Colton’s walking after stem cell therapy for cerebral palsy in Panama

Colton is planning on coming to Panama for follow-up treatment later this year. Here is a video of him walking from June 2015.

And here was Colton in 2014 about one year prior to the video above. This video was taken a year after his first treatments in 2013.

To keep up with Colton’s progress on Facebook, please visit: https://www.facebook.com/ColtonMittmanFundraiser

Stem cell treatment in Panama shows signs of hope for local Belle Fourche boy

By Karla J. Flack, Black Hills Pioneer

James Habeck and his mother Melissa

James Habeck and his mother Melissa

BELLE FOURCHE — Three-year old James Habeck and his family have returned from a medical trip to Panama. His mother Melissa Habeck said they are noticing signs of improvement as a result of the stem cell treatment James received at the Stem Cell Institute in Panama City, Panama.

Treatment is hoped to provide James with relief from some of the complications caused by his cerebral palsy and allow him to do things a toddler would normally be able to do such as talk, sit-up, walk, turn himself over in bed at night so he would have fewer sleeping issues, and use his hands and feet. Some with James’ condition have tight muscles, but James’ muscles are just limp.

Medical professionals told Melissa that the new stem cells would live actively in James for six months. During those six months of cell life, whatever James learns and the strength he gains should remain.

The Habecks returned to Belle Fourche June 7 and shortly thereafter James’ extensive line-up of therapy treatments began. He is on a fast track of learning and is currently undergoing speech, occupational, and physical therapies in both Rapid City and Belle Fourche.

This week he was fitted for a wheelchair and evaluated to see if an augmented and alternative communication device could help him communicate. If he can train his eyes to look at a particular item on the device his family will know what he is trying to communicate to them.

“They feel like he is stuck in his body, and that it is possible; he understands 75 percent of what I say to him,” Melissa said.
The Hebeck’s trip began May 31 and entailed an hour flight to Denver and six hours from Denver to Panama. James had never flown but he did well with the flights.

Melissa asked doctors why hospitals in the U.S. don’t offer the treatment James needs. The answer was FDA (Food and Drug Administration) regulations.

A Southlake, Texas, center recently opened. The extent of services offered is not being released at this time. [Note: This statement is not accurate. The Riordan-McKenna Institute in Southlake, Texas treats orthopedic conditions such as knee injuries and arthritis and rotator cuff injuries with a combination of bone marrow aspirate concentrate and AlphaGEMS amniotic membrane product. More information can be found at www.rmiclinic.com]

The Habecks met an athletic coach who was receiving stem cell treatment in Panama for multiple sclerosis. He said he was walking with a walker prior to his treatments. A filming crew was with him documenting his progress as he no longer has to use a walker after undergoing multiple stem cell treatments.

Melissa said staff at the Stem Cell Institute said a number of autistic patients come there for treatment. Heart failure, osteoarthritis, rheumatoid arthritis, spinal cord injury, and autoimmune diseases are also treated at the institute.
James had stem cells that were extracted from donated umbilical cords injected intravenously into his arms. The injections went fine some days but other days were problematic because his veins would rupture and the medical team would have to find a new vein. Melissa said by the end of the week both her and James were crying, but the staff was excellent in dealing with it.

“They were using a butterfly needle to access the veins but collapsing veins were still an issue and James was getting tired of getting poked with needles,” she said.

Melissa said she has been in contact with individuals who tried stem cell treatments that were not successful. She said people who had their own cells taken and then transferred back into their bodies told her their treatments were unsuccessful. She also said some who had gone to other countries and did the spinal stem cell procedures said those results weren’t positive. Melissa said she feels very positive about James’ treatment.

He has a special walker that he can use if someone pushes it for him.

“He took off by himself in his walker after treatment,” Melissa said.

He has also started trying to use his arms and legs to stabilize himself. He has more neck control and is trying to use his neck to raise his head. He has also shown improvement in efforts to gain eye contact with those who are talking to him. He has to fight for control as his eyes both stray separate ways.

