Stem Cells Cure Man's HIV

If you haven't seen this story, it's an amazing triumph for adult stem cell therapy and HIV. However, one man's gain is another man's loss.  What should be read between the lines is that the genes of the donor stem cells (the ones that were able to take out HIV by crippling the CCR5 receptor) still functioned in the host.  Why is this important?  It means that stem cells transplanted from person A to B can carry with them genes and their gene functions.  This comes on the heels of another study which showed that mice bred to have osteoporosis were able to transmit that disease to normal mice without known bone problems.

Who cares?  Well, companies pursuing allogeneic stem cell products should be very concerned by this finding.  It means that off the shelf stem cells likely carry with them all of the good and bad genes from the donor into the host.  This means that until we know everything there is know about the upside and downside of every gene, inserting new genes into people is a huge risk.  It means allogeneic stem cells plays (embryonic, cord blood, and adult donor cells) are really gene therapy plays.  While this may prove revolutionary for curing the most deadly diseases (like HIV or GVHD), where the benefits outweigh the unknown risks, for everyday diseases, the potential risks likely outweigh the benefits.    

Another Blow to Fat Cells for Ortho

Despite a rash of media coverage of the use of a dilute fat stem cell concentrate (nucleated cell centrifuge spin) in dogs, another study was published this week showing that adipose derived stem cells continue to dramatically under perform bone marrow and synovial derived stem cells in chondrogenesis (cartilage production). For a more complete literature review at the National Library of Medicine, click here. While fat derived MSC's appear to be very good at immune suppression, cosmetics, and perhaps nerve repair, for ortho they under perform on bone, tendon, ligament, and cartilage applications. While this is a very attractive business model (have patients undergo liposuction and fix their joints), the research just doesn't stack up. So while the business is Phat, the research is flat.

Injecting Adult Stem Cells IV Doesn't Work (Unless You Have a Lung Problem)

A recent study has shown what seemed obvious, out of country stem cell outfits injecting adult stem cells IV fail to get those cells to the target organs being treated.  These cells don't end up in the brain, liver, heart, joints, etc... they end up in the lungs.  This is similar to the first pass effect seen in drug delivery (in that case it's the liver).  Credible stem cell delivery is direct to the target organ or tissue.  So if you want cells in the pancreas, you have to place them there.  If you want cells in the joint, again you have to place them in the joint.  Organizations doing this type of credible adult stem cell delivery include Regenerative Sciences  and Regenocyte.  

Stem Cell Mania

There is an underground explosion in cell based medicine brewing.  There already lots of players.  I would break them into the following categories:

1.  Magic:  Lots of these in Europe and Central America as well as third world countries.  The source and type of the cells being used is unclear.  Rather than placing cells in the areas that need treatment, they prefer the more profitable route of injecting them IV.  These companies will treat anything from diabetes to spinal cord injury to ALS.  This is truly the "wild west" of stem cells.

2.  Storage:  Lots of these abound.  Cord blood, peripheral blood CD34+ cells, other blood based progenitors.  While some of these have some science, they all suffer from a lack of the ability to deploy cells to treat disease, so convincing patients to donate cells can be tough.  The most successful of these appears to be cord blood storage.  The best of these companies are those like Neostem, who have scientific focus and high level medical direction.

3.  Big pharma: This is for the most part an off the shelf stem cell solution.  The idea is creating the world's next Penicillin.  The practical problem is even if this works, it will be many years before the details of treatment protocols are worked out.

4.  Stem Cell Application Providers:  This would include the Regenexx procedure.  It would also include companies like Regenocyte.  These groups take more of a scientific approach, use a verifiable cell line, and place the cells at the site in need of repair.  They have expereince with actual working treatment protocols for specific diseases.

5.  Stem Cells in a Box:  These are bedside centrifuge or processing plays.  These boxes produce a very dilute stem cell population (like the Harvest system).  While they quote big numbers of cells, their literature is grossly misleading.  The cell numbers quoted are for CD34+ blood stem cells which aren't usually considered true multi-potent adult stem cells.  So while this cell population might help tissue repair in a young person, in a middle aged person and beyond, the stem cell numbers that count are too dilute to matter.  

Big Pharma Should be Very Concerned...WBC's from the Patient Could Cure Serious Disease

Recent research on autologous WBC's has been nothing less than miraculous Two new articles are important.

