Stem Cells: Autologous or Allogeneic Transplantation? That Is the Question.

For more info on stem cells go to earlier blog post http://drbradstreet.org/

Part 3. Stem Cells: Autologous or Allogeneic Transplantation? That Is the Question.
March 6, 2011
drbradstreet

Practically speaking we have two potential choices for stem transplantation. Self-donated (autologous) means a small amount of bone marrow or fat (adipose) is removed, stem cells are isolated and then returned to the same patient. Allogeneic means another human donor provides the stem cells. For all intents, what happens to the stem cells after harvest could be identical except for the who is giving part.

Just to further clarify the transplantation issue, there is something called: Xenotransplantation (xenos- from the Greek meaning “foreign”) which is the transplantation of living cells, tissues or organs from one species to another, such as from pigs to humans (borrowed from wikipedia- thanks wiki). The best example of this would be using pig heart valves for humans.

I am absolutely opposed to the routine use of xenotransplantation (with a few exceptions like heart valves) and that certainly applies to stem cells. I think we are asking for trouble when we start mixing species. Forgive me for remembering my high school Latin: Sui generis (each to its own kind). Yes, I know there are doctors on the web or even running around Southern California advocating the use of rabbit or even rat stem cells. For Real?

Yes! But it’s not for me and certainly not for my patients. And it’s not for the FDA either (section 351 of FDA code).

So back to our question: in nearly all cases autologous (self-donated) is ideal. As an example, when my anterior cruciate ligament was torn and couldn’t be repaired, I needed a graft. I was offered a banked donor tendon, or the use of part of my own patellar ligament. Using my own would include carving out the middle portion of the ligament that attached my kneecap to my lower leg bone. It would involve a lot more downtime and be significantly more painful. But is was mine and it was living and more likely to revitalize than a donor’s devitalized ligament. The choice was painfully obvious; I used my own patellar ligament and the outcome has been better than I expected (although I don’t like to think about the first 2 years after surgery).

I realize my knee analogy doesn’t perfectly fit what we are doing with stem cells, but it is fair enough – especially given the regulatory restrictions on stem cells. My overall take is the use of self-donated stem cells are the easiest/best to use for many reasons. I fully realize they may lack some of the zip intrinsic in embryonal or fetal stem cells. Regardless of the religious/moral issues, these are currently illegal in the US and they cause too much controversy for most doctors to work with clinically.

There are, however, cases where the individual’s health may be so compromised, or the challenges of getting stem cells from them are so difficult, that we may need to consider a donor. Let’s look at this allogeneic issue before finishing up on autologous stem cells.

As a bit of a background, medicine has a long history of using donor tissues and organs. If you think about it – a simple blood transfusion is a donor (allogeneic) transfer. The first successful human to human transfusion took place in 1667, long before we even understood blood type. Remarkably, the first human donor transplants seem to have taken place in the 3rd century, but little is recorded about the successes or failures.

Despite serious problems from transplant rejection, the process took place largely unsuccessfully until the advent of immunosuppressive medications to prevent the rejection. Today, if someone needs a kidney from a donor to live, nearly every one is comfortable with idea. We use donors for corneas, kidneys, hearts, bone marrows, and livers (to list some of the most popular). These types of allogeneic transfers have been accepted and sought after by the people who needed them.

I am a registered bone marrow organ donor and routinely donate blood, so you know I am a believer in the use of allogeneic tissue donations. The safety rules around donation of organs and blood apply equally to donation of stem cells. Any donor – even a family member – would need infectious disease screening. And just like volunteer donors for any organ or even blood, we first have to make sure the donor can withstand the donation. That seems more than obvious when you are talking about giving up a kidney you are still using, but who cares about giving up some fat. I agree (assuming all the other safety issues are considered). There is however one rather sticky situation: the use of minors – like siblings – as donors.

Here the ethics get complicated. Can a parent volunteer their under-aged child to donate to another child? Regardless of the legal considerations my first instinct is to say no. However, there may be compelling reasons to consider it in special situations for something as minor as adipose donation.

The actual process of lipoaspiration (not the more invasive liposuction you may be thinking of) is of very little risk and minimally painful. The risks of infection are extremely small and the risk of reacting to the small amount of lidocaine used in the process is even smaller. Post-operative bleeding/bruising is also trivial in nearly all cases. The amount of fat donated is small for adults, but even less for children.

Children’s adipose provides about one stem cell per 500 -1000 fat cells. As the slide below illustrates, bone marrow has far fewer stem cells and for all practical purposes to be used it must first be cultured to amplify the number of stem cells. That process makes it off-limits in the US.

LOSS OF BONE MARROW STEM CELLS WITH AGE - see image below

As you can see – adipose is a much denser source of stem cells, such that a child may only need to donate 20 ml (4 teaspoons) of fat in order to generate significant stem cells. That would also be true if a child was self-donating. For cosmetic reasons, fat donation always needs to be taken symmetrically from both sides of the body. For a midline donation, like around the belly-button, that can be accomplished with one tiny 3 mm incision. If we are harvesting stem cells from other areas, like the posterior armpit area, we will need two incisions. None of this technically complex on the surgery side, nor does it require an operating room. These types of procedures are being done routinely in the outpatient setting.

Further complicating our choices of sibling or child donation; the stem cells of children possess superior reproductive qualities making them technically better than older stem cells. Despite all of these factors, before any parent can allow a sibling – sibling and especially a child to parent donation, it will require approve of an ethics committee. I don’t think it is wise for the parents and treating doctors alone to make that decision.

The bottom line: For now, the simplest approach is autologous (self) donation of adipose (fat) for stem cell harvest and implantation.