Melissa said that when James was younger he tried to walk but then stopped trying; then he tried to sit. She was told that often times people with cerebral palsy have to abandon one thing to learn something else. Treatment will hopefully allow for a number of items to be learned and motor skills to be tackled simultaneously.

“He cried when they took the iPad from his sight on the plane and when the augmented and alternative communication device was taken from him,” Melissa said. This type of expression in connection with wanting something has not been something he was able to do in the past. She was happy he cried to have it back.

The Belle Fourche community rallied around the Habecks with a fundraiser March 22 wherein $20,000 was raised for James to have the stem cell treatment. Belle Fourche Police Chief Scott Jones and Belle Fourche Fire Chief Kip Marshall were taped to a building while raising funds and businesses donated door prizes. The Naja Shriners clowns helped raise funds Danielle Butler, James’ caregiver, organized the fundraiser. Many people joined together to help James. Melissa said she couldn’t believe it when it became possible for them to go for treatment.

Update on Glenburn Boy Who Underwent Stem Cell Therapy for Autism in Panama

 

JUN 8, 20155:54 PM EDT
By JOY HOLLOWELL

In 2009, an 8-year old Glenburn boy became the first child in Maine, and one of less than a hundred nationwide, to undergo stem cell therapy to treat his autism.

TV5 has followed the journey of Kenneth Kelley as he travelled to Panama for treatments.

It’s been about two years since his last transfusion.

Joy Hollowell checked in with the now 14-year old to see how he’s doing.
====
Like most brothers, 16-year old Philip and 14-year old Kenneth Kelley enjoy challenging each other on video games.

“Who is better?

Kenneth points to Philip

Typical teenager is how most would describe Kenneth…something his parents couldn’t be happier to hear.

Kenneth was diagnosed with autism when he was two.

“Many reputable people told us that he should be put in an institution,” explains Donald Kelley, Kenneth’s father. “And that just made us more determined to find a cure for him. We knew there was one out there somewhere, there had to be.”

Like many parents of autistic kids, Donald and Marty Kelley went to numerous doctors and tried countless treatments, including installing a hyperbaric chamber inside their home.

They had read about stem cell therapy. but the clinic was in Panama, and it was still a relatively new therapy.

“Seeing doctors who tell you things that finally after a while you meeting everybody and you say to yourself, well yeah, OK, yeah, I’ve heard this before,” says Donald Kelley, expressing his frustration.

The Kelleys would spend the next two years researching stem cell therapy for autism, including visiting the clinic in Costa Rica.

“This was different,” says Donald Kelley, “this was totally different.”

Kenneth underwent his first cord blood infusion at the age of 8. That very next morning, The Kelleys say they saw a difference. Within a year, Kenneth was reading and communicating. He went back five more times, until the age of 12.

“The improvements that we saw with Kenneth were amazing,” says his father. “To see your child become you know, enjoying life.”

“Before stem cells, he was just off the charts most of the time,” says Kenneth’s brother, Philip. “Screaming, kicking. I don’t remember him ever actually having a conversation with me. He’s gone from more of a person that I had to take care of to a friend.”

8-year old Caroline calls her big brother a dolphin.

“because he’s very playful and he’s very nice and intelligent,” she explains.

“It was a true blessing that he got as far as he did,” says Donald Kelley. “And that he’s where he is today.”
+++
The Kelleys say for now, Kenneth is done with treatments. However, they would consider going back, depending upon their son’s progression.

They tell other parents of autistic kids to never give up.

2015-06-09T21:19:52+00:00 June 9th, 2015|Autism, Autism, News, Patient Stories, Stem Cell Therapy|

Inside High School Football Report on Hall of Fame Coach and Stem Cell Recipient, Sam Harrell

Sam, who suffers from multiple sclerosis, was forced to retire as Ennis (Texas) High School’s head football coach due to his debilitating symptoms. Sam’s first two treatments using stem cells harvested from his own fat did not yield long lasting, positive results. However, after his third and fourth trips to the Stem Cell Institute in Panama for umbilical cord tissue-derived mesenchymal stem cells, Sam’s life turned around. Now, Sam is back in the game again!

