Adipose-Derived Stem Cells: A Review

Imagine a veterinarian harvesting stem cells from a horse: He or she inserts a needle into the horse’s sternum or hip, and thick red bone marrow fills the syringe. But can you picture a veterinarian harvesting less commonly-used adipose-, or fat-, derived stem cells? And how effective are they? Joseph Yocum, DVM, Dipl. AVBP, owner of Green Tree Veterinary Service and the Centre for Regenerative Medicine in Danville, Ky., presented a review of adipose-derived stem cells at the 2011 North American Veterinary Regenerative Medicine Conference held June 2-4 in Lexington, Ky.

Yocum explained that research indicates adipose tissue is a reliable source from which to collect stem cell aspirates.

“Adipose tissue is easy to harvest, yields a large number of cells, and, thus, does not require tissue expansion and has the potential to differentiate into a number of specialized cells of mesodermal origin,” Yocum explained.

Adipose-derived cells can be harvested from a few different areas on the horse’s body; however, the most common place from which to harvest is the hindquarters–particularly from the fat located near the horse’s tailhead. Yocum noted that, “Fat can be harvested from the inguinal (groin) area, and there is some discussion of harvesting from the neck, but I don’t know of anyone that has tried that yet. The tailhead area is the easiest since the inguinal area requires general anesthesia.”

Yocum explained that there are two ways to harvest adipose-derived stem cells: a surgical linear incision and liposuction. He noted that the linear incision is the most straightforward; however, liposuction is more cosmetic. Both approaches yield about the same amount of nucleated cells per gram and the same cell viability, he added, indicating there’s little difference between the two methods’ efficacy.

“Recent advances, including improved enzymatic digestion that allows us to increase cell yield, in the processing of adipose tissue have substantially improved the cell concentration and total cell counts from harvested fat,” Yocum added. “This precludes the need for cell expansion (the process by which stem cells are proliferated until enough are available for a treatment, which can take days or weeks to complete with other types of stem cells). In most cases, cells are available for same day injection.”

Yocum also noted that adipose-derived cells have shown:

• The ability to develop into osteocytes (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells), and tenocytes (tendon cells);
• The ability to transdifferentiate (when an already differentiated stem cell creates cells outside its established differentiation path) into cells of other germ origins (“This is new, but via transdifferentiation cells from other germ origin other than mesenchymal origin have been experimentally produced,” Yocum noted.); and
• That they have large numbers of growth factors, proteins, pericytes (a connective tissue cell that occurs about small blood vessels), blood cells, and fibroblasts (cells that form connective tissues). Yocum explained that, “Growth factors are essential to stimulate stem cells to differentiate into the target cell.”

Finally, Yocum explained that when platelet-rich plasma therapy is used in conjunction with adipose-derived stem cells, the stem cells are further stimulated to proliferate and differentiate. Also, evidence suggests that photostimulation (the process whereby certain wavelengths of light stimulate cell proliferation) activates the adipose-derived stem cells. However, he noted that the reason behind this remains to be discovered.

Yocum noted that while some parties favor using bone marrow-derived cells and others favor adipose-derived stem cells, current research indicates that both stem cells are likely equally effective in helping injuries heal.

Often, he added, a veterinarian bases his or her decision to use bone marrow- or adipose-derived stem cells on several factors: “The decision is based on a number of factors including ease of harvest, cell numbers, and the interval between harvest and injection (adipose-derived cells can be ready within hours whereas bone marrow-derived cells must be expanded, which can take weeks).”

Cost is another consideration: “I am not sure about the cost of collecting and expanding bone marrow-derived stem cells, but I feel that adipose-derived stem cells are reasonably priced,” said Yocum, who charges $1,495 at his practice for adipose collection, processing, and the first treatment. “Also, since we get such large numbers of cells we have the option of freezing a portion of the collection, which allows multiple treatments from a single collection.”

Regardless of whether the treating veterinarian chooses bone marrow- or adipose-derived stem cells, Yocum said that the future of regenerative medicine is bright, but more research is needed to determine the best applications.

“I am excited about the potential of regenerative medicine,” he concluded. “We have developed novel treatments using stem cell for musculoskeletal injuries–injuries that before had no effective treatment–and we’re getting excellent results.

“In addition to this area of medicine I believe we will discover new applications for a number of other medical conditions as well,” he continued. “It is important to me that we approach this with a practical mindset as we develop treatment protocols for these other conditions, muscle disease, liver disease, pulmonary disease, neurologic disease, as examples. All the time moving forward and learning what works and what does not work.”

