Adipose – Derived Stem Cell Therapy Research
In 2001, researchers at the University of California, Los Angeles, described the isolation of a new population of adult stem cells from liposuctioned adipose tissue. These stem cells, now known as adipose-derived stem cells or ADSCs, have gone on to become one of the most popular adult stem cells populations in the fields of stem cell research and regenerative medicine. As of today, thousands of research and clinical articles have been published using ASCs, describing their possible pluripotency in vitro, their uses in regenerative animal models, and their application to the clinic. This paper outlines the progress made in the ASC field since their initial description in 2001, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo, their use in mediating inflammation and vascularization during tissue regeneration, and their potential for reprogramming into induced pluripotent cells. Read full peer reviewed article
Stem cells from fat outperform those from bone marrow in fighting disease
Durham, NC — A new study appearing in the current issue of STEM CELLS Translational Medicine indicates that stem cells harvested from fat (adipose) are more potent than those collected from bone marrow in helping to modulate the body’s immune system. The finding could have significant implications in developing new stem-cell-based therapies, as adipose tissue-derived stem cells (AT-SCs) are far more plentiful in the body than those found in bone marrow and can be collected from waste material from liposuction procedures. Stem cells are considered potential therapies for a range of conditions, from enhancing skin graft survival to treating inflammatory bowel disease. Researchers at the Leiden University Medical Center’s Department of Immunohematology and Blood Transfusion in Leiden, The Netherlands, led by Helene Roelofs, Ph.D., conducted the study. They were seeking an alternative to bone marrow for stem cell therapies because of the low number of stem cells available in marrow and also because harvesting them involves an invasive procedure. “Adipose tissue is an interesting alternative since it contains approximately a 500-fold higher frequency of stem cells and tissue collection is simple,” Dr. Roelofs said. “Moreover,” Dr. Sara M. Melief added, “400,000 liposuctions a year are performed in the U.S. alone, where the aspirated adipose tissue is regarded as waste and could be collected without any additional burden or risk for the donor.” For the study, the team used stem cells collected from the bone marrow and fat tissue of age-matched donors. They compared the cells’ ability to regulate the immune system in vitro and found that the two performed similarly, although it took a smaller dose for the AT-SCs to achieve the same effect on the immune cells. When it came to secreting cytokines — the cell signaling molecules that regulate the immune system — the AT-SCs also outperformed the bone marrow-derived cells. “This all adds up to make AT-SC a good alternative to bone marrow stem cells for developing new therapies,” Dr. Roelofs concluded. “Cells from bone marrow and from fat were equivalent in terms of their potential to differentiate into multiple cell types,” said Anthony Atala, M.D., editor of STEM CELLS Translational Medicine and director of Wake Forest Institute for Regenerative Medicine. “The fact that the cells from fat tissue seem to be more potent at suppressing the immune system suggest their promise in clinical therapies.” Read full peer reviewed article
Most people would be happy to get rid of excess body fat. Even better: Trade the spare tire for something useful — say, better-functioning knees or hips, or a fix for an ailing heart or a broken bone.
The idea is not far-fetched, some scientists say. Researchers worldwide are repurposing discarded fat to repair body parts damaged by injury, disease or age. Recent studies in lab animals and humans show that the much-maligned material can be a source of cells useful for treating a wide range of ills.
At the University of Pittsburgh, bioengineer Rocky Tuan and colleagues extract buckets full of yellow fat from volunteers’ bellies and thighs and turn the liposuctioned material into tissue that resembles shock-absorbing cartilage. If the cartilage works as well in people as it has in animals, Tuan’s approach might someday offer a kind of self-repair for osteoarthritis, the painful degeneration of cartilage in the joints. He’s also using fat cells to grow replacement parts for the tendons and ligaments that support the joints.
Foremost among fat’s virtues is its richness of stem cells, which have the ability to divide and grow into a wide variety of tissue types. Fat stem cells — also known as adipose-derived stem cells — can be coerced to grow into bone, cartilage, muscle tissue or, of course, more fat.