Clinical Trials for Multiple Sclerosis and Rheumatoid Arthritis using Umbilical Cord Tissue Mesenchymal Stem Cells

Stem Cell Institute and Medistem Panama founder, Neil Riordan, PhD discusses clinical trials for multiple sclerosis and rheumatoid arthritis using umbilical cord tissue-derived mesenchymal stem cells at our fall stem cell seminar in San Antonio.

For more information about these trials and others, please visit www.translationalbiosciences.com. The multiple sclerosis trial is full but the RA trial is still recruiting as of November 24, 2014.

Highlights include:

How do we select umbilical cords for use? Medistem has identified proteins and genes in the cells that allow us to screen hundreds of umbilical cords to select only the ones containing the specific types of cells that have the best anti-inflammatory properties, the best immune modulating capacity and the best ability to stimulate regeneration.

How therapy using umbilical cord tissue-derived mesenchymal stem cells (MSCs) differs from bone marrow transplants used in cancer patients.

Properties of umbilical cord MSCs:

  • Modulate the immune system
  • Increase the number of T-regulatory cells
  • Block clonal expansion of activated T cells
  • MSCs in patients with autoimmune diseases don’t work properly

How demyelination occurs in MS patients and how MSCs act on the immune system to slow it down or stop it.

Treated MS patient follow-up survey results at 120 days and 1 year after treatment.

Television news story about Sam Harrell’s return to coaching football after severe MS symptoms forced him into early retirement.

Results from a 172 patient study on treating rheumatoid arthritis with intravenous umbilical cord tissue mesenchymal stem cells in which all patients improved.

Trial Information

These trials may be viewed on the National Institutes of Health web site www.clinicaltrials.gov

Umbilical Cord Tissue-derived Mesenchymal Stem Cells for Rheumatoid Arthritis

Feasibility Study of Human Umbilical Cord Tissue-Derived Mesenchymal Stem Cells in Patients With Multiple Sclerosis

Those interested in stem cell therapy for MS may still apply for private treatment on this site.

Stem Cell Therapy for Multiple Sclerosis: Ron McGill

Ron McGill suffers from relapsing-remitting multiple sclerosis. He was started experiencing symptoms in 2009 but was not diagnosed with MS until January of 2013. He received several infusion and injections of human umbilical cord-tissue derived stem cells at the Stem Cell Institute in late October and Early November 2013.

In this video, Ron shares his story of discovery and recovery at a Stem Cell Institute seminar in San Antonio in October 2014.

For more information on MS therapy at the Stem Cell Institute in Panama, please visit: https://www.cellmedicine.com/stem-cell-therapy-for-multiple-sclerosis-3/

Good afternoon.

I was diagnosed with relapsing-remitting MS in January of 2013. My symptoms started with tingling and numbness in my hands and feet migraine headaches in April, 2009. Visits to the doctors concluded that job stress-related migraines were all it was.

My high tolerance for pain accepted the results and I went on with life. This was an extremely poor decision on my part. My symptoms remained constant but non-progressing until November of 2011. In attempting to kick a soccer ball, I lost my balance and I fell. I wrote it off as being out of shape and clumsy. A fall on a treadmill and down a stairwell in early 2012 was my final wakeup call. It solidified that there was more wrong with me than normal.

My quest to find out what was causing my issues and how to resolve them was started.

Starting from behind and (inaudible) to catch up, I did several things. I made immediate dietary changes. Sodas, fast food, canned food, alcohol – eliminated. Red meat, dairy, bread, pasta – reduced drastically. Chicken, fish, fresh fruits, vegetables – doubled. I went on a weight loss and body detox regimen. I replaced impact aerobic exercises I could no longer do with swimming.

I made the most of my insurance. I literally became a human pin cushion. Everybody was sticking me. I looked outside traditional medicine: acupuncturist, building my immune system and pure vitamin regimens. While I made great strides in changing my life, I was testing healthier, a progression of worse symptoms continued to happen. Severe leg and back aches, leg stingers, twitching, lost grip and more loss of balance.

