Stem Cell Institute Public Seminar on Adult Stem Cell Therapy Clinical Trials in New York City May 17th, 2014

New York, NY (PRWEB) April 09, 2014

The Stem Cell Institute, located in Panama City, Panama, will present an informational umbilical cord stem cell therapy seminar on Saturday, May 17, 2014 in New York City at the New York Hilton Midtown from 1:00 pm to 4:00 pm.

Speakers include:

Neil Riordan PhD“Clinical Trials: Umbilical Cord Mesenchymal Stem Cell Therapy for Autism and Spinal Cord Injury”

Dr. Riordan is the founder of the Stem Cell Institute and Medistem Panama Inc.

Jorge Paz-Rodriguez MD“Stem Cell Therapy for Autoimmune Disease: MS, Rheumatoid Arthritis and Lupus”

Dr. Paz is the Medical Director at the Stem Cell Institute. He practiced internal medicine in the United States for over a decade before joining the Stem Cell Institute in Panama.

Light snacks will be served afterwards. Our speakers and stem cell therapy patients will also be on hand to share their personal experiences and answer questions.

Admission is free but space in limited and registration is required. For venue information and to register and reserve your tickets today, please visit: http://www.eventbrite.com/e/stem-cell-institute-seminar-tickets-11115112601 or call Cindy Cunningham, Patient Events Coordinator, at 1 (800) 980-7836.

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.

To-date, SCI has treated over 2000 patients.

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

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 webSite: http://www.translationalbiosciences.com

Email: trials(at)translationalbiosciences(dot)com

Sam Harrell’s Stem Cell Journey: Stem Cell Therapy for Multiple Sclerosis

Sam Harrell sent us this homemade video documenting his progress from 2010 until now (2014). Sam was coaching football at Ennis high school in Texas when MS struck him hard, forcing him to retire. Since then, after several rounds of stem cell therapy at the Stem Cell Institute in Panama, Sam has returned to coaching football, something he though that he would never be able to do again.

For more information about umbilical cord tissue-derived mesenchymal stem cell therapy for MS, please visit: http://www.cellmedicine.com/stem-cell-therapy-for-multiple-sclerosis-3/

Umbilical Cord Stem Cell Therapy Clinical Trial for Multiple Sclerosis Gets Green Light

Translational Biosciences Site Header

Dallas, TX (PRWEB) April 03, 2014

Translational Biosciences, a subsidiary of Medistem Panama, has received the green light for a phase I/II clinical trial using human umbilical cord-derived mesenchymal stem cells (UC-MSC) for multiple sclerosis from the Comité Nacional de Bioética de la Investigación (CNEI) Institutional Review Board (IRB) in Panama.

According to the US National Multiple Sclerosis Society, in Multiple Sclerosis (MS), an abnormal immune-mediated T cell response attacks the myelin coating around nerve fibers in the central nervous system, as well as the nerve fibers themselves. This causes nerve impulses to slow or even halt, thus producing symptoms of MS that include fatigue; bladder and bowel problems; vision problems; and difficulty walking. The Cleveland Clinic reports that MS affects more than 350,000 people in the United States and 2.5 million worldwide.

Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve MS symptoms. Because these cells are immune privileged, the recipient’s immune system does not reject them. These properties make UC-MSC interesting candidates for the treatment of multiple sclerosis and other autoimmune disorders.

Each patient will receive seven intravenous injections of UC-MSC over the course of 10 days. They will be assessed at 3 months and 12 months primarily for safety and secondarily for indications of efficacy.

The stem cell technology being utilized in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panama’s 8000 sq. ft. ISO-9001 certified laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.

From his research laboratory in Dallas, Texas, Dr. Riordan commented, “Umbilical cord tissue provides an abundant, non-controversial supply of immune modulating mesenchymal stem cells. Preclinical and clinical research has demonstrated the anti-inflammatory and immune modulating effects of these cells. We look forward to the safety and efficacy data that will be generated by this clinical trial; the first in the western hemisphere testing the effects of umbilical cord mesenchymal stem cells on patients with multiple sclerosis.”

The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute.

For detailed information about this clinical trial visit http://www.clinicaltrials.gov . If you are a multiple sclerosis patient between the ages of 18 and 55, you may qualify for this trial. Please email trials (at) translationalbiosciences (dot) com for more information about how to apply.

