Research

Angiogenesis Demystified

Angiogenesis.

At first glance, it can seem like an intimidating word. A lot of people may inadvertently find their eyes glazing over whenever they encounter medical terminology with more than a few syllables.

Angiogenesis forms blood vessels from existing blood vessels

But it’s well worth learning what this particular process is for anyone considering bone or tissue grafts, because the effectiveness of the entire procedure depends on angiogenesis.

In fact, as part of our efforts to create better cellular allografts, Burst Biologics has had to find ways to encourage angiogenesis. Read on to understand how the process works and why it matters.

What Exactly is Angiogenesis?

At a basic level, angiogenesis is simply the formation and development of new blood vessels. More precisely, it forms new capillary blood vessels from preexisting blood vessels.

If you’re a word nerd, you may find it helpful to consider the term based on its two roots:

  • Angio – blood vessel
  • Genesis – creation

In addition to angiogenesis, there’s vasculogenesis. This is a different but related process in which brand new blood vessels are formed from angioblasts (aka endothelial precursor cells). You’ll generally only see vasculogenesis in an embryo – by the time an individual reaches adulthood, the formation of new blood vessels occurs primarily through angiogenesis.

Why is Angiogenesis Important?

The reason you should care about angiogenesis is for its essential role in wound healing and bone formation. Yes, it’s actually needed in order for bone to form!

For example, in the case of a spinal fusion, there’s typically some kind of a gap between two vertebrae that needs to be filled in with natural bone. How does a physician make that happen?

Well, a bone graft like our BioBurst strip can help. When it’s placed in the cavity, the strip creates an osteoconductive matrix as a scaffold for new bone formation. However, just as important is the inclusion of powerful natural growth factors and cytokines. One of these is the VEGF, or vascular endothelial growth factor, a signal that tells the body to grow blood vessels in the area.

Angiogenesis matters because bone is a highly vascularized tissue that relies on the connection between bone cells and blood vessels in order to maintain skeletal integrity. If you have the ingredients in place for bone growth, but not for blood vessel formation, the procedure isn’t going to have the greatest impact.

Angiogenesis encourages blood vessel growth

And why are blood vessels so important? Ultimately, bone and tissue regeneration require angiogenesis – the formation of a functional microvascular network – because new blood vessels promote much-needed blood circulation to areas in the body that need nutrients. In our spinal fusion case, the affected area needs a lot of raw material to rebuild bone, and blood vessels make that possible.

Angiogenesis in Allografts

So, what does all this mean in plain English? It means that if you want an effective allograft, you need to consider whether the products you rely on induce the creation of new blood vessels.

When you consider effectiveness in biologic applications, speed is a big motivator. Fortunately, a process like angiogenesis can directly boost the speed of healing, because it creates more capillaries that allow more nutrients to be delivered within the same timeframe.

But that’s not all. As important as this specific process is, there’s another key point here, which is that bodily processes are interconnected. Like with digestion or respiration, the formation of bone (ie osteogenesis) doesn’t occur in a vacuum.

That’s why regenerative medicine products need angiogenesis as part of the bone consolidation process, and why it’s so important to continue researching ways of inducing it for healing.

Interested in learning more? We’ve recently released a new BioBurst Fluid research brochure that delves into BioBurst Fluid and its unique angiogenic properties, as well as the science behind angiogenesis.

Head on over to My BioPortal to grab a copy or ask your rep about it today!


Inside the Research Rotation Program at Burst

It’s not often you find something everyone can agree on.

After all, we live in a world of cat people versus dog people, vegetarians versus meat lovers, and even Mayweather versus McGregor.

But here at Burst Biologics, I couldn’t find anybody who wasn’t positively glowing with praise about our company’s research rotation program. In my talks with the company’s research Ph.Ds and lab technicians, it dawned on me how special this program really is.

Lab Techs Versus Research Ph.Ds

To understand why research rotation is such an important part of Burst Biologics, you need to understand the role of a lab technician.