It was determined that MS was my cause. My instability had me falling one to two times a month. I reached my lowest point waking up immobile from the waist down on a Wednesday morning in February of 2013.

With my motor skills seemingly erased from my memory, a deep cloud of panic overtook me. My confidence went out the window. I had to dig down extremely deep. I was able to regain mobility later that evening. I progressed to a penguin walk and very limited speed and distance over the next 6 months with the help of a walking stick and physical therapy.
Hours of online research for possible relief led to stem cell therapy.

After many months of research, doctor consultations, numerous conversations with people who had had stem cell therapy, heard about it, had relatives who had experienced it, I sent the email to the Stem Cell Institute.

After being accepted, I still had more conversations with Dr. Barnett and Cindy, asking more and more questions. They were extremely patient to everything I had.

The care provided for me upon my arrival and during my stay and departure in Panama was extremely good. The facility was simple, clean, efficient with a very helpful and friendly staff. The procedure was well-explained to me and carefully administered.

I was able to see results on my way back (on) November 3rd. I was able to walk farther and feel better. I was able to my walking stick in the back of my car for good two weeks later. Knock on wood, I haven’t fallen since October 23rd of 2013. My stamina, walking speed and stability have continued to increase. I do have momentary balance loss and heat can still wipe me out. My MS is still with me.

Do I feel (that) Panama was the right choice? For me, absolutely. I feel the infusion of healthy cells gave my body a huge boost to recover the majority of lost motor skills I had experienced. It also helped amplify the lifestyle changes I was already making to give me a faster and more positive result.

These successes have given me a more positive mental state that have allowed me to heal more and more.

What advice could I give you about stem cells? Research, research, research. There isn’t a price you can put on due diligence when it comes to your health. Make lifestyle changes at the cellular level in your body and amplify it with stem cell therapy.

In closing, I’d like to thank my wife for undying support and hours of research. I’d like to thank Dr. Riordan, (and) Stem Cell Institute for being at the cutting edge of healing diseases and I’d like to thank you all for allowing me to share with you today.

Neil Riordan, PhD Presents at American Academy of Anti-Aging Medicine’s 22nd Annual World Congress on Anti-Aging, Regenerative and Aesthetic Medicine in Orlando, May 15

Neil Riordan, PhD will Present “Umbilical Cord Mesenchymal Stem Cells in the Treatment of Autoimmune Diseases” at the 22nd Annual World Congress on Anti-Aging, Regenerative and Aesthetic Medicine at the Gaylord Palms Hotel in Orlando, Florida as part of the Specialty Workshop: “Stem Cells in Anti-Aging Medicine: An Update”.

Orlando, FL (PRWEB) May 13, 2014

Neil Riordan, PhD will Present “Umbilical Cord Mesenchymal Stem Cells (MSC) in the Treatment of Autoimmune Diseases” at the 22nd Annual World Congress on Anti-Aging, Regenerative and Aesthetic Medicine at the Gaylord Palms Hotel in Orlando, Florida as part of the Specialty Workshop: “Stem Cells in Anti-Aging Medicine: An Update”.

The primary focus of this workshop is to teach medical professionals how to successfully incorporate stem cell treatments into their practices. Expert faculty will cover stem cell theory and clinical trial research for all aspects of regenerative medicine as well as stem cell treatment marketing.

Dr. Riordan will discuss: Allogeneic mesenchymal stem cells’ mechanisms of immune modulating activities; the importance of MSC placement for clinical effect; human clinical trials demonstrating efficacy; alternative routes of MSC delivery; dose and frequency; and clinical safety of MSC.

The conference will be held from May 15 – 17, 2014 at the Gaylord Palms Hotel in Orlando, Florida. For more information, please visit http://www.a4m.com/anti-aging-conference-orlando-2014-may.html.

About Neil Riordan PhD
Dr. Riordan is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI’s stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).