The first potential break through is in cancer research. A researcher at Wake Forest is convinced that cancer is caused by white blood cell suppression. In other words, our WBC's fail to do their job of picking off the cancer cells that brew in our bodies every day. However, this researcher believes that by taking healthy WBC's from donors he can cure cancer (at least in mice). This has so upset the traditional oncologic research community that he has been unable to get grants for his work. As a result, he is asking patients to self-fund the first human trial.

The major development other involves rheumatoid arthritis. In this treatment, researchers from the U.K. take white blood cells, reprogram them using a chemical cocktail, then inject them into joints with rheumatoid arthritis. This has been effective in animals in curing the disease and early human trials are beginning now.

What's the upshot? If you can take someones cells and miniammly modify them or provide healthy cells from a donor and cure these horrible diseases, the big pharma business plan will be in disarray. Basically, these are blood banking or minimal culture treatments that combined, would eliminate hundreds of billions in cancer and RA treatment.

All this brings us back to an age of autologous biologics where the idea of using drugs and pharmaceutical cocktails to achieve results may be changed forever, or at least the playing field altered. Already we are seeing biologic approaches such as platelet rich plasma that are gaining popularity among interventional pain physicians and those who treat acute and sub acute sports injuries. In addition, autologous stem cell approaches are allowing the treatment of chronic joint diseases. All of this points in a direction where the future will have a myriad of hybrid treatment approaches. In the end, we may all be using bits and pieces of ourselves as therapy.

A recent investigation into how mechanical loading can turn MSC's toward bone even if they are given chemical signals to become fat, has broad implications for exercise programs. While we fret about calories or eating too much fat, their study suggests that MSC's can become fat cells simply by lack of physical activity. Clinically, we likely see this in many AVN patients who may have part of their disease pathogenesis in their low activity lifestyle. I've always thought that in many of these patients their MSC's would prefer to become fat over bone (hence the lesion-where weak fatty marrow tissue replaces strong bone). This would also have big implications for a host of disease states that are likely activity related and involve poor bone formation such as osteoporosis. We've all known for sometime that being more active is good for our health and our bones, but this new research helps us understand that at the earliest stages of adult stem cell development, activity gives our cells clues to either strengthen our bodies or make them weaker. For example, most animal studies of orthopedic healing would suggest that even in bone or cartilage injuries, more activity promotes better repair. While this can be a two edged sword (too much activity on an injured part can cause it to fail while not enough will reduce the strength of the repair), many cell based treatments now recognize that promoting activity as quickly after the procedure is key to a good recovery. In other words, keeping an animal off a cartilage lesion "to let it heal", in general promotes new cartilage that is not as strong or chemically complete as when an animal is allowed to do what it wants (meaning some limping while it hurts and then full activity when it feels able).

The take home message? We Americans have gotten used to low activity levels that not only promote obesity by reducing our caloric burn, but also increase the tendency of our stem cells to turn into fat when they should be bone (and likely muscle, cartilage, tendon, ligament, etc... )

Et tu Cipro

Looks like another one bites the dust. The antibiotic drug class known by doctors as "The Quinalones" has just been awarded a "black box" warning from the FDA. Seems like these drugs can cause tendon ruptures and in one study tripled the risk of Achilles tendon rupture. Since these are first line antibiotics for various types of infections (including bladder and bone infections), this will have wide reaching impacts.

This general theme is also consistent with our research showing this drug class inhibits the growth of mesenchymal stem cells. In fact, our own research is suggesting a rather dismal picture for prescription drugs in general, many of which seem to inhibit adult stem cell growth. While it's been known for years that all of these drugs can have direct toxicity effects on the liver or kidney, or both organs, what has not been generally known is how they might impact the other side of the equation, namely how they might hamper the local repair effort. Until recently, modern medicine didn't understand that almost any tissue in the body is a balance between killing off cells in daily wear and tear and replacing those cells with local stem cells. While many drugs negatively impact cells of various types (organ cells or in this case cells that maintain tendons), what's also likely happening is a negative impact on the cells who replace these dead or stressed organ cells (adult stem cells). If this data holds up (we have been collecting this for the past few years), it will have wide reaching effects on modern allopathic medicine, namely many prescription drugs are not only directly hurting certain cells, but also killing off the repairmen who are supposed to fix that damage.