We have several lab technicians who work in the laboratory every day, and unlike at other companies, all of our lab techs have at least a bachelor’s degree in science. Due to their qualifications, they’re responsible for several key job duties:

  1. Processing, manufacturing, and packaging the company’s products in a sterile environment.
  2. Validating processes.
  3. Ensuring all regulations are followed.
  4. Maintaining and cleaning the laboratory.
  5. Taking care of equipment.

The bulk of their work ultimately revolves around keeping up the lab and producing enough of each type of product to meet demand. As for the staff of research Ph.Ds, this group uses lab space to conduct assays and experiments for research and development.

Research laboratory vials

In most companies, the laboratory department is totally separate from research and development (R&D), but at Burst, the two departments intersect – and this is largely because of the research rotation program.

What is the Research Rotation Program?

Every six weeks, a lab tech will get one week of research duties, where they work closely with a Ph.D. During their research week, the lab tech will handle data analysis, take pictures of experiments, and cover other tasks that are commonly associated with the role of research assistant.

One of the company Ph.Ds, Dr. Trillitye Paullin, told me that there’s a 100 percent participation rate in research among our lab techs, likening the rotation to an internal internship. The lab techs not only get to do hands-on research work during their designated week, but they also get an intimate look at how the Ph.Ds approach their projects. They even get the opportunity to use cutting edge lab equipment like the MagPix on the job!

Research Experience Matters

In case it wasn’t clear yet, this opportunity is a big deal for someone who’s starting out in the science field. The lab techs explained that when you’re pursuing a bachelor’s in science, you have to be exceedingly lucky and talented to do research work under a professor.

According to the National Center for Education Statistics, the average student-faculty ratio for colleges is 18:1, a ratio that isn’t nearly small enough to allow professors to work closely with each and every one of their students.

This fact is particularly problematic for science majors, because it means that research opportunities in academia are limited – and a lack of research has implications for their futures. It calls to mind the old adage about needing experience to get a job, and needing a job to get experience: without having prior research under their belts, a lot of opportunities are closed off to aspiring professionals in science.

What the Lab Techs Say About Research Rotation

One of the lab techs told me that he’d had a year of work experience in another lab before coming to Burst Biologics. “My previous job didn’t give me great actual experience as far as what a lab tech does,” he said. “Burst is a great place to learn a lot as a lab tech, and research weeks are the weeks I look forward to most.”

Lab technician at work in research rotation

He wasn’t the only one excited about the chance to do research. Another lab tech told me, “I look forward to rotation. We get to be an actual collaborator with the Ph.Ds. They trust us and ask us for our advice and opinions, and we get to see what R&D is up to firsthand.”

Everyone agrees that the opportunity to do research is a great draw for our qualified lab technicians – even the ones that have moved on from Burst. Two of our lab techs already parlayed their on-the-job research experience into graduate school programs, including one at Boise State University and another at PA school in Montana.

We’re excited to see them bettering their education, and we certainly will be excited to welcome them back to the team after they graduate!

Breaking up the Routine

Aside from the value of gaining research experience, there’s another great reason for research rotation. The lab tech supervisor explained to me that although lab tech work is crucial, it can get repetitive. The lab tech’s job requires the precise implementation of specific processes on a daily basis.

Fortunately, research rotation switches things up for the lab techs, engaging their critical thinking skills and granting them greater perspective that they can take back to their regular role. Because it’s their job to actually manufacture our products, lab technicians can take what they learn in research and use it to improve procedural design and validation for product development.

So Happy Together

In the end, the research rotation program helps both sides. It’s important to integrate manufacturing and research to create new products that can be manufactured with efficacy. Integrating the two departments keeps everyone working on the same page, bouncing ideas off one another.

This arrangement is also great for the Ph.Ds. Conducting experiments involves a lot of moving parts, so if they can get help every week from a lab tech, that enables researchers to work on their papers, design new studies, and interpret the results of their experiments.

The research rotation program is just one more way that Burst Biologics sets itself apart. It’s not always easy to find the win-win – but we’re making it a priority to do just that.