Under the umbrella of MPI subsidiary Translational Biosciences, MPI and SCI are currently conducting five IRB-approved clinical trials in Panama for multiple sclerosis, rheumatoid arthritis and osteoarthritis using human umbilical cord-derived mesenchymal stem cells, mesenchymal trophic factors and stromal vascular fraction. Additional trials for spinal cord injury, autism and cerebral palsy are slated to commence in 2014 upon IRB approval.

Dr. Riordan is an accomplished inventor listed on more than 25 patent families, including 11 issued patents. He is credited with a number of novel discoveries in the field of cancer research since the mid-1990s when he collaborated with his father Dr. Hugh Riordan on the effects of high-dose intravenous vitamin C on cancer cells and the tumor microenvironment. This pioneering study on vitamin C’s preferential toxicity to cancer cells notably led to a 1997 patent grant for the treatment of cancer with vitamin C. In 2010, Dr. Riordan received another patent for a new cellular cancer vaccine.

Dr. Riordan is also the founder of Aidan Products, which provides health care professionals with quality nutraceuticals including Stem-Kine, the only nutritional supplement that is clinically proven to increase the amount of circulating stem cells in the body for an extended period of time. Stem-Kine is currently sold in 35 countries.

Dr. Riordan earned his Bachelor of Science at Wichita State University and graduated magna cum laude. He received his Master’s degree at the University of Nebraska Medical Center. Dr. Riordan completed his education by earning a Ph.D. in Health Sciences at Medical University of the Americas.

About Stem Cell Institute Panama
Founded in 2007 on the principles of providing unbiased, scientifically sound treatment options; the Stem Cell Institute (SCI) has matured into the world’s leading adult stem cell therapy and research center. In close collaboration with universities and physicians world-wide, our comprehensive stem cell treatment protocols employ well-targeted combinations of autologous bone marrow stem cells, autologous adipose stem cells, and donor human umbilical cord stem cells to treat: multiple sclerosis, spinal cord injury, osteoarthritis, rheumatoid arthritis, heart disease, and autoimmune diseases.

In partnership with Translational Biosciences, a subsidiary of Medistem Panama, SCI provides clinical services for ongoing clinical trials that are assessing safety and signs of efficacy for osteoarthritis, rheumatoid arthritis, and multiple sclerosis using allogeneic umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC), autologous stromal vascular fraction (SVF) and hU-MSC-derived mesenchymal trophic factors (MTF). In 2014, Translation Biosciences expects to expand its clinical trial portfolio to include spinal cord injury, heart disease, autism and cerebral palsy.

For more information on stem cell therapy:

Stem Cell Institute Website: http://www.cellmedicine.com

Stem Cell Institute
Via Israel & Calle 66
Plaza Pacific Office #2A
Panama City, Panama

About Medistem Panama Inc.

Since opening its doors in 2007, Medistem Panama Inc. has developed adult stem cell-based products from human umbilical cord tissue and blood, adipose (fat) tissue and bone marrow. Medistem operates an 8000 sq. ft. ISO 9001-certified laboratory in the prestigious City of Knowledge. The laboratory is fully licensed by the Panamanian Ministry of Health and features 3 class 10000 clean rooms, class 100 laminar flow hoods, and class 100 incubators.

Medistem Panama Inc.
Ciudad del Saber, Edif. 221 / Clayton
Panama, Rep. of Panama

Phone: +507 306-2601
Fax: +507 306-2601

Web site: http://www.medistempanama.com

About Translational Biosciences
A subsidiary of Medistem Panama Inc., Translational Biosciences was founded solely to conduct clinical trials using adult stem cells and adult stem cell-derived products.

Translational Biosciences Web Site: http://www.translationalbiosciences.com

Medistem Panama Awarded ISO 9001 International Global Certification

Medistem Panama ISO 9001-2008 Logo

Awarded this:

CERTIFICATION

for the Quality Management System of:

MEDISTEM PANAMA

Offices included in the scope:

Ciudad del Saber, Edificio # 221, piso # 2,
Clayton, Ancón
Panama City, Republic of Panama

IAF ENAC Logos

The scope includes the following activities:

  • Isolation of stem cells from adipose tissue(ADSC) and mononuclear cells from bone marrow.
  • Expansion and harvest of mesenchymal stem cells from umbilical cord, adipose tissue and its derivatives.