Cells from fat are being tested to mend tissues found in damaged joints, hearts and muscle, and to regrow bone and heal wounds.
The stem cells in fat share the medical-worthy spotlight with a few other cells. Along with the fat-filled adipocytes that store energy, fat tissue has its own blood supply and supporting connective tissue, called stroma. The stroma contains blood cells, immune cells, endothelial cells that line the inner surface of blood vessels and pericytes, which line the outer surface. These other fat-derived cells are proving to have therapeutic value as well.
Plastic surgeon J. Peter Rubin, also at Pitt, says that the multitalented cells found in fat could prove to be the ultimate body repair kit, providing replacement tissue or inspiring repair of body parts that can’t mend themselves.
Much of the research — more than a decade of studies — has been in lab animals, but a few applications are being tested in human volunteers. Current clinical studies under way aim to provide replacement tissue to treat chronic wounds and diabetic sores, or conditions such as Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease and type 1 diabetes.
Most clinical studies use the simplest approach: Harvest cells from a patient, then inject them in a single procedure. In more complex approaches still in lab and animal testing, various cells in fat are extracted and manipulated to create custom treatments for worn-out or damaged tissues or to generate blood flow after a heart attack or replace bone in large fractures.
Questions remain, however, about how the cells do their regenerative magic. Scientists and regulators still have plenty to figure out, such as what cell characteristics work best for each application.
A lush source
Stem cells can develop into various cell types, which makes them the focus of studies that aim to replace cells that fail because of disease, accident or age. Stem cells taken from embryos are more versatile than other types of stem cells, but their use is controversial. For that reason, researchers have studied stem cells from sources other than embryos, including bone marrow, muscle and blood.
Fat tissue comes from the same embryonic tissue as bone marrow, a traditional stem cell source, so scientists reasoned that fat might contain similar cells. In 2002, UCLA researchers discovered stem cells in human fat. They were surprised to find vast quantities.
Stem cells make up 2 to 10 percent of fat tissue. A cubic centimeter of liposuctioned fat (about one-fifth of a teaspoon) yields 100 times as many stem cells as does the same amount of bone marrow, Tuan says. And fat cells are easy to harvest — much easier than bone marrow. One pound of fat removed from a patient’s abdomen can yield up to 200 million stem cells, a more than adequate supply for treatments.
Why fat produces so many stem cells isn’t clear, but Rubin points out that fat tissue serves several important functions. In addition to storing and releasing energy, it helps insulate and protect the body’s internal organs. “Like most tissues in the body, fat has a reservoir of stem cells to replenish cells as they die off or create new cells in response to growth or the need for more cells,” he says.
Fat produces so many stem cells, in fact, that for some applications — such as tissue-replacement or “fat grafting” — there’s no need to grow more of them in the lab. Once harvested, liposuctioned material is treated with enzymes to remove cells from the surrounding tissue, then put into a centrifuge to separate the stem cells from other cell types. In about an hour, the stem cells are ready to be injected back into the patient to plump skin or round out fat tissue lost to injury or disease. Rubin has used this method to treat patients who have lost tissue during breast cancer surgery or have been injured in war. His lab is conducting a clinical trial on the use of fat stem cells to plump up tissue at the site of an amputation to improve the comfort and fit of a prosthetic arm or leg or to make it easier to tolerate sitting for long periods in a wheelchair.
Already, Rubin’s team has treated five military patients, extracting fat from each patient’s abdomen and injecting the stem cells back into the patient at the injury site. He and other scientists think that the fat stem cells remodel tissue by releasing growth factors and communicating with surrounding cells in their new location — sending and receiving signals through chemical cues. As a result, the stem cells enhance the growth of new fat tissue and boost blood supply to surrounding tissue. Over a period of several weeks, the cells he injects form a mound of fat tissue, allowing patients to fit a prosthesis or sit without pain. So far, all of the patients have benefited from the stem cell injections, he says, though his group is still working on how much to inject for each patient. Read full peer reviewed article