Regenerative Medicine Solutions for the US Military

We’ve seen huge strides in regenerative medicine solutions over the past few decades. Thanks to the field’s groundbreaking gene, cell, and tissue-based therapies, countless people can now enjoy pain relief and restored functionality after injury or deterioration.

The pace of new discoveries in regenerative medicine is only accelerating, and Burst Biologics is proud to be a part of this progress, creating innovative new products that help consolidate bone, regenerate soft tissue, and more.

Of course, our work to date has focused on patients and physicians in the civilian world, but we’re excited to announce that we’ll also be conducting research on behalf of the military! Soon, our newest staff Ph.D. will begin applying for U.S. Department of Defense (DoD) grants related to gene and cellular therapy on behalf of Burst Biologics.

US soldiers benefit from regenerative medicine solutions

As a company, we have staff with close associations to the military, including our CEO Christopher Jones, a veteran who’s designated Burst Biologics as a veteran-owned business. That’s why this next step is meaningful for the company, both personally and professionally.

It’s inspiring to us that the research we do will end up saving lives and dramatically improving the quality of life of wounded soldiers.

Regeneration From the Wounds of War

It may have gone under your radar, but the US military has already taken note of the power of regenerative medicine.

In fact, the US Army has employed regenerative medicine solutions to help wounded service members over the last decade. This is partly thanks to an organization called AFIRM – the Armed Forces Institute of Regenerative Medicine – which helps develop advanced treatment options for injured servicemen and women.

Armed Forces Institute of Regenerative Medicine

It’s important to note the difference between treating civilian patients and active soldiers wounded in the line of duty. Many service members sustain unique tissue injuries and complications in combat due to bullets, shrapnel, and high-energy explosives. As a result, the damage that must be healed is far more extensive than in most civilian injuries.

War trauma often requires restoration of complex tissues involving a number of integrated cell types – in civilian patients, on the other hand, physicians can use regenerative medicine solutions for a targeted, localized function, such as mesenchymal stem cells in the spinal cord for bone growth.

The Emergence of New Regenerative Medicine Solutions

Obviously, there are serious challenges associated with treating wartime wounds, which is why organizations like AFIRM are so important. In conjunction with the research undertaken at a number of medical technology companies, AFIRM has already been able to successfully treat severely burned skin with some novel solutions:

  • Embrace. A stress-shielding surgical bandage that reduces scarring after surgical intervention.
  • ReCell. A “spray-on” skin designed for first or second degree burns.
  • StrataGraft. A durable skin substitute that will heal normally after application.

These particular skin healing innovations dramatically improve treatment effectiveness and make it possible for soldiers to recover without the need for donor sites. There have also been major advancements in other areas, such as hand and face transplantations, with further progress underway on vascular composite tissue allotransplantation, craniomaxillofacial reconstruction, and extremity injury treatment.  

Honoring US military servicemen and women

Ultimately, the goal is to fully heal anyone who’s been injured in battle, which includes both civilians and wounded soldiers. Regenerative medicine solutions come into play when conventional treatment options aren’t effective enough to restore lost functionality, form, and comfort.

Applying for DoD Grants

AFIRM is playing a key role in the revolution of regenerative medicine solutions for the military, because the Army doesn’t have the expertise or the budget to develop novel medical solutions on its own. Instead, the DoD defines projects that it wants to come to fruition and funds the research that makes them possible.

Sometimes, the DoD will pick just one organization to handle the research for a project – but in other instances, a massive project is broken down into different facets and shared among a handful of organizations based on their areas of expertise.

As a medical research company, Burst Biologics is committed to helping the military and our nation’s servicemen and women through pioneering biomedical research. Our next step is to look for DoD solicitations that we can fulfill and apply for grants. This will help cover the costs as we conduct research in-house today that will support the health and well-being of our troops tomorrow.

The Future of Regenerative Medicine Solutions

Regenerative medicine couldn’t have come at a better time. According to the Centers for Disease Control and Prevention, about half of all adults in the United States (117 million people) suffered from one or more chronic health conditions.

