Five Stem Cell Companies in Orthopedics

Five companies, we think, stand out when it comes to non-allograft stem cells. In reverse rank order, here is who we think are likely to make the biggest stem cell splash in orthopedics.

RNL BIO Co., Ltd. — Presidential candidate (and Governer of Texas) Rick Perry received stem cells for back pain using RNL BIO’s system earlier this year. Stanley Jones, M.D., associate clinical professor at the University of Texas Medical School at Houston was Perry’s doctor. What makes this story so compelling is that Dr. Jones had first tried the therapy on himself.

In September 2009, Dr. Jones was operating on a very long case when “My right wrist started to swell and I’d never had such severe pain in my life. I really had no idea what was wrong.” So Dr. Jones asked his wife, who is a nurse, to inject his wrist with cortisone. “Two days later the pain was gone so I thought ‘the cortisone did it! This is great.’”

But the pain soon returned. “My knee started to swell. I had never had so much pain. Wow, I thought, I had it in my wrist now I have it in my knee.” Dr. Jones immediately went to his rheumatologist and was told that he had autoimmune arthritis.

Recalls Dr. Jones: “He (the rheumatologist) was quite frankly amazed at how much pain I was having. My physician assistant had to carry me into the office the pain was so bad. So I was pretty distressed. I just imagined that my practice in medicine was gone.”

Dr. Jones contacted RNL BIO and signed up for its stem cell therapy program. “We went to our medical spa and we had fat taken from our abdomen, our own fat. Our own fat cells were then sent to Korea and they were put in tissue culture. Two months later, glory be, we were in Japan getting stem cells. I was overwhelmed by how easy it was, by the cleanliness and the professionalism of the hospital in Kyoto. By the middle of October, I no symptoms at all and I’ve not taken anything since September. Thank God I got well.”

Link to video of Dr. Jones is here.

Korean based RNL BIO’s system, as Dr. Jones described, harvests adipose tissue, isolates the stem cells, cultures them into larger quantities and then, because treating patients with stem cells is not approved in South Korea, injects those cells into patients at affiliated clinics outside Korea. In the U.S. RNL BIO has opened clinics in Los Angeles and San Diego. Tissues extracted from patients in the U.S. are sent to labs in Maryland or Korea for expansion. The cultured cells are then injected back into the patients in RNL BIO’s partner facilities in China, Japan or Mexico.

Courtesy of Governor Rick Perry, RNL BIO’s stem cell system for treating back pain or, indeed, any orthopedic procedure has been thrust into a presidential campaign spotlight.

SpineSmith (aka Celling Technologies) — Every month Celling Technology’s (based in Austin, Texas) systems are used to treat about 350 orthopedic patients with stem cells. Roughly 200 patients are in Texas.

The company introduced its line of point-of-care, advanced bone-marrow-derived stem cell concentration systems in 2006. Today the company markets the ART 21, the Fusionary system and the MarrowXpress system.

Celling’s technologies work at the point-of-care. It’s an automated, closed system that concentrates bone marrow to a user-defined volume in about 30 minutes. The system retains more than 90% of the patient’s mononucleated cells. It’s self-powered and microprocessor-controlled. So it’s very precise.

Celling also provides a service delivery team staffed with trained registered nurses to operate the systems. Most of Celling’s sales are to surgeons performing lumbar or cervical fusions. Coming on strong are soft tissue knee and shoulder repairs and trauma.

Dr. Lee at University of California - Davis and Dr. Rodeo at Hospital for Sspecial Surgery (HSS) are studying the use of Celling’s systems for long bone non-unions and a rotator cuff repair.

Bottom line: Celling Technologies is putting the ability to harvest autologous stem cells into the orthopedic surgeons’ hands.

Aastrom Biosciences, Inc. — The first clue something was up was when Aastrom’s CEO bought stock. On August 5, 2011, Tim Mayleben, CEO, filed a notice with regulators to buy 20, 000 shares for around $2.36 per share. Then, three days later, he bought 10, 000 more shares at $2.11 per share.

Two days after that (August 10) Aastrom’s CFO, Scott Durbin, bellied up and bought 10, 850 shares for $2.18 - $2.24 per share. Not to be left out, Aastrom director Ronald Cresswell filed his papers and purchased 20, 000 shares at $2.22 per share.

All this buying happened in the middle of one of the broadest stock market sell offs ever. It reminded us of the Dan Akroyd and Eddie Murphy scene in “Trading Places” where the two men stand in an emotional selling frenzy buying everything they can.