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
Email: trials@translationalbiosciences.com

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

About Stem Cell Institute Panama

Founded in 2007 on the principles of providing unbiased, scientifically sound treatment options; the Stem Cell Institute 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. To-date, the Institute has treated over 2000 patients.

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

Neil Riordan PhD on Peri-lymphatic Stem Cell Treatment for Multiple Sclerosis

Stem Cell Pioneers featured Dr. Riordan in its February installment of “Ask the Doctor”, a monthly segment that features stem cell scientists and doctors answering questions from readers about stem cell therapy.

Over the next several days, we will share these questions and Dr. Riordan’s answers with our readers.

Question: I have heard from patients that you are doing intralymphatic stem cell injections. I think there are a lot of IntraLymph studies on other things like allergies, but none on stem cells that I can find. What is the reasoning behind this new route of administration? If stem cells get stuck in the lungs and we worry about that, why inject them directly into the lymph system where they would go to the spleen?

Dr. Riordan’s Answer: The goal of our treatments umbilical cord mesenchymal stem cells for patients with multiple sclerosis really has nothing to do with repairing the damaged or destroyed myelin in the lesions found in the brain and spinal cord. Because multiple sclerosis is first and foremost an autoimmune disease our goal is to address the immune dysfunction. At the root of the disease is a pool of immune cells called T-cells, which actively proliferate, cross the blood brain barrier, and attack myelin. Our primary goal then is to interfere with myelin-specific T-cell reproduction (something called “clonal expansion’). Mesenchymal stem cells (MSCs) have been shown in multiple studies to have the capacity to block this so-called clonal expansion of activated T cells. In a way MSCs immunosuppress, but unlike some drugs that suppress the immune system this specific blocking of activated T cells does not quash the entire immune system—the cells and their secretions only block the clonal expansion. Other drugs that suppress the immune system—for example hydrocortisone—have an effect on the entire immune system, which can increase the risk of the recipient to infectious diseases and even some cancers.

If it were the goal of the treatment to induce remyelination then certainly the route of delivery would be of greatest importance. You would want for the cells (or whatever proposed remyelination agent) to be as close to the lesions requiring the repair as possible. So I understand the rationale for the question.

In my opinion it will be difficult to successfully treat multiple sclerosis by remyelination alone because if you do not address the immune problem you will continue to lose myelin. Therefore, getting the cells to the lesions for myelin repair is not particularly important. Further support for this opinion is that there is very good evidence that the body has the innate ability to regenerate myelin without intervention. There are two good examples of this. The first example comes from a condition called Guillain–Barré syndrome. The syndrome is an autoimmune disease that results from an immune attack on the myelin of peripheral nerves. There is an ascending paralysis and the condition can be life threatening if the paralysis gets high enough to affect breathing. It is treatable and generally temporary. In 80% of the patients the underlying nerves are not irreparably damaged and there will be no long-term neurologic symptoms. 20% experience permanent nerve damage because the axons of the nerves are damaged. The good news is that the disease is temporary. The better news is that in the mild cases in which the axons were not destroyed, complete remyelination occurs—the body has the capacity to restore myelin.

The second example comes from a phenomenon seen with serial MRI images of the brains in people with MS. Fifty percent of these low intensity lesions known as “black holes” revert within one month of appearance, indicating that remyelination has occurred spontaneously.

Further support for the “treat the immune system and not the Central Nervous System” in MS comes from the work of several groups, including Northwestern University who are using chemotherapeutic “conditioning”, ie. wiping out the immune system (and the by-standing hematopoietic stem cells) followed by bone marrow reconstitution using previously harvested bone marrow stem cells. There are published results of many cases improving without anything having been done to address the myelin loss.
To the question of intra-lymphatic injections: There has been no work on “intra-lymphatic” injections. We are looking into peri-lymphatic (near the lymph nodes) injections of huMSCs for patients who are refractory to intravenous treatment.
Here is a little background on this subject: Dr. Arnold Caplan of Case Western Reserve, the scientist to first describe mesenchymal stem cells, was in Panama last year consulting with us. He also presented at a conference that we cosponsored. In one of my discussions with Dr. Caplan he casually mentioned that whenever they injected mesenchymal stem cells into the abdominal cavity of animals that did not have an active inflammatory process in there in the cavity the MSC’s would automatically go to the abdominal lymph chains. They were able to determine this because they use cells that were labeled with the florescent probe. I found this very interesting given that the 70-80% of the immune cells of your body reside in the abdominal cavity in and around the intestines.