This is an alarming statistic, particularly because most treatments for chronic diseases today are simply palliative – they don’t do much to prevent or delay disease progression or the onset of complications.

While regenerative medicine is still a burgeoning field, there’s already evidence to suggest that it can address the underlying mechanisms and causes of disease, in a way that’s never been possible before.

Here are a few examples we’re likely to see soon:

  • Cell therapy targeting blood cancers and solid tumors.
  • Gene therapy for genetic diseases and chronic conditions.
  • Gene editing to modify the genetic material of a patient’s cells to cure a range of diseases all at once.

If there’s one key takeaway here, it’s that we should no longer think of regenerative medicine solutions merely as “the future.”

The future is here now, making a difference in the lives of civilians and service members – and Burst Biologics is proud to be among those ranks, rethinking and evolving science every day.


Why We Ditched DMSO: A Look at the Safety of Dimethyl Sulfoxide

Early in the summer of 2017, I traveled to Europe to explore the Scottish Highlands. With rolling hills and an ethereal mist hanging in the air, the Highlands are easily among the most beautiful landscapes in the world.

DMSO is like the Scotland landscape

But even though I loved visiting the Highlands, I couldn’t imagine actually living there.

Why? Because there’s a flip side to such natural beauty: it has to rain nearly every day to support that amount of greenery.    

And not just a light drizzle.

I’m talking about heavy, fierce rain that can turn a pleasant afternoon hike into a jaunt through a hurricane in about five minutes flat.

It quickly occurred to me that the natural beauty of the Highlands was a double edged sword. The benefit of breathtaking scenery was overshadowed, quite literally, by nearly perpetual dark clouds and rain.

The DMSO Double Edged Sword

At Burst Biologics, we see a lot of double edged swords throughout science and medicine: Drugs can treat all kinds of conditions, but they also cause potential side effects. Surgeries carry the risk of possible complications, even as they give patients a new lease on life. Ultimately, it’s hard to get the good without a risk of the bad.

That’s probably why, in the world of regenerative medicine, it’s widely accepted that the cryoprotective agent (CPA) known as dimethyl sulfoxide (DMSO) is a necessary evil for cryopreserving graft sources prior to infusion in patients.

Many physicians simply accept DMSO as the “bad edge” of a double edged sword, with the “good edge” being the many benefits that patients enjoy with stem cell transplantation.

But this chemical can be more dangerous than doctors give it credit for.

A Brief History of DMSO

Dimethyl sulfoxide is a colorless liquid discovered in 19th century Germany as a byproduct of wood pulp when producing paper. One of its most notable properties is its ability to permeate across cell membranes. This quickly proved useful for dermatological conditions like skin inflammation or scleroderma.

DMSO is a byproduct of paper production

The year 1959 marked the first trial of DMSO usage to prevent freezing damage to living cells. Later, in 1978, DMSO received FDA approval for treating interstitial cystitis (aka chronic bladder pain).

However, all these decades later in 2017, the chemical is still only approved by the FDA for that single function. There have been rumblings about DMSO’s possible use in cancer treatment as well, but according to the Memorial Sloan Kettering Cancer Center, there are still lingering concerns over potential toxicities in DMSO. These concerns should – and do – spill over into DMSO’s use as a cryoprotectant.

Cell Preserver or Cell Killer?

On the positive side, DMSO has the ability to permeate across cell membranes, allowing it to inhibit intracellular ice formation and prevent injury in stem cell freezing. It’s also soluble in both aqueous and organic media, making it extremely useful both in the lab and in clinical applications.

But even with all these great properties, DMSO has its drawbacks. The chemical is associated with possible toxicity and a range of serious side effects, and we also know that prolonged exposure to dimethyl sulfoxide directly impacts cellular function and growth.

In fact, one of our molecular biologists explained that she uses DMSO to preserve cell lines for research, but once she’s done thawing cells, she gets rid of the DMSO as soon as possible. She’s learned from experience how quickly it kills her research cells. The same effect can occur in a clinical setting: once cells begin to thaw, they are susceptible to the cytotoxic effects of dimethyl sulfoxide.

