September 24, 2020

The Niche

Knoepfler lab stem cell blog

Patients stem cell Q&A#1: can clinic injections cause GVHD?

People ask me questions about stem cells all the time so I decide to do a new blog series answering your questions.

Today’s post is  the first in this new stem cell Q&A series.

Colonic_graft-versus-host_disease GVHD
H&E stained section showing Graft Versus Host Disease (GVHD) in the gut. Dying intestinal cells are evident and can be a hallmark of GVHD. Image credit Mark Ong. Creative Commons License.

Past series have included my Elephant in the Lab series that provides some insights into the craziness that sometimes goes on in academic research with sometimes biting science humor. I’ve also gotten many great questions on my Reddit AMAs both about stem cells and CRISPR.

I’m focusing today on a question about a specific possible risk from getting stem cell injections at for-profit, unproven clinics.

Can stem cells injected by clinics cause graft versus host disease (GVHD)?

It’s an interesting question and not one that I have heard that often until the last couple years. Recently patients have brought it up more often.

GVHD is more typically a risk from allogeneic (donor-derived) bone marrow or hematopoietic stem cell transplantation, mostly in cancer patients who have received chemotherapy but also potentially for patients with other blood disorders who get transplants.

Injected immune cells from another person can potentially lead to a damaging or even fatal immune response of the transplant back against the recipient. In other words, the graft (the injected cells) attacks the host. You can see an example of dying gut cells (apparently in a human patient, but I’m not positive based on the image description) with GVHD in the image of a section of intestine stained with H&E above.From teaching histology what we’d expect to see in a healthy gut crypt or gland is a solid ring of cells around each lumen in the middle, but in this image we see some cells in the darker-staining outer rings are dying and disintegrating because of being attacked by immune cells.

This attack is possible because the graft in this case is either stem cells that can become immune cells or immune cells that are present in, for example, a bone marrow transplant. Especially in the absence of a perfect or near-perfect match between donor and recipient, the donor cells may view their new home (the recipient’s body) as foreign and attack.

In very rare cases, even simple blood transfusions can lead to transfusion-associated GVHD, which is usually fatal. This is extremely unusual, but based on the same principle and occurs more in immunocompromised patients.

So could GVHD happen to patients of stem cell clinics?

In most cases the probable risk of GVHD seems very low in this context, especially with use of autologous (one’s own) stem cells, but it can get tricky if allogeneic cells are used. Also, one of the complicating factors here is that transient or low-level GVHD could occur in some cases with negative consequences but be very hard to detect.

Here are some takes on the hypothetical potential for GVHD with specific types of stem cell injections at clinics, listed roughly in increasing order of risk. Note that I’m not a physician and this post is not medical advice.

Fat “stem cells”

Fat stem cell preparations such as stromal vascular fraction (SVF) apparently contain some immune cells, but only a minority of the overall cell population. Also SVF is nearly always an autologous transplant anyway so these cells are unlikely to view their new home after injection elsewhere in the body as foreign.

Lab culture or contamination of these cells before transplant may lead them to be eliminated from the body more quickly, but in theory shouldn’t present a high risk of GVHD. Most stem cell clinics do not grow the SVF cells prior to use anyway.

Still, we cannot entirely rule out other kinds of immune issues from SVF injections. These cells do not belong outside of adipose tissue so injecting them into the bloodstream or tissues where they don’t belong could trigger immune issues, most often leading to rejection of the transplanted cells.

Bone marrow injections

Minimally-manipulated, autologous injections of bone marrow cells given at unproven stem cell clinics to patients should present a very low risk, most often zero, for GVHD.

A hypothetical risk could arise if the bone marrow cells were cultured before injection and/or otherwise altered in such a way that they recognized some “self” tissue as non-self, but it seems unlikely and most clinics in the US do not grow bone marrow cells before use anyway. In addition, if bone marrow cells are just injected into defined spaces like joints, GVHD becomes even less likely.

Allogeneic bone marrow injections, however, have substantial risk of GVHD. We just don’t see many clinics offering these.

Birth-related stem cells

Birth-related cells represent more a complex picture and at least a relatively higher risk of some kind of GVHD.

Amniotic or placental stem cells.

Let’s talk about amniotic and placental “stem cells” first since they’re simpler. They are used in an allogeneic fashion so in theory could lead to issues, but the cells are mostly not immune cells and so most of the cells cannot mount an immune response against a patient. The reason the risk is not entirely zero is that these cells/tissues have blood in them (placenta) or be contaminated with blood (amniotic) that is a mixture of baby’s and mom’s blood. There can also be some resident immune cells in the tissues. However, on a simple level it seems relatively unlikely there would be enough immune cell contamination to cause problems, but I’m not sure this has been studied.

The other potential risk-lowering factor here is that it appears that many preps of “stem cells” of this kind are actually dead cells or cell extracts. While this might be a good thing from a GVHD perspective, an IV infusion of a different person’s dead cells and debris could be problematic for the recipient in some ways including affecting the immune system.

It also means there’s little chance these preparations used at for-profit clinics could be effective for treating illnesses.

Umbilical cord cells.

The other main kind of perinatal “stem cells” that are popular these days at unproven clinics come from the umbilical cord. While Wharton’s Jelly cells are now sometimes used, mostly umbilical cord blood cells are the focus of clinic injections. Since these are immune cells from another person, they present some clear risk of GVHD, and there is a literature on this in PubMed.

In a for-profit unproven clinic setting there’s just not enough data to try to pin down the specifics of the risk here, but amongst the cells discussed in today’s post, these probably present the highest risk.

It’s also worth noting that many of the cells in unmatched allogeneic umbilical cord cell injections at clinics are likely to be killed by the recipient patient’s immune system lowering the chance of any actual benefit, although there is some debate about the possible immune stealthiness of these cells even in allogeneic setting.

Overall take-home

In a general sense, the relative risk of the cells in a stem cell injection turning against and attacking a patient’s cells and tissues leading to some kind of meaningful GVHD depends greatly on the type of cells being used and the care with which they were handled.

Disclaimer: this post is not meant as medical advice. Talk to your physician (I’m not an MD) before making medical decisions.

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