AdultStemCell.com

It is widely accepted that stem cells are involved in tissue regeneration. It is also widely accepted that (in most organs) stem cells are vanishingly rare. So: if there doesn’t happen to be a stem cell adjacent to a site of damage, how can stem cells be involved in the process of tissue repair?

One possible answer: There might be more stem cells than we think, because we’ve been missing them for some reason. This possibility (”both”) is strongly supported by the recent findings of Zuba-Surma et al., who have discovered a population of tiny pluripotent cells (termed, appropriately, very small embryonic-like, or VSELs) scattered throughout the body.

Very small embryonic-like stem cells in adult tissues—Potential implications for aging

Recently our group identified in murine bone marrow (BM) and human cord blood (CB), a rare population of very small embryonic-like (VSEL) stem cells. We hypothesize that these cells are deposited during embryonic development in BM as a mobile pool of circulating pluripotent stem cells (PSC) that play a pivotal role in postnatal tissue turnover both of non-hematopoietic and hematopoietic tissues.(cont.)

During in vitro co-cultures with murine myoblastic C2C12 cells, VSELs form spheres that contain primitive stem cells. Cells isolated from these spheres may give rise to cells from all three germ layers when plated in tissue specific media. The number of murine VSELs and their ability to form spheres decreases with the age and is reduced in short-living murine strains. Thus, developmental deposition of VSELs in adult tissues may potentially play an underappreciated role in regulating the rejuvenation of senescent organs. We envision that the regenerative potential of these cells could be harnessed to decelerate aging processes.

Note that both VSEL number and potency diminish with age, consistent with the decrease in proliferative and regenerative capacity that we see in older animals. (And recall that diminishing stem cell potency is just one side of the story: over the course of aging, tissue microenvironments themselves grow more hostile to stem cell growth and function).

The small size of the VSELs, along with their dispersal throughout the body, might explain why they’d been missed up until now. It makes sense that cells devoted to long-term storage of regenerative potential would be very little: other than surviving and maintaining the ability to respond to proliferative signals, they wouldn’t really have much in the way of functional requirements, and wouldn’t need much more than a nucleus, a membrane, and extremely vigilant signal-transduction pathways — the latter ready to awaken the dormant cell when it’s time to turn into a proper stem cell, divide, and differentiate. In a sense, then, these VSELs are not so much progenitors as “progenitor progenitors”, the of regenerative capacity lying silent until they are needed.

(Extending this admitted over-interpretation — small size, after all, does not mean low metabolism, but I’m reasoning by analogy to spores and other very small totipotent cellular forms — another advantage of keeping stem cells metabolically inactive is that they would be less likely to suffer mutations or other damage that could convert them into cancer stem cells.)

Required skepticism: VSELs are both brand new and (so far as I can tell) idiosyncratic to a single group’s work. Before we get too worked up about this, I’d like to see the work reproduced by other labs and in other systems. Hopefully that sort of confirmation is already underway.

Chip is a frisky, friendly 3-year-old chocolate Labrador. He’s also a cutting-edge laboratory experiment.

While the promise of stem-cell therapies remain largely unfulfilled for humans, they are succeeding in leaps and bounds in dogs like Chip, whose transplant for his elbow dysplasia did what drugs, physio, water therapy and two surgeries could not. Elbow dysplasia, common in certain dog breeds, is a condition involving multiple developmental abnormalities of the elbow-joint.

“It’s so exciting that they can do this,” says Toronto resident Anne Molloy, about the April transplant of her pet’s own stem cells.

Chip started limping at age 3 months, although he still loved to play and fetch, Molloy says. “You’d throw the stick for him and he’d start running, then buckle,” she says. “We could never take him on a walk. It was very sad.”

By a year his limp was bad enough that strangers constantly approached with concern and advice and he required a high dose anti-inflammatory and pain medication. After trying everything else, Molloy decided to try using her animal’s own ability to heal itself.

The therapy, by San Diego’s Vet-Stem, a company specializing in regenerative veterinary medicine, has been used successfully on horses since 2004 and dogs for the last 18 months.

About 3,500 horses and 2,000 dogs have been treated for hip and elbow dysplasia, osteoarthritis and tendon and ligament injuries, with success rates between 75 per cent and 95 per cent, according to survey results from veterinarians and owners, says company founder Bob Harman.

Here’s how it works:

While the animal is under general anesthetic, several tablespoons of fat are extracted from the abdomen or behind the shoulder, which is shipped overnight to the San Diego lab. That’s the worst part for the dog. On receipt of the fat, clinicians separate the stem cells from all other tissue, count the cells and divide them into proper doses within four hours, shipping one or two doses back to be injected into the joint the following day. The injection takes moments and is done under mild sedation.

Then magic seems to happen. The introduction of the stem cells to the injured joint signals anti-inflammatory cells and new blood cells to form.

It’s expensive – about $3,500 – but cheaper than joint replacement, which costs up to $10,000.

Some 2,000 veterinarians are certified to perform the procedure in the U.S., but there are fewer than 20 in Canada. Its launch here was six months ago in Halifax.

“In our clinic, we’re doing them almost every day, weekly certainly,” says Dr. Christine Zink, a veterinarian and professor at Johns Hopkins University School of Medicine in Baltimore, and an expert on canine agility. Other treatments have low efficacy, particularly compared to this, she says.

Most animals show reduced lameness, pain and swelling and increased range of motion within two weeks of the transplant, though improvement continues for up to six months.

That’s what happened to Chip, who perked right up, Molloy said.

Dr. Rona Sherebrin, of the Secord Animal Clinic, is the only vet certified by Vet-Stem in the GTA and practises at the clinic Molloy already attended.

“The fantastic thing about it is that it’s using the dog’s own tissue,” Sherebrin says, eliminating transplant complications and the need for immunosuppressive drugs.

Most fat extractions provide enough stem cells for four doses. The remaining ones are stored, frozen, at Vet-Stem, for the future, Harman says.

And future injections are usually necessary. The transplant works for about a year in most dogs, which means one extraction is usually enough for older dogs.

Some dogs can go longer, depending on their activity level, Sherebrin says.

The procedure doesn’t eliminate problems. Chip still needs some pain medication, but just a fraction of the high dose he required before. He also limps a little after hard play.

“If you’ve got a joint that’s abnormal and you heal it, it’s still got an abnormal shape and it’s still going to end up having more tendency to arthritic changes,” Sherebrin says.

The procedure is not approved in North America for people, although it’s in clinical trials in the U.S., Europe, Japan and Australia, Harman notes.