So, with all this in mind, how exactly does this chemical affect patients in the real world?

Adverse Reactions From DMSO

As common as DMSO is as a cryoprotectant agent, there’s still a significant number of potential side effects and adverse reactions associated with the chemical. That’s why we made it a priority to completely eliminate DMSO from our products.

Here’s a brief look at the many adverse reactions (ARs) recorded after transplantation of hematopoietic stem cells in patients, as compiled in the study “Hematopoietic SCT with cryopreserved grafts” by Z Shu, S Heimfeld, and D Gao.

Types of ARs from DMSO:

  • Allergy. DMSO can induce a release of histamine. Common allergic reactions include flushing, rash, and edema.
  • Gastrointestinal. Affecting the limbic-hypothalamic pathways, DMSO can result in symptoms like nausea, abdominal pain, and emesis.
  • Renal. The incidence of kidney-related ARs is comparatively low, but includes symptoms like hemoglobinuria, proteinuria, and urine incontinence.
  • Cardiovascular. Symptoms include hypertension, arrhythmias, tachycardia, shock, cardiac arrest, and seizure.
  • Neurological. Symptoms include bilateral thalamic infarction, blurred vision, severe encephalopathy, cognition, muscle weakness, and numbness.
  • Hepatic. Symptoms include progressive jaundice.

As serious as these conditions are, this is only a partial list of the identified ARs related to DMSO, based on many studies centered around the physiological role of the chemical in ARs, from neurotoxic reactions to shock.

Studies also show that the adverse effects are cumulative. Patients receiving multi-dose therapies containing DMSO may suffer progressively more severe symptoms over time.

Even more worrisome, the scientific community doesn’t actually have a lot of data to suggest what effects the chemical may have on patients long-term. That’s why it’s problematic to inject people with the chemical – in the long run, we have no idea what may happen.

Now, to be fair, not all adverse reactions (ARs) are solely attributable to DMSO itself. In any allograft or stem cell transplantation procedure, there are many components involved. Some of these factors, such as dead cell debris after thaw or the low temperature of infused products, can also lead to ARs.

But much of the concern does lie with DMSO itself, as illuminated by a documented causal relationship between DMSO and adverse reactions. That’s why there’s been a concerted effort in the industry to remove or reduce DMSO from cryopreserved products.

What to do About DMSO

If we know that DMSO has the potential to be harmful to patients, the next question is, what do we do with that information? After all, cryopreservation is still a necessity if we want patients to enjoy the benefits of allografts and stem cell transplantation.

Well, you can deal with this problem in a few ways. One of the most common is DMSO removal through centrifugation right before delivery to the patient.

3D Model of DMSO Molecule

This is certainly a positive for many patients, but it still doesn’t fully resolve the problem. Aside from adding extra steps to the transplantation process, spinning down the product in a centrifuge still leaves trace amounts of DMSO, enough to trigger an AR in those who are sensitive to the chemical.

Plus, in the time it takes to thaw, spin, and resuspend the product, there’s also ample opportunity for cell death.

So, what else can be done? Here are four other widely discussed strategies for minimizing adverse reactions to dimethyl sulfoxide in cryopreserved grafts:

  • Reducing overall DMSO concentration
  • Administering medication before and after transplantation
  • Optimizing the infusion procedure
  • Using alternative CPAs for cryopreservation

The first three solutions hold some promise, but the bottom line is, nothing is safer than simply avoiding DMSO altogether.

A True DMSO Alternative

At Burst Biologics, we chose the fourth option: adopting a non-toxic DMSO alternative for cryopreservation in our BioBurst cellular allograft products. We developed the Progenokine Process to preserve product integrity and address the potentially harmful agent of DMSO in our cryopreservation media.

Our own lab research has demonstrated the efficacy of this DMSO-free stem cell cryopreservation medium, which enlists USP grade non-toxic ingredients. Ultimately, the products do their job well without even a hint of dimethyl sulfoxide.