ISO 9001:2008

Valid from 19, June 2016
Granted from Panama 20, June 2013

Antonio Martin
Director

IGC10126

IGC10126

Stem cell treatment in Panama benefits autistic Glenburn youth

Autism Stem Cell Patient Ken Kelley

As Kenny Kelley of Glenburn awaits an infusion of adult stem cells at a Panamanian city in November 2011, a Panamanian physician holds two syringes containing the cells. Autistic since birth, Kenny has undergone several such infusions since 2009.

As Kenny Kelley of Glenburn awaits an infusion of adult stem cells at a Panamanian city in November 2011, a Panamanian physician holds two syringes containing the cells. Autistic since birth, Kenny has undergone several such infusions since 2009.[/caption]

By Dale McGarrigle, Of The Weekly Staff
Bangor Daily News
Posted Sept. 14, 2012, at 12:17 p.m.

GLENBURN — Now Kenny can read.

Kenny Kelley can now also do many things that other 11-year-olds take for granted. According to his mother, Marty Kelley, that’s because injections of adult stem cells, taken from umbilical cord blood, have helped Kenny to shake off the shackles of autism, with which he was first diagnosed at age 2.

“The results from stem cells can be seen everyday in his amazing thoughts and vast imagination!!,” Marty Kelley wrote in her blog, http://www.kensjourneytorecovery.blogspot.com/. “How lucky we are for such a miracle treatment!”

Autism is a brain disorder found in children that interferes with their ability to communicate and relate to other people. Autism affects 1 in 88 children and 1 in 54 boys. What causes autism has not been established.

Stem cells are the body’s internal repair system and can fix and replace damaged tissue. These unspecialized cells are a blank slate, capable of transforming into muscle cells, blood cells, and brain cells. Stem cells can also renew themselves by dividing and giving rise to more stem cells.

Stem cells taken from umbilical cord blood, such as Kenny received, are the least likely to be rejected.

The stem-cell treatment is the latest effort by Marty and her husband, Donald, to find ways to improve Kenny’s life. The Kelleys also have two other children: Philip, 13, and Caroline-Grace, 6.

First was in-home treatment in a mild hyperbaric oxygen chamber, three hours a day equaling 800 hours over the course of two years, beginning when Kenny was 5 ½ to 6 years old. This was coupled with a Specific Carbohydrate Diet, which restricts the use of complex carbohydrates and eliminates refined sugar and all grains and starch from the diet.

“We saw results right away with the chamber,” Marty recalled in a recent interview. “He made slow gains, such as tracing the alphabet.”

Then the Kelleys discovered on the Internet the story of Matthew Faiella, a New York boy who has been making great strides after stem-cell treatment in Panama for his autism. They decided to follow suit.

Why take this path, when there has been little scientific research into the use of stem cells to treat autism?

“We were willing to do it as long as it’s safe, and I’ve researched this,” Marty said. “Stem cells are very natural. I’m not a scientist, but I care much more than any scientist would, and I would never do anything to hurt my baby.”

When Kenny went for his first stem-cell treatment in July 2009, at the Stem Cell Institute in Costa Rica, Marty assessed the condition of her then 8-year-old son in her blog http://www.kensjourneytorecovery.blogspot.com:

• Behavior: Screaming, aggressive, giggles/silly/inappropriate with his brother or new people, running around, destructive, uncooperative while being dressed, hitting, not potty trained (still wearing diapers).

• Speech: Vocabulary of a 4-year-old. He can talk, but it is difficult for strangers to understand him. Answers some questions, but he does not understand or like why, when, or how questions.

• Physical: A body the size of a 5-year-old boy.

Kenny has had stem-cell treatments in 2009, 2010, and May and November of 2011. The repeated treatments are required because adult stems cells will work repairing cells for a period of time, about six months, then leave the body.

“When I think I’ve seen his skills level out, we’ll go for another treatment,” explained Marty.