The rationale for peri-lymphatic treatment is relatively simple. Firstly, the goal of therapy in autoimmune disease is to induce immune tolerance in the face of immune intolerance. The majority of the immune cells are found in the lymphatic (which includes the lamina propria) system of the gut. MCSs will, when lacking a more compelling inflammatory signal, migrate to the lymph nodes. Once in the lymph nodes they will migrate and interact with the immune cells (T-cells and T-cell priming dendritic cells). We know for a fact that MSCs interfere with dendritic cell priming of T-cells.

My book will be coming out in April. It will go into greater detail on this subject and many more. There are case histories as well as treatment protocols and rationale for each condition. Information about how to get the book “Mesenchymal Stem Cells: Nature’s Pharmacy” will be on www.Riordanbooks.com, as well as on www.amazon.com.

Multiple sclerosis patient retires his walking stick after umbilical cord-derived stem cell therapy

From: mcgillron
Date: Wed, Nov 27, 2013 at 11:51 AM
Subject: Happy Thanksgiving!
To: edited_for_privacy@cellmedicine.com

Dr Barnett / Dr Hernandez & all staff at Clinic,

It’s a very special Thanksgiving for my household & I owe it to the efforts of all of you!

I’ve been walking without my stick since returning from stem cell therapy. 1 week of holding it for security & going on 3rd week of it riding in truck of my car. My stability is becoming more consistent & controlled. I am walking farther longer, riding bicycle more rhythmic & swimming smoother strokes.

Results are much greater than I expected. I believe the lifestyle changes, vitamin regimen, herbals, exercise & positive attitude adopted 14 months prior to visiting you allowed me to receive maximum benefit from the stem cell therapy.

I look forward to progressing my abilities back to a higher level over the next months.

If you would like me to share what I’ve done & am doing to get my results, feel free to give my email.

Dr Hernandez – please stay in contact on the herbal adjustments I’m making to solve final 2 deficiencies.

THANKS AGAIN for your hospitality & care!

Ron Mc Gill

Stem Cell Therapy for Relapsing-Remitting MS

Bonnie, who suffers from relapsing-remitting multiple sclerosis (MS) received a combination of human umbilical cord mesenchymal stem cells and adipose-derived cells administered daily over the course of 5 days.

Just wanted to send an update as I am really excited! I received my very first stem cells on 10/22/13, it has been less then a month and I am happy to report that I have tons more energy by balance is improving every day, I have no more foot drop and not even a healing I was looking for but I put my glasses on the other day only to find they made my vision blurry I didn’t need them, I am already saving for my next treatment! I can’t thank you all enough as I feel like I have a future with my 5 small children now, if you ever need someone to talk to future patients I would be happy to scream my praises! Looking forward to more and more improvement!

Sincerely,
Bonnie Barrington

For more information about MS clinical investigations at the Stem Cell Insitute: Stem Cell Therapy for Multiple Sclerosis

Sam Harrell demonstrates his progress after receiving umbilical cord stem cells + fat stem cells for multiple sclerosis

Texas high school Hall of Fame football coach Sam Harrell talks about his progress after undergoing several stem cell treatments for secondary progressive multiple sclerosis at the Stem Cell Institute in Panama City, Panama.

Sam is speaking from the clinic in Panama while undergoing his fourth 5-day course of combination human umbilical cord-derived mesenchymal stem cells and fat-derived stromal vascular fraction cells.

“I came by myself this time and that’s just a sign of how much better I’ve gotten. …the last times I’ve come I had to get in a wheel chair [off the plane] and I just walked through the airport this time. People ask me. ‘Do you think it really helps?’. Well, just look! I am walking through the airport with no aids.” [Sam demonstrates how he used to walk before treatment] “I took little steps. If I needed to turn around, I had to do like this.” [Sam demonstrates a slow, shuffling turn] “I don’t have a rope but now I can jump rope.” [sam demonstates jumping rope and walks quickly around the room demonstrating quick changes in directions] “Before, I couldn’t jump rope. I couldn’t do any of that. Now I can do those things. I used to have to think about my steps. I’d have to think about right leg, and left leg and now I don’t have to think. I catch myself doing that. I walk somewhere and I think, ‘hey I didn’t have to think about walking from there to there. I just got up and walked like I used to. Now I can make quick moves. I couldn’t do any of that before.”