In finding a quality DMSO alternative for our BioBurst products, Burst Biologics has taken a major step forward in improving the safety of regenerative medicine. While there’s still work to do, we’re proud to be moving forward on innovative new solutions that help people live healthier, more fulfilling lives.

Sources:

  1. Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion
  2. Dimethyl Sulfoxide-Induced Toxicity in Cord Blood Stem Cell Transplantation: Report of Three Cases and Review of the Literature
  3. Clinical Toxicity of Cryopreserved Bone Marrow Graft Infusion

Got Stem Cells on the Brain?

As we’ve mentioned before, Burst Biologics has its own lab and a staff of Ph.Ds working to make contributions to science, but we also follow what’s going on in our industry as a whole. There have been some amazing developments in the fields of biology and regenerative medicine over the last few years, like this exciting new study released in Stem Cell Journal on July 11 about the use of neural stem cells in the brain.

We thought the study was so interesting that we wanted to pass it along to you! 

Moving Neural Stem Cells

Human neural stem cells

Picture a big brick building on the riverfront. You walk up to it and notice that one corner of the building has suffered some serious water damage, probably from a recent flood. To fix the problem, you’ll have to redo some of the masonry, and in order to do that, you need to get bricks to the construction site.

Unfortunately, moving bricks poses a bit of a challenge. Access to the site by land is restricted, and the water is flowing the wrong way for an easy trip by boat. As you ponder the situation, you quickly realize that it doesn’t matter how well-made your bricks are – they won’t do any good unless you can get them where they’re needed.

In the case of the study “Electrical Guidance of Human Stem Cells in the Rat Brain,” researchers were faced with a similar dilemma: how do you get viable neural stem cells to the part of the brain where they can actually be useful in repairing damaged brain tissue?

An Electric Idea

What these scientists found was that they could mobilize and guide neural stem cells in the brain in vivo through electric stimulation.

They transplanted human neural stem cells (hNSCs) into the rostral migration stream (RMS). This pathway is a mechanism in the brain unique to certain animals, including rodents, rabbits, and monkeys. (Humans have one too, but it’s nowhere near as substantial as in other mammals, particularly rats.)

Along this special migratory route, neurons can differentiate once they reach the olfactory bulb (OB). However, with the application of an electric field, transplanted cells migrated against the endogenous cues. In other words, instead of going toward the OB, these neural stem cells moved deeper into the brain.

Intermittent electrical current drives human neural stem cells

In the case of our brick building scenario, it would be like moving bricks to the construction site against a river current. You’d obviously need a special kind of boat to get there, and any effort would pose its own challenges. For example, if you used an electric-powered speedboat, you would have to confront the other unique difficulty in this case, which is working safely with electricity.

The reality is, you don’t want to introduce a direct current electric field to the brain. This would induce a dangerous, potentially brain-frying Joule effect – and we doubt these rats did anything to deserve the electric chair!

As an alternative, the researchers devised an intermittent electric field technique that minimized the detrimental effects and still managed to guide the migration of hNSCs and maintain cell viability. With this strategy in place, no animals suffered seizures or other obvious complications from the electric fields.

What Researchers Found

The ultimate results of the study were well worth noting. In looking at the rat brains at three weeks and again at four months after the electrical stimulation, researchers saw that NSCs had migrated from the injection site to the lateral ventricle (LV) region and the contralateral hemisphere of the brain, against intrinsic guidance mechanisms. What’s more, the effect of the electric stimulation continued to work even after the stimulation stopped!

Obviously, there’s a lot more to this study than we can delve into here, but the fundamental idea behind it is fascinating to consider. There may be profound implications for healing brain damage and reversing degenerative brain conditions in humans.

It also goes to show that there’s nothing more exciting than thinking up novel solutions to problems that have confounded scientists in the past, especially as new technology becomes available.

As our lab techs and researchers approach new challenges, these are the kinds of stories that inspire us – and we hope they inspire you too!


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

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 

What is Regenerative Medicine Today?