Courtesy of Joseph Hall

Stem Cells Help Irradiated Mice Grow New Brain Cells

Radiation treatment for brain cancer can be lifesaving, but it can come at a terrible cost. The radiation that kills cancer cells also kills brain cells, destroying memories, impairing intelligence, and causing confusion.

Charles Limoli and colleagues at the University of California, Irvine, have shown that stem cells could help reverse some of this damage. In a new paper in the journal Cancer Research, Limoli shows that it’s possible to cause new brain cells to grow by injecting human neural stem cells into the brains of mice whose cognitive abilities had been damaged by radiation. The mice regained lost skills after the stem-cell treatment.

Stem cells have long been used to repair the damage caused by cancer treatment. Bone-marrow transplants for leukemia rely on stem cells to replenish blood cells, for instance. But Limoli says his team is the only one using neural stem cells to treat symptoms in the brain.

Several peers praised his work, calling it an important proof of the idea that human stem cells can repair neuronal damage.

“The results are very promising,” says Howard B. Lieberman, professor of radiation oncology and environmental health sciences at Columbia University. “If the findings continue to be as positive as what’s published in this paper, I would assume Dr. Limoli will take great effort to try to move it into the clinic as quickly as possible.”

Limoli’s team irradiated three groups of mice, later treating two of them with human neural stem cells. The third, a control group, received a sham surgery, but no cells were implanted. One month after the damage, 23 percent of implanted stem cells were active in the brains of the first group of mice. After four months, 12 percent were still active in the second group. Using cellular labeling, Limoli’s team also showed that tens of thousands of new neurons and astrocyte cells had grown in the brains of the treated mice. The treated mice performed better than the untreated ones on cognitive tests, and recovered their preradiation abilities.

Protein activity in the treated mice suggests that the implanted stem cells are integrating into the brain, Limoli says, replacing cells that have been lost or damaged.

Both Limoli and Lieberman say the treatment could also be effective against “chemo brain,” a side effect often reported by breast cancer patients who say their ability to focus and think clearly has been impaired by chemotherapy.

Rob Coppes, a radiation and stem-cell biologist at the University Medical Center Groningen, in the Netherlands, says he would next like to see Limoli test how long the benefits of the stem cells last. He also hopes Limoli will repeat his experiments using induced pluripotent stem cells (iPS cells), adult stem cells that have been converted back to an embryonic-like state. These would likely be the cells that doctors would use in patients. Ideally they’d be taken from the patients themselves to avoid an immune rejection.

It will be important to show that mice—and later, humans in a trial—don’t reject these cells, and also that the stem cells don’t trigger new cancers, says Coppes, who employs stem cells in his own work, which involves regenerating salivary glands.

Limoli plans to carry out further work involving human neuronal stem cells and iPS cells. He also wants to figure out the optimal time to transplant these stem cells into the brain

VetCell has partnered with RenovoCyte LLC’s equine stem cell treatment Autocell-EQ

RenovoCyte, LLC announced today a strategic partnership with Equine Partners of America (EPA) doing business as VetCell Americas. VetCell enjoys a well-established equine stem cell business in the United Kingdom and is now moving into the United States with the help of EPA in Atlanta, GA. RenovoCyte, LLC will be responsible for the processing of VetCell’s mesenchymal stem cells from equine bone marrow and in-house veterinary support for VetCell’s equine treatments in the USA.VetCell is a leading veterinary medical technology company offering personalized service to veterinarians for the treatment of equine leg injuries and lameness.

Renovocyte will process and/or store pure stromal stem cells from bone marrow for VetCell’s stem cell therapy for horses with injured tendons and ligaments then send the cellular treatments to the veterinarians for injection into the patients injured site.

VetCell Americas also acquired an agreement from RenovoCyte, LLC to carry RenovoCyte’s equine intravenous stem cell product, Autocell-EQ. RenovoCyte’s innovative stem cell technology allows intravenous treatments of exercise induced pulmonary hemorrhage (bleeders), rhabdomyolysis (tying up) and
osteoarthritis in the horse. RenovoCyte Cellular Medicine Laboratories in the U.S. isolates multipotent stem cells from innovative sources such as the wolf teeth, skin biopsies, placenta and testes then cryopreserves the sample using their Wellness BankingTM protocol or cultures the cells to a known dose for autologous intravenous therapy.

Targeted Diseases for RenovoCyte’s equine stem cell therapy include:
– Osteoarthritis
– Exercise Induced Pulmonary Hemorrhage (Bleeders)