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Medical Minute 8-26: Healing Wounds With Your Own Skin Cells

By: Vanessa Welch Email
By: Vanessa Welch Email

Spending time with her grandchildren hasn't been easy for Karen Marshall.

"I have had so many times that I've been down because of infection, and that takes a while to clear up and everything," said Karen Marshall, Has CREST Syndrome.

Doctors diagnosed Karen with crest syndrome 10 years ago -- an autoimmune disorder that makes it difficult for her to heal. A paper cut took her nine months to close up. A deep leg wound took five years. After a MRSA infection exposed her tendons around her ankles, doctors made a recommendation.

"They say you can just continue doing what you're doing forever and ever or cut it off. I wouldn't accept it."

Instead, she found Doctor Evangelos Badiavas with the University of Miami Miller School of Medicine. He enrolled her in a study that takes stem cells from a patient's own body and uses them to treat their stubborn wounds.

"We have had patients who have not healed for more than 10 years and achieved full healing," said Evangelos V. Badiavas, Ph.D., M.D., University of Miami Miller School of Medicine.

The cells are applied directly to the skin and injected locally.

"The very bright green areas are bone marrow cells that are entering into the wounded area, and they're incorporating into the muscle tissue as you can see right here overlying some of the muscle."

The hope is to achieve complete regeneration of the tissue.

"So that I, you know, don't feel like I'm going to be like this forever.

The process could take more than a year.

For more information on other series produced by Ivanhoe Broadcast News contact John Cherry at (407) 691-1500, jcherry@ivanhoe.com.

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MEDICAL BREAKTHROUGHS - RESEARCH SUMMARY:

BACKGROUND: Limited scleroderma, or CREST syndrome, is a subtype of scleroderma -- a condition that means "hardened skin." Skin changes associated with CREST syndrome typically occur in the lower arms and legs and sometimes in the face and throat. CREST syndrome can also affect the digestive tract and can cause serious heart and lung disorders. There is no known cure for CREST syndrome. Treatments focus on managing symptoms and preventing serious complications. Sometimes, patient with this syndrome have a difficult time healing.
(SOURCE: Mayo Clinic)

WOUNDS THAT WON'T HEAL: Nearly 6 million Americans suffer from chronic wounds that fail to heal for months or even years. These wounds can be painful, disabling and lead to millions of amputations. Chronic wounds cost the U.S. health care system about $20 billion a year.
(SOURCE: University of Miami Miller School of Medicine)

STEM CELLS: Doctors at the University of Miami Miller School of Medicine are participating in a study that takes stem cells from a patient's own body and uses them to treat their stubborn wounds. Adult stem cells are becoming a more realistic option for treating wounds that are refusing to heal. Certain stem cells can be isolated from bone marrow and other tissues, such as adipose and skin tissue. Rapid regeneration of skin can be achieved after the transplantation of these cells. Stem cells can be obtained not only from the outside of the skin but also from local skin. Cell therapy is the transplantation of allogeneic cells to restore viability and function of deficient tissues. Some scholars believe that the plasticity of stem cells is a result of the cell fusion between adult stem cells and skin cells. Therefore, it is important to create an appropriate microenvironment, which will be the determining factor as to whether or not stem cells will survive and participate in regeneration and reparation of wounds.
(SOURCE: University of Miami Miller School of Medicine)

THE NEXT STEP: Researchers are already planning the next trial to test the use of donor bone marrow stem cells on the chronic wounds of patients whose own stem cells are likely compromised.
(SOURCE: University of Miami Miller School of Medicine)

FOR MORE INFORMATION, PLEASE CONTACT:
Omar Montejo, Media Relations
University of Miami Miller School of Medicine
(305) 243-5654
OMontejo@med.miami.edu

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THE FOLLOWING IS AN IN-DEPTH INTERVIEW WITH THE DOCTOR FROM THE STORY ABOVE:

Evangelos V. Badiavas, PhD, MD, Associate Professor of Dermatology & Cutaneous Surgery from the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine, discusses how using stem cells extracted from the patient’s own bone marrow can be administered to aid in the regeneration of tissues for people with chronic wounds.

Can you talk a little bit about how much excitement has come from the development of technology that can ultimately regenerate tissues?

