A “Mismatch” Made in Heaven: Avoiding Graft-Versus-Host Disease (GvHD) With UCB

on 07.19.2017 / by Daniel Thrasher / 2 comments in Research, Thoughts

Matches aren’t just for online dating.

A Match Enjoying the Beach

In regenerative cell mediated therapy, you’re also looking for a certain type of match. But rather than long walks on the beach or a shared affinity for Jimmy Buffett tunes, you’re specifically seeking compatibility between the donor and recipient’s human leukocyte antigen (HLA) markers.

In many prominent regenerative medicine treatments, an imperfect HLA match means a high likelihood of developing graft-versus-host disease (GvHD) or suffering from a tissue rejection event. These are essentially two sides of the same coin:

  1. In GvHD, a certain population of the transplanted cells thinks your body is a foreign threat and attacks it.
  2. With tissue rejection, your body thinks the transplanted cells are a foreign threat and attacks them.

Now, because Burst Biologics uses umbilical cord blood as a source, our products don’t elicit such a response. But in regenerative therapy generally, an imperfect match could eventually interfere with the success of your treatment and lead to a host of side effects and complications.

GvHD manifests in one or more parts of the body – such as the skin, eyes, gut, and lungs – and occurs in two main forms:

Acute (aGvHD). Sudden onset, short-term condition with flu-like symptoms, such as fever, nausea, and irritated skin.  

Chronic (cGvHD). An autoimmune condition resembling lupus. Symptoms include dry mouth, shortness of breath, difficulty swallowing, muscle weakness, vision trouble, and abdominal swelling.

There’s a wide range in the severity of GvHD cases. Some patients experience nothing more than a mild rash, while others battle life-threatening symptoms due to GvHD.

In most cases, doctors will use immunosuppressant drugs to treat the condition. By tamping down the immune response, the body can sometimes power through the getting-to-know-you phase of a cellular allograft or replacement organ.

Unfortunately, this doesn’t always work.

There are times when a bad match starts to cause dangerous symptoms. That’s why it’s risky to rely on treatment after the fact to deal with GvHD. The better way is to help patients avoid GvHD in the first place.

You can do this by deriving cells from a source that doesn’t require doctors to play “matchmaker” with donor and recipient HLA markers: umbilical cord blood.

Matches Are Overrated

Generally, when doctors talk about regenerative medicine, they think of bone marrow. Over the years, that’s become the de facto source of mesenchymal derived stem cells to use in treating a range of diseases and disorders.

Bone marrowBut even though it’s widely known that mesenchymal stem cells have an immunomodulatory effect on immune cells, there are still a few key challenges in relying on bone marrow as a stem cell source.

First, as donor age increases, the efficacy of bone marrow derived stem cells declines. You don’t want to risk complications for a transplant that has little chance of actually doing what it’s supposed to do!

Second, aspiration of bone marrow is invasive, which makes it more difficult to depend on as a widespread source for stem cells.

Third, and perhaps most significantly, bone marrow derived stem cells require a virtually perfect match if you want to avoid graft-versus-host disease or a tissue rejection event.

That’s where umbilical cord blood (UCB) cells come in. Because they have an age of just nine months, UCB cells have underdeveloped HLA markers, so you don’t need a close match with UCB cells to avoid the dreaded immune response.

Because UCB mismatches are widely tolerated in patients, it’s possible for patients to use umbilical cord blood derived stem cells and their signaling molecules to enjoy a greatly reduced risk of GvHD or a tissue rejection event.

To see the potential immune response to UCB cells for ourselves, we actually conducted a mixed lymphocyte reaction study in our own laboratory.

A Burst Biologics Study

For our study, we took venous blood from three healthy adult volunteers, and then we treated each sample with cells from three separate BioBurst Fluid UCB donors, for a total of nine different combinations. This ensured a high likelihood of HLA mismatch, the very environment where graft-versus-host disease conditions should thrive.

Graft-versus-host disease (GvHD) mixed lymphocyte reaction study

After six days of co-culture incubation, we measured the lymphocyte proliferation. Our finding was that BioBurst Fluid does not cause an immune response, due to a lack of peripheral blood lymphocyte proliferation increase. In other words, we’ve seen no evidence of graft-versus-host disease developing from BioBurst UCB cells in our studies.

Of course, the lab and the real world are two different realms, so along with this internal study, we established an independent adverse event reporting database for our BioBurst products. To date, we’ve had zero incident reports of graft-versus-host disease or tissue graft rejection events.

Feel free to see the results of our study – BioBurst Fluid Cellular Allograft Does Not Elicit an Immune Response in Mixed Lymphocyte Reaction – posted in the BioPortal on our website.  

Further Research on UCB Safety

Of course, you don’t have to just take our word for it! This study conducted by Rajni Vyas et al in 2014 also found that unmatched allogeneic umbilical cord blood mononuclear cell transplantations didn’t elicit an immune response in allograft recipients.

There were some side effects reported, such as mild fever and headache, but “no GvHD or serious adverse effects were observed.” The haematological and biochemical parameters remained within the normal range, indicating a lack of immune response.

In a nutshell, these studies – along with countless patient cases – demonstrate that you can use minimally matched cell populations  from umbilical cord blood in transplant recipients with a minimal incidence of GvHD.

What’s more, this is achieved without the need for immunosuppressive therapy. BioBurst patients routinely benefit from the growth factor production and multipotency of UCB mononuclear cells, all while minimizing the risk of developing GvHD.

UCB derived cells also have an immune modulating activity, as described in this 2017 study. As an innate property, immunomodulation adds one additional layer of protection against patients developing GvHD or experiencing a graft tissue rejection event, while also serving as a potential solution for treating aGvHD after allogeneic tissue transplantation.

Minimizing GvHD

The bottom line is, matches aren’t all they’re cracked up to be. Umbilical cord blood derived stem cells are likely safer than the more commonly used bone marrow stem cells, and it’s because UCB derived cells possess underdeveloped HLA markers that are more unlikely to trigger an immune response.

It’s also important to remember that with BioBurst, your body isn’t trying to adjust to a permanent new crop of cells. Instead, the product features many signaling molecules and growth factors – messengers who arrive on the scene and tell your body to do its job. As long as the body doesn’t react with GvHD over that short initial time frame,  it’s possible to get all the benefits of a cellular allograft without the complications.  

That’s what the facts bear out about UCB derived cells in general, but we make the cellular allograft even safer (and more effective) with our Progenokine Process. This patent pending tissue processing methodology eliminates the unwanted components of umbilical cord blood samples, leaving behind only the desirable cell population, growth factors, and signaling molecules.

Ultimately, if you’re looking to avoid graft-versus-host disease, BioBurst products are a great choice. We’ve designed to reduce GvHD to a thing of the past.

Sources:

  1. Clinical safety in using unmatched allogeneic umbilical cord blood mononuclear cells transplantations in non-haematopoietic degenerative conditions
  2. Immunomodulatory function of whole human umbilical cord derived mesenchymal stem cells
  3. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells
  4. (Our own study) BioBurst Fluid cellular allograft does not elicit an immune response in vitro 
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2 comments on “A “Mismatch” Made in Heaven: Avoiding Graft-Versus-Host Disease (GvHD) With UCB

    1. Burst Biologics |

      It was great having you at our headquarters. We are glad you enjoyed your visit and that it was informative. Thanks for visiting us! -Burst Biologics.

      Reply

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