What did Mayleben, Durbin and Cresswell know? Could they know something all of those big, smart institutional sellers didn’t?

On August 15, Aastrom held a conference call with Wall Street analysts and announced the FDA had reached an SPA agreement with the company regarding its Phase 3 Critical Limb Ischemia (CLI) trial. The trial is testing Aastrom’s expanded multi-cellular therapy for no-option CLI patients. Under the agreement, Aastrom could start the final phase of its CLI trial in 4Q11.

Ah yes, THAT CLI trial. It had been about a year since Aastrom announced Phase II results. Those results (multi-center, randomized, double-blind, placebo-controlled trial) showed that Aastrom’s autologous cells prevented amputations better than a placebo (P<0.05). Aastrom's trial is the largest blinded, randomized cell therapy study currently being conducted for CLI.

People with CLI face a high risk of leg amputation and in some cases death. Approximately 1 million patients in the U.S. suffer from CLI. The disease results in more than 160, 000 amputations each year.

One Wall Street broker, Needham & Company, immediately reiterated its long time “Buy” rating and a $6.00 price target. The stock? The day after Aastrom’s’ announcement it fell by a penny to $2.61 a share. The astute masters of Wall Street rendered their judgment. They yawned.

We noticed.

Osiris Therapeutics, Inc. — The U.S. Government is about to be the largest purchaser of stem cell products in the world. Three years ago the Department of Defense gave a $224.7 million contract to Osiris for its adult mesenchymal stem cell (MSC) therapy as a medical countermeasure to nuclear terrorism and other radiological emergencies. Upon FDA approval of Osiris’s product (in Phase 3 Animal Rule trials), the U.S. Government will purchase at least 20, 000 doses at $10, 000 per dose. And then stockpile these doses in freezers around the United States.

(The FDA Animal Rule states that the FDA may grant marketing approval based on adequate and well-controlled animal studies when the results of those studies establish that the drug or biological product is reasonably likely to produce clinical benefit in humans.)

The reason this matters to orthopedics is because the underlying etiology of radiation sickness is almost identical to the underlying etiology of arthritis and other autoimmune diseases.

MSCs are stimulated by biochemical stimuli and move through the blood stream to points of inflammation (like arthritis). Once there, MSCs coordinate healing and tissue regeneration at that point of injury or inflammation by producing growth factors, blocking inflammation and reducing scarring. Importantly, MSCs do not trigger the patient’s immune system.

Soon the U.S. Government will begin to stockpile injectable doses of stem cells around the U.S. Why? Because the government is convinced that mesenchymal stem cells treat the kind of systemic inflammatory responses that occur due to radiation exposure—but also occur due to arthritis—and do so safely.

Mesoblast Limited — No stem cell company has launched more clinical programs aimed at the orthopedic surgeon than Australia’s Mesoblast. Over the course of the last three years Mesoblast has:

1. Received FDA’s clearance to begin Phase 2 clinical trials of its stem cell product NeoFuse for fusion of the cervical spine in the neck. The study compares two doses of NeoFuse against standard-of-care in 36 patients requiring bony fusion at 2 or more levels in the cervical spine. Mesoblast’s preclinical trial results for NeoFuse showed earlier and more robust bony fusion of the cervical spine over a three-month period than either a recipient’s own bone (autograft) or synthetic material, with no cell-related adverse events.

2. Completed a pilot clinical trial for non-healing, long bone fractures in the legs. Using Mesoblast’s stem cell product, physicians were able to achieve bony union and healing within a median time of approximately four months versus what otherwise would have been permanent non-healing of the fractures in the absence of cell therapy.

3. Reported exceptional results of a preclinical cartilage trial which showed that a single injection of Mesoblast’s allogeneic cell product, RepliCart, into knee joints damaged by osteoarthritis can prevent further deterioration and regenerate and regrow cartilage tissue lining the damaged joint.

4. And finally, as reported at the New York Stem Cell Summit two years ago, showed in a preclinical trial that a single, low dose of Mesoblast’s allogeneic adult stem cells into severely damaged intervertebral discs could dramatically reverse the degenerative process, regrow disc cartilage and normalize the disc anatomy and function.

All of this was, in effect, captured when pharmaceutical firm Cephalon agreed to pay Mesoblast $130 million upfront and another $220 million to acquire a nearly 20% stake in the company. With regulatory milestone payments Mesoblast could receive up to $1.7 billion from Cephalon.

These firms either have stem cell products on the market or are in the advanced stages of bringing therapeutic stem cells to rank and file orthopedic surgeons.

So, now that you’ve read our picks, let us know what you think.