Dr. Evangelos V. Badiavas: It is an exciting time, because there are diseases that presently have no treatment. We are thrilled to have the technology to regenerate tissues in an effort to cure these disorders. Furthermore, we could have the ability to change organs that are no longer functioning into ones that function normally. Other opportunities that this technology might be used in is fixing organs that were never working right from birth – ones that due to genetic defects never functioned properly. Perhaps, even by using some of the patient’s own cells, you may be able to fix that defect.

Can you discuss the severity of change in a normal person’s quality of life once they are experiencing symptoms such as those aforementioned?

Dr. Evangelos V. Badiavas: Persons with chronic wounds, are often debilitated. They had an active lifestyle prior to their wound, but because of an open wound that won’t heal, their life has become significantly altered. When patients reach the end stages, they have no evidence of healing. This isn’t the response that you would expect from someone who is in good health with normal circulation. The chance to give someone the ability to heal is a great advantage for them. They can return to a normal life. The interesting part about this is that the change is made with the use of all of their own cells. It’s not as though the entire body doesn’t have the ability to heal, it’s those cells that are present at that particular site that are diseased and improperly functioning. It is there that the tissue regeneration can’t take place.

Are there particular diseases that displays these symptoms?

Dr. Evangelos V. Badiavas: It is hard for people to believe that this can happen. In a variety of disorders including diabetes, patients who have peripheral artery disease with poor circulation – as well as myriad other disease,it is actually a total body effect. The effects involve many organs that people don’t normally assume. In that group of organs affected is the skin. Ultimately, the ability to heal is greatly altered. This type of process is actually quite common. Diabetics don’t heal as well as those who don’t have diabetes, and as your diabetes gets worse, your ability to heal gets worse.

Can this happen to anyone, young or older?

Dr. Evangelos V. Badiavas: It can happen to young people. We have treated patients in their 40’s.

How does the stem cell therapy work in order to give patients back their ability to regenerate tissues?

Dr. Evangelos V. Badiavas: There are a variety of stem cell sources throughout the body, but perhaps one of the richest areas is in the bone marrow. The bone marrow contains a number of stem cells as well as progenitor cells. Among these are all of the cells that make your blood, but in addition there are cells that make up blood vessels. These cells can be extracted, grown and cultured so they can be given to patients. They also have several specific features, one of which is that they tend to be younger cells. In a sense, they grow better, and they don’t seem to have some of the growth regeneration issues that are evident in the skin of patients suffering from chronic wounds. By taking those cells, and applying them to a specific area where they might be able to alter tissue regeneration locally, we believe that we have a treatment for patients who suffer from these deficiencies.

What did you do in particular for this patient that gave her back the ability to heal?

Dr. Evangelos V. Badiavas: We brought her into the hospital and extracted a certain amount of bone marrow. In some cases such as this one, the patient receives an administration of fresh bone marrow containing all of the cells extracted. In other patients, including this one as well, we receive the bone marrow, which we take into the lab, where they are furthermore cultured and grown so that we can have additional administrations for the patient without having to keep extracting bone marrow. There also may be an advantage to taking bone marrow cells into the laboratory, since we may be able to correct any total body defects that they may have. By nursing the cells in the lab, we are given the opportunity to grow and alter them so that when administered they can make the appropriate changes needed to regenerate tissue.

How are these cells administered to the patient?

Dr. Evangelos V. Badiavas: We actually directly apply them to the skin as well as injecting them locally. One of the amazing things about this project is that it appears as though that these cells are almost needed in that area. They are recruited to that site of injury. This is a finding that many of us have actually found throughout our research. Stem cells are actually recruited to areas of injury, almost as though the body calls them and stem cells know that they are required to repair that area. Perhaps in these patients this system of regeneration breaks down. What we are doing is bypassing that breakdown by bringing the cells directly to the area needed.

Can you just briefly discuss the difference between the benefits of administering stem cells via cultured bone marrow versus that of how the body works in repairing itself without stem cell application?

Dr. Evangelos V. Badiavas: There are probably several parts to it. One of which is the traffic jam – the cells in the body just can’t make it to where they want to go. It is not hard to understand that certain patients with circulation deficiencies have difficulties with getting cells to that particular site. We are able to deliver these cells and aid in the regeneration process for the reason that we are applying them directly to the problem area, and we are able to deliver them at a much higher dose. In a sense, the cells that were taken from your own body almost become like a drug, a medicine, a treatment if you will. It is because we can administer them to patients at what we call a pharmacological dose as opposed to a normal physiological dose. Having these cells administered in this sort of fashion will offer far greater results for patients.