Prometheus regenerating liver

We all remember Prometheus.

As you’ve probably heard us mention a time or two, Burst Biologics is in the business of regenerative medicine – and yes, it’s as cool as it sounds!

But what does regenerative medicine mean?

At its core, it’s all about helping human cells, tissues, and organs work properly. This branch of medicine focuses on the way cells live and function every day.

Compared to the whole of medicine, this is one field that’s quite new. However, forms of regenerative medicine have been practiced for more than 1000 years, and were acknowledged conceptually even in Ancient Greece. Remember Prometheus and his regenerating liver?

Of course, what we think of as regenerative medicine today is closely associated with the emergence of tissue engineering back in the late 1980s. It’s all based on the way cells work.  

The Magical Regenerating Cell

You have trillions of cells in your body, and they’re constantly regenerating. That’s the basic explanation for why you can donate blood, get a haircut, or heal from a broken bone.

Some types of cells replace themselves quickly, like the stomach cell’s two to nine day lifespan. Others last much longer, like the four month renewal rate for red blood cells.

But in any case, the concept of regenerative medicine hinges on this idea of regenerating cells.

Defining Regenerative Medicinecells can be replaced or regenerate

So, to better understand regenerative medicine, we need to consider what would happen if a group of cells in your body weren’t operating at their best. Conceptually, what could we do to fix that problem?

From the purview of regenerative medicine, it comes down to two general remedies.

 

Replacement

One clear solution is to replace the deficient cells or tissues with healthy ones. That’s essentially what an organ transplant is. If you have a failing kidney, swapping it out for a new one can rapidly restore functionality.

Replacement can be difficult, expensive, and invasive – but sometimes, it’s the only recourse available to patients with serious damage to their tissue or organs. With regenerative medicine, it’s possible to grow the new tissue that’s needed for replacement.

Regeneration

Another option is to regenerate the tissues and encourage self-healing. With this approach, you’re simply helping the body do what it normally could do, kind of like filling up the gas tank in a car that’s stalling.

One of our products is a fluid that aids and supports various mechanisms which encourage bone consolidation. Obviously, the body already knows how to heal bones, but this product aids in regulating the micro-environment to be one that encourages bone consolidation so that patients recover more quickly.

If you were to see what’s happening at a cellular level, you’d notice signaling molecules like growth factors and cytokines swooping onto the scene of an injury. These cytokines interact with cell receptors in local host cells, and can trigger a response indicative of wound healing. Basically, almost as if leading by example, these healthier cells demonstrate the way the host cells should be working, encouraging them to get back to their former, healthy selves.

Cells Themselves

The field of regenerative medicine relies heavily on advances in tissue engineering, and exemplifies plausible use cases for cellular and a-cellular allografts. But you’ve probably heard a good deal of talk about “stem cells”, and wonder how that plays a part. A good way to think of regenerative medicine is as if it’s a company, in a thriving economy. This one company is made up of different departments, and within those departments are different job descriptions and different individuals filling them.

The focus for regenerative medicine has been on “stem cells”, here at Burst Biologics we believe that’s not the best way to look at regenerative medicine. It’s so much more than that. Instead, try to think of stem cells as a single worker, in a single department, of a whole company. Yes, it does its part. Yes, it makes the whole team complete. But the rest of the team isn’t relying on the existence of that one worker to do their own jobs. 

The Future of Regenerative Medicine

The potential applications of regenerative medicine are truly profound. With tissue engineering and regenerative medicine products, physicians have the building blocks they need to change, repair, and grow damaged tissue in patients.

Previously impossible treatments are theoretically possible using regenerative medicine, reversing the effects of aging, organ failure, chronic wounds, and lifestyle diseases. The future of regenerative medicine – and the medical field as a whole – has never been brighter!

 

 


Here’s Why We Love Signaling Molecules

Cells are a lot like people: they have different jobs to do, and they need to work together to get them done. But rather than communicate using text messages or video chats, cells rely on chemical messengers called signaling molecules.