“…I coached football and I had to retire. I never thought I’d coach football again. Just this last year, I coached football again. Amazing. I thought I would never do that again. I coached this past year and I plan on doing it again. I’m thank to the Stem Cell Institute in Panama and I am thankful to God above. He’s smiling on me too. It’s an amazing story, I think.”

Sam Harrell Texas High School Football Hall of Fame: http://www.brownwoodnews.com/index.php?option=com_content&view=article&id=10918:harrell-to-be-inducted-into-the-texas-high-school-football-hall-of-fame&catid=39:sports&Itemid=62

Links:

Stem Cell Therapy for MS

More Patient Stories

Blood from young mice helps older mice with multiple sclerosis

A new mouse study has shown that blood from young mice helps old mice to heal damage caused by MS.

MS causes myelin, which insulates nerve cells electrically, to become damaged. Stem cells can produce myelin but they lose efficiency in older patients.

Researchers in the UK have found a way to reverse this age-related efficiency loss. By linking the bloodstreams of young mice to old mice with myelin damage, the older stem cells were reactivated and boosted myelin production.

White blood cells from the young mice called macrophages were found at myelin damage sites in the old mice. These cells engulf and destroy pathogens and debris, including destroyed myelin.

Amy Wagers, from Harvard University says, “We know this debris inhibits regeneration, so clearing it up is important.”

2012-01-16T18:58:20+00:00January 16th, 2012|Multiple Sclerosis, News, Stem Cell Research|

Stem Cells May Reverse Age-Related Multiple Sclerosis Effects

Proof-of-principle study provides hope for stimulating remyelination

Scientists at Joslin Diabetes Center, Harvard University, and the University of Cambridge have found that the age-related impairment of the body’s ability to replace protective myelin sheaths, which normally surround nerve fibers and allow them to send signals properly, may be reversible, offering new hope that therapeutic strategies aimed at restoring efficient regeneration can be effective in the central nervous system throughout life.

In a proof-of-principle study published in the journal Cell Stem Cell, the researchers report that defects in the regeneration of the myelin sheaths surrounding nerves, which are lost in diseases such as multiple sclerosis may be at least partially corrected following exposure of an old animal to the circulatory system of a young animal. Myelin is a fatty substance that protects nerves and aids in the quick transmission of signals between nerve cells.

Using a surgical technique, the researchers introduced an experimental demyelinating injury in the spinal cord of an old mouse, creating small areas of myelin loss, and then exposed those areas to cells found the blood of a young mouse. By doing so, they found that the influx of certain immune cells, called macrophages, from the young mouse helped resident stem cells restore effective remyelination in the old mouse’s spinal cord. This “rejuvenating” effect of young immune cells was mediated in part by the greater efficiency of the young cells in clearing away myelin debris created by the demyelinating injury. Prior studies have shown that this debris impedes the regeneration of myelin.

“Aging impairs regenerative potential in the central nervous system,” says author Amy J. Wagers, PhD, an associate professor of stem cell and regenerative biology at Harvard University and Joslin, who co-led the study with Professor Robin Franklin, director of the MS Society’s Cambridge Centre for Myelin Repair at the University of Cambridge. “This impairment can be reversed, however, suggesting that the eventual development of cell-based or drug-based interventions that mimic the rejuvenation signals found in our study could be used therapeutically.”

This could be particularly useful, she adds, in treating MS, which typically spans many decades of life, and thus is likely to be influenced by age-dependent reductions in the ability of myelin to regenerate. In MS, the body’s own immune system attacks the myelin sheath and prevents nerve fibers in the brain from sending signals properly, which can cause mild symptoms such as limb numbness or more serious ones like losing the ability to walk or speak. As people with MS age, remyelination decreases significantly, eventually causing permanent loss of nerve fibers.

“For MS sufferers,” says Franklin, “this means that, in theory, regenerative therapies will work throughout the duration of the disease. Specifically, it means that remyelination therapies do not need to be based on stem cell transplantation since the stem cells already present in the brain and spinal cord can be made to regenerate myelin, regardless of a person’s age.”

Other Joslin co-authors of the study were Tata Nageswara Rao and Jennifer L. Shadrach.

About Joslin Diabetes Center
Joslin Diabetes Center, located in Boston, Massachusetts, is the world’s preeminent diabetes research and clinical care organization. Joslin is dedicated to ensuring that people with diabetes live long, healthy lives and offers real hope and progress toward diabetes prevention and a cure. Joslin is an independent, nonprofit institution affiliated with Harvard Medical School.

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.