Is this something that will perhaps put a spotlight on the field?

Dr. Evangelos V. Badiavas: We hope so. This is a field of medicine that is still in the early stages. Every step that we make and all of the progress that has come from our research is a significant step for the field in general. The majority of patients that require these methods of treatment are those that show a deficiency in their body’s ability to heal. When we do treat them, they do show evidence of healing. This is something that still needs further investigation and development, but at the same time it is something that we are all proud to be a part of.

Is this still in the clinical trial phase?

Dr. Evangelos V. Badiavas: Yes. This is still in the clinical trial phase and it is still evolving. At first, we looked at how we could deliver as many different types of cells from the extracted bone marrow (blood vessel progenitors, blood stem cells as well as other cells that are found in the bone marrow), but in the subsequent trials ahead we are focusing efforts on specific types of stem cells to see how they respond in different types of wounds.

Are all of these cells that are used in the healing process used solely from the patient’s stem cells?

Dr. Evangelos V. Badiavas: All of the cells that we have delivered thus far have come from the patient’s body alone. That is a good question, because what is possible is that if you have a disease that results in so many problems, does that mean that your stem cells may have some of those same problems. We have seen some evidence that stem cells taken from wound patients aren’t completely normal – they aren’t as fast or robust as those from a healthy college student. Perhaps it might be better to take stem cells from someone who is younger and healthier, and administer those cells to the patient. Moreover, there are some hurdles that must be considered. The most prominent being the notion that perhaps the patient’s body might reject someone else’s stem cells. Maybe these cells will only perform a repair process and then leave – it still may work. This is the reason that we are currently investigating different stem cells such as mesenchymal stem cells, which don’t produce a significant immune reaction and perhaps may suppress the immune system. We are hoping that cells from younger and healthier individuals can be implemented in the application of normal stem cells for the treatment of diseases without adverse effects on the immune system.

Is using other people’s stem cells to regenerate tissues in patients something that is being done in an effort to treat immune system deficiencies?

Dr. Evangelos V. Badiavas: Yes. This is something that is being done today.

Are stem cells similar to that of blood types for the reason that certain individuals might not be able to be recipients of certain donors?

Dr. Evangelos V. Badiavas: There are certain cells such as endothelial progenitor cells that make blood vessels. Those cells might be something that has to be typed (similar to that of blood types) when administering a transfusion because they do produce an immune reaction. There are some stem cells, nevertheless, that don’t appear to produce this sort of reaction. It seems as though some of these cells might be privileged in the way that they are not fully recognized by the immune system. In fact, there are some stem cells that display evidence of being cloaked from the immune system and perhaps even suppress it as a means to not being rejected.

How far away are you from completing this trial and having the FDA approve it?

Dr. Evangelos V. Badiavas: The trial that we are doing that involves various types of stem cells has been through the review process of the FDA. It is still an ongoing study. We have approval for an additional trial that will look at other people’s stem cells, and study how these cells are different than those of the patients. Again, we are looking at patients who have chronic wounds due to a variety of deficiencies, displaying no evidence of healing.

Are these patients who have a cut and show little to no evidence of healing within a span of weeks?

Dr. Evangelos V. Badiavas: It is actually patients who have no evidence of healing. In the current trial, we have had patients who have shown no evidence of healing for more than 10 years, and with this treatment show signs of complete tissue regeneration. That is the remarkable part about this. Another incredible aspect is that the patients healing process appears to be that of a normal individual and appears exceptionally durable. With other treatments, there are results that show closure of wounds, however, that closure is fragile and breaks down very easily. In the few patients that we have had participate in this trial, we have seen the wounds close and remain pretty durable.

How many patients have you seen thus far in the trial?

Dr. Evangelos V. Badiavas: Overall, we have looked at over a dozen patients, and are actively looking to recruit more so that we can further develop this method of treatment.

How do people interested in participating in the trial become involved?

Dr. Evangelos V. Badiavas: They can contact me at the University of Miami’s Stem Cell Research Institute and Department of Dermatology.


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