Here at Burst Biologics, we make a big deal about signaling molecules. Cell phone communicationThat’s because biologic products without functional signaling molecules are like cell phones without a cell signal – they just don’t work.

To understand the need for signaling molecules like growth factors and cytokines in regenerative medicine, let’s take a closer look at how signaling molecules operate at the cellular level.

Signaled and Delivered

All multicellular organisms – including plants and animals – rely on the interactions among cells in order to survive. One great example of cell communication is the hormone insulin, which springs into action to clear the sugar from your bloodstream after eating.  

But how does this signaling stuff work, exactly?

Well, when your body needs something to happen, one of your cells will produce a signaling molecule (or ligand). This heads to a target cell and makes it do its job. The interaction between cells can take place over all kinds of distances:

  • Signaling molecules diagramDirect cell-cell communication (adjacent distances): Sends the signaling molecule through gap junctions between touching cells, like one person whispering in another person’s ear.
  • Autocrine (to self): Sends the signaling molecule to self, like someone who writes a note on their own hand.
  • Paracrine (short distances): Sends the signaling molecule locally, like someone passing along a note to a friend.
  • Endocrine (long distances): Sends the signaling molecule across the whole body, like shipping a message to a friend by postal service.

With so many different cells, there are a wide variety of signaling molecules that interact with them across a range of distances. And just like certain keys can only fit certain locks, the incoming signaling molecule must be the right fit for receptors on a cell’s surface or within the cell.

Only then can a cellular response take place.

The Signaling Molecule Cytokine’s Job

One of the most important classes of signaling molecules is the cytokine, which plays an essential role in inflammation and immunity.

Cell receptor for signaling moleculesMany diseases occur when there’s some defect in the process between receiving a signaling molecule and generating a cell response. Sometimes, the body just isn’t equipped to do it anymore. In our regenerative medicine products, it’s the newly introduced cellular derived molecules that come to the rescue – they carry signaling cues that guide the receptive cells in your body to heal, grow, or change. It’s a pretty incredible process!

Burst Biologics products feature some key cytokines, including the interleukins IL-1beta, IL-2, IL-6, and IL-10. These are autocrine and paracrine in nature, which means they are sent and received by the same cell or wander to nearby cells.

When interleukins and growth factors like these are introduced in a medical procedure, they help inform the target cells on how to do their jobs better. This is a potent avenue in medicine, and we’re excited to be on the cutting edge!

Better With Progenokine

Clearly, regenerative medicine and biologics wouldn’t be the same without signaling molecules. That’s why we’re proud of our patent pending Progenokine Process for preserving the signaling molecules in our products.

The methodology we follow ensures that our products have the greatest possible impact for patients. We wouldn’t have it any other way.

To learn more about our products containing signaling molecules, visit our products page!


BioBurst Fluid: Latest Clinical Study Underway

BioBurst Fluid and Microscope

Exciting news for Burst Biologics as we’ve secured approval for our latest clinical study focusing on challenging foot and ankle surgery patients using BioBurst Fluid. This particular clinical study framework was created widely in order to evaluate complex surgeries in challenging patient populations.

Most people will suffer from some degree of foot or ankle problems during their lifetime. Many times, those who are in need of surgery have endured long periods of debilitating pain and disability.  Because the foot and ankle have to bear the weight of the entire body, bone grafts used for arthrodesis or correction must heal quickly and completely. We believe this registry will demonstrate BioBurst Fluid’s ability to jump start the vascular process needed in bone formation.

We had the pleasure of sitting down with Dr. Burk, (foot and ankle surgeon)  to speak on behalf of BioBurst Fluid. Dr. Burk stated, “Complex procedures where surgical intervention is needed, often requires a jumpstart to facilitate the bone formation process needed to heal. Products like BioBurst Fluid give physicians like me a sophisticated and much-needed tool to address these patients.”

 

 

 

 

 

 

 

 

 

 

 

 

 

View this story on Newswire by clicking here.

To find out more on this prospective multicenter clinical study please visit: https://clinicaltrials.gov

Want more? Check out our last blog post.