What are some of the changes that Kenny has undergone in the past three years? First came the ability to read and clearer speech.

“When he got back, he just picked up a book and started reading, and I could understand every word,” said Mike Hughes, Marty’s brother. “It was like a light just turned on.”

Other gains: Kenny is talking about past events for the first time, and he’s conversational now. He expresses opinions and looking ahead to the future. He was finally potty trained at age 9. He’s doing math now. He’s calmed down considerably. This summer, he went to summer camp, staying overnight for three nights, in the same cabin as Philip.

“There’s no doubt in my mind how much he’s progressing,” Marty said. “We’re working on catching up right now, and how do we best do that?”

The costly treatment, which isn’t covered by insurance, hasn’t been approved yet by the Food and Drug Administration. Despite the fact that the stem cells come from the human body, the cells are considered a new drug by the FDA and are subject to stringent research and testing that can take years.

So this leaves the Kelleys and others like them seeking stem-cell treatment, going overseas to get it.

“It’s just a matter of how much are you going to spend,” Marty said. “There’s no treatment here that was going to do this much for him.”

2012-09-14T17:33:47+00:00 September 14th, 2012|Autism, News, Stem Cell Therapy|

Immune Cells Killing Stem Cells and Stem Cells Killing Immune Cells

Knight et al. J Neurol Sci.
Several studies have demonstrated that stem cells are useful in the treatment of multiple sclerosis. The Cellmedicine clinic published previously in collaboration with the University of California San Diego that 3 patients treated with their own fat derived stem cells entered remission. Other studies are ongoing, including a study at the Cleveland Clinic in which bone marrow stem cells differentiated into mesenchymal stem cells are being administered into patients with multiple sclerosis. Unfortunately the mechanisms by which therapeutic effects occur are still largely unknown. One general school of thought believes that stem cells are capable of differentiating into damaged brain cells. The other school of thought believes that stem cells are capable of producing numerous growth factors, called trophic factors, that mediate therapeutic activity of the stem cells. Yet another school of thought propagates the notion that stem cells are merely immune modulatory cells. Before continuing, it is important to point out that stem cell therapy for multiple sclerosis involving autologous hematopoietic transplants is different than what we are discussing here. Autologous (your own) hematopoietic stem cell therapy is not based on regenerating new tissues, but to achieve the objective of extracting cells from a patients, purifying blood making (hematopoietic) stem cells, destroying the immune system of the recipient so as to wipe out the multiple sclerosis causing T cells, and subsequently readministering the patient’s own cells in order to regenerate the immune system. This approach, which was made popular by Dr. Richard Burt from Northwestern University.
In order to assess mechanisms of how stem cells work in multiple sclerosis it is necessary to induce the disease in animals. The most widely used animal model of multiple sclerosis is the experimental allergic encephalomyelitis model. This disease is induced in female mice that are genetically bred to have a predisposition to autoimmunity. These animals are immunized with myelin basic protein or myelin oligodendrocyte protein. Both of these proteins are components of the myelin sheath that protects the axons. In multiple sclerosis immune attack occurs against components of the myelin sheath. Therefore immunizing predisposed animals to components of the myelin sheath induces a disease similar to multiple sclerosis. The EAE model has been critical in development of some of the currently used treatments for multiple sclerosis such as copaxone and interferon.
Original studies have demonstrated that administration of bone marrow derived mesenchymal stem cells protects mice from development of EAE. This protection was associated with regeneration on oligodendrocytes as well as shifts in immune response. Unfortunately these studies did not decipher whether the protective effects of the stem cells were mediated by immune modulation, regeneration, or a combination of both. Other studies have shown that MSC derived from adipose tissue had a similar effect. One interesting point of these studies was that the stem cell source used was of human origin and the recipient mice were immune competent. One would imagine that administration of human cells into a mouse would result in rapid rejection. This did not appear to be the case since the human cells were found to persist and also to differentiated into human neural tissues in the mouse. One mechanism for this “immune privilege” of MSC is believed