autoimmune problems (when the immune system attacks the body)

Blockage of the pancreatic duct or common bile duct, the tubes that drain enzymes from the pancreas

Damage to the ducts or pancreas during surgery High blood levels of a fat called triglycerides

(hypertriglyceridemia) Injury to the pancreas from an accident

Other causes include:

Complications of cystic fibrosis Hemolytic uremic syndrome Hyperparathyroidism Kawasaki disease Reye syndrome Use of certain medications (especially estrogens,

corticosteroids, thiazide diuretics, and azathioprine) Viral infections, including mumps, coxsackie

B, mycoplasma pneumonia, and campylobacter

SYMPTOMS

The main symptom of pancreatitis is abdominal pain felt in the upper left side or middle of the abdomen.

The pain:

May be worse within minutes after eating or drinking at first, especially if foods have a high fat content

Becomes constant and more severe, lasting for several days

May be worse when lying flat on the back May spread (radiate) to the back or below the left shoulder

blade

People with acute pancreatitis often look ill and have a fever, nausea, vomiting, and sweating.

Other symptoms that may occur with this disease include:

Clay-colored stools Gaseous abdominal fullness Hiccups Indigestion Mild yellowing of the skin and whites of the eyes (jaundice) Skin rash or sore (lesion) Swollen abdomen

EXAMS AND TESTS

The doctor will perform a physical exam, which may show that you have:

Abdominal tenderness or lump (mass) Fever Low blood pressure Rapid heart rate Rapid breathing (respiratory) rate

Laboratory tests will be done. Tests that show the release of pancreatic enzymes include:

Increased blood amylase level Increased serum blood lipase level Increase urine amylase level

Other blood tests that can help diagnose pancreatitis or its complications include:

Complete blood count (CBC) Comprehensive metabolic panel

Imaging tests that can show inflammation of the pancreas include:

Abdominal CT scan Abdominal MRI Abdominal ultrasound

TREATMENT

Treatment often requires a stay in the hospital and may involve:

Pain medicines Fluids given through a vein (IV) Stopping food or fluid by mouth to limit the activity of the

pancreas

Occasionally a tube will be inserted through the nose or mouth to remove the contents of the stomach (nasogastric suctioning). This may be done if vomiting or severe pain do not improve, or if a paralyzed bowel (paralytic ileus) develops. The tube will stay in for 1 - 2 days to 1 - 2 weeks.

Treating the condition that caused the problem can prevent repeated attacks.

In some cases, therapy is needed to:

Drain fluid that has collected in or around the pancreas Remove gallstones Relieve blockages of the pancreatic duct

In the most severe cases, surgery is needed to remove dead or infected pancreatic tissue.

Avoid smoking, alcoholic drinks, and fatty foods after the attack has improved.

OUTLOOK (PROGNOSIS)

Most cases go away in a week. However, some cases develop into a life-threatening illness.

The death rate is high with:

Hemorrhagic pancreatitis Liver, heart, or kidney impairment Necrotizing pancreatitis

Pancreatitis can return. The likelihood of it returning depends on the cause, and how successfully it can be treated.

POSSIBLE COMPLICATIONS Acute kidney failure Acute respiratory distress syndrome (ARDS) Buildup of fluid in the abdomen (ascites) Cysts or abscesses in the pancreas Heart failure Low blood pressure

Repeat episodes of acute pancreatitis can lead to chronic pancreatitis.

WHEN TO CONTACT A MEDICAL PROFESSIONAL

Call your health care provider if:

You have intense, constant abdominal pain You develop other symptoms of acute pancreatitis

PREVENTION

You may lower your risk of new or repeat episodes of pancreatitis by taking steps to prevent the medical conditions that can lead to the disease:

Avoid aspirin when treating a fever in children, especially if they may have a viral illness, to reduce the risk of Reye syndrome.

Do NOT drink too much alcohol. Make sure children receive vaccines to protect them

against mumps and other childhood illnesses (see: Immunizations - general overview).

REFERENCES

Banks PA, Freeman ML; Practice Parameters Committee of the American College of Gastroenterology. Practice guidelines in acute pancreatitis. Am J Gastroenterol . 2006;101:2379-2400.

Frossard JL, Steer ML, Pastor CM. Acute pancreatitis. Lancet . 2008;371:143-152.

Owyang C. Pancreatitis. In: Goldman L, Ausiello D, eds. Cecil Medicine . 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 147.