to be their low expression of immune stimulatory molecules such as HLA antigens, costimulatory molecules (CD80/86) and cytokines capable of stimulating inflammatory responses such as IL-12. Besides not being seen by the immune system, it appears that MSC are involved in actively suppressing the immune system. In one study MSC were demonstrated to naturally home into lymph nodes subsequent to intravenous administration and “reprogram” T cells so as to suppress delayed type hypersensitive reactions. In those experiments scientists found that the mechanism of MSC-mediated immune inhibition was via secretion of nitric oxide. Other molecules that MSC use to suppress the immune system include soluble HLA-G, Leukemia Inhibitor Factor (LIF), IL-10, interleukin-1 receptor antagonist, and TGF-beta. MSC also indirectly suppress the immune system by secreting VEGF which blocks dendritic cell maturation and thus prevents activation of mature T cells.
While a lot of work has been performed investigating how MSC suppress the immune system, relatively little is known regarding if other types of stem cells, or immature cells, inhibit the immune system. This is very relevant because there are companies such as Stem Cells Inc that are using fetally-derived progenitor cells therapeutically in a universal donor fashion. There was a paper from an Israeli group demonstrating that neural progenitors administered into the EAE model have a therapeutic effect that is mediated through immune modulation, however, relatively little work has been performed identifying the cell-to-cell interactions that are associated with such immune modulation.
Recently a paper by Knight et al. Cross-talk between CD4(+) T-cells and neural stem/progenitor cells. Knight et al. J Neurol Sci. 2011 Apr 12 attempted to investigate the interaction between immune cells and neural stem cells and vice versa. The investigators developed an in vitro system in which neural stem cells were incubated with CD 4 cells of the Th1 (stimulators of cell mediated immunity), Th2 (stimulators of antibody mediated immunity) and Th17 (stimulators of inflammatory responses) subsets. In order to elucidate the impact of the death receptor (Fas) and its ligand (FasL), the mouse strains lpr and gld, respectively, were used.
The investigators showed that Th1 type CD4 cells were capable of directly killing neural stem cells in vitro. Killing appeared to be independent of Fas activation on the stem cells since gld derived T cells or lpr derived neural stem cells still participated in killing. Interestingly, neural stem cells were capable of stimulating cell death in Th1 and Th17 cells but not in the Th2 cells. Killing was contact dependent and appeared to be mediated by FasL expressed on the neural stem cells. This is interesting because some other studies have demonstrated that FasL found on hematopoietic stem cells appears to kill activated T cells. In the context of hematopoietic stem cells this phenomena may be used to explain clinical findings that transplanting high numbers of CD34 cells results in a higher engraftment, mediated in part by killing of recipient origin T cells.
The finding that neural stem cells express FasL and selectively kill inflammatory cells (Th1 and Th17) while sparing anti-inflammatory cells (Th2) indicates that the stem cells themselves may be therapeutic by exerting an immune modulatory effect. One thing that the study did not do is to see if differentiated neural stem cells would mediate the same effect. In other words, it is essentially to know if the general state of cell immaturity is associated with inhibition of inflammatory responses, or whether this is an activity specific to neurons. As mentioned above, previous studies have demonstrated that mesenchymal stem cells (MSC) are capable of eliciting immune modulation through a similar means. Specifically, MSC have been demonstrated to stimulate selective generation of T regulatory cells. This cell type was not evaluated in the current study, however some activities of Th2 cells are shared with Treg cells in that both are capable of suppressing T cytotoxic cell activation. In the context of explaining biological activities of stem cell therapy studies such as this one stimulate the believe that stem cells do not necessarily mediate their effects by replacing damaged cells, but by acting on the immune system. Theoretically, one of the reasons why immature cells are immune modulatory in the anti-inflammatory sense may be because inflammation is associated with oxidative stress. Oxidative stress is associated with mutations. Conceptually, the body would want to preferentially protect the genome of immature cells given that the more immature the cells are, the more potential they have for stimulation of cancer. Mature cells have a limited self renewal ability, whereas immature cells, given they have a higher potential for replication are more likely to accumulate genomic damage and neoplastically transform.