Neil Riordan PhD on stem cell expansion in stem cell therapy

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: Are there some conditions such as neurological ones that respond better when the cells are greatly expanded? Is a high quantity essential for success or is that something that may be more of a selling point at some clinics? I have also seen this advertised for COPD and other conditions. It’s almost like the more cells the better, but I would like your opinion.

Dr. Riordan’s Answer: That really depends on the quality of the cells after expansion. If they are still robust, not senescent, and still have a good secretion profile, then the more the better may be useful up to a point. If you take a small pool of starter cells and expand them to exhaustion, then I don’t think you are going to have a very good product. The MSCs used in Panama are not expanded beyond passage 5—a point at which there is no senescence in the population and they have a robust cytokine secretion profile. In order to use only cells that meet our release criteria, cells from approximately one (1.2 to be exact) out of 10 donated umbilical cords are used.

Contrast that to cells from a patient’s own fat tissue that are expanded. Firstly, the starting cells may, and many times are not very robust—they secrete little or no beneficial cytokines or chemokines, and must be expanded to hilt in order to hit the cell number. Please see my answer to number 7 for more on this subject.

This brings up a slightly different, yet related topic. There has been a lot of talk at recent meetings about more defined endpoints for the cells being used, and I couldn’t agree more. There are MSCs from bone marrow, menstrual blood, fat tissue, umbilical cord (even different parts of the umbilical cord—around the blood vessels, from the Wharton’s jelly, from the subepithelium, from the cord blood itself—which are most likely contaminants from a bruised placenta rather than the blood), teeth, amniotic membrane, amniotic fluid just to name sources in the “we didn’t mess with mother nature” adult stem cell world. Add to that the infinite variables when you consider the age and physical condition of the donor, particularly when using adipose or bone marrow as a source material and we, as a field, could be saying almost anything by using the term, “mesenchymal stem cell.” I think it is time that there is standardization in the field beyond the current definition of expressing/not expressing certain surface markers and the ability to differentiate into fat, bone, and cartilage. That standardization could come from using endpoints such as “remaining proliferative capacity (the number of doublings achievable in culture from the treatment cell bank), the secretome, even if there is standardization of one or two molecules, such as HGF, or one of the prostaglandins.

In the future I believe the field will take it a step further by measuring, even by a surrogate marker, the potential effects of the cells on the target condition. In the case of autoimmunity the cells and their secretions could be tested for their capacity to modulate the immune system. In the case of inflammatory conditions, the cells and their secretions could be tested for the ability to control or block inflammation.

Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients.

Zhang Z, Fu J, Xu X, Wang S, Xu R, Zhao M, Nie W, Wang X, Zhang J, Li T, Su L, Wang FS.
Research Center for Biological Therapy.

Link to Abstract on National Institutes of Health Website

Abstract

OBJECTIVE:
HAART largely decreases morbidity and mortality in chronic HIV-1-infected patients, but immune nonresponders (INRs) with full viral suppression still fail to reverse the immune deficiency. This study evaluated the safety and immunological responses of human umbilical cord mesenchymal stem cell (MSC) therapy in HIV-1-infected INRs.

DESIGN AND METHODS:
A total of 13 HIV-1-infected INRs were enrolled in this pilot prospectively open-labeled controlled clinical trial. Seven patients were administered three umbilical cord-MSC transfusions at 1-month interval during 12-months of follow-up, whereas six control patients were treated with saline in parallel. Immunological parameters were monitored in these patients throughout the trial.

RESULTS:
All patients tolerated the umbilical cord-MSC transfusions well throughout the trial. The umbilical cord-MSC transfusions preferentially increased circulating naive and central memory CD4 T-cell counts and restored HIV-1-specific IFN-γ and IL-2 production in the INRs. These enhancements in immune reconstitution were also associated with the reduction of systemic immune activation and inflammation in vivo.

CONCLUSIONS:
umbilical cord-MSC transfusions are well tolerated and can efficiently improve host immune reconstitution in INRs, suggesting that such treatments may be used as a novel immunotherapeutic approach to reversing immune deficiency in HIV-1-infected INRs (ClinicalTrials.gov identifier: NCT01213186).

Umbilical Cord Stem Cells: Regeneration, Repair, Inflammation and Autoimmunity – Neil Riordan PhD (Part 2 of 2)

In part 2, Dr. Riordan discusses how mesenchymal stem cells can affect tissue repair in spinal cord injury and in heart failure; benefit to heart is not the actual MSCs modeling new tissue. It is due to the trophic effects of MSC secretions; In rats, severed spinal cords re-grew after MSCs were implanted but the human MSCs did not form new cord tissue. The trophic factors secreted by the MSCs enable the spinal cord to repair itself.; Trophic factors from MSCs modulate the immune system by blocking clonal expansion of cytotoxic T-cells; There are 35 ongoing clinical trials using mesenchymal stem cells for autoimmune diseases; Safety of donor MSCs; Every mother has MSCs from each baby she has carried; Mothers have a lower incidence of autoimmune disease; Lifespan of mothers increased linearly with each child up to 14; There are 85 ongoing clinical trials using donor MSCs. Allogeneic MSCs from bone marrow have been approved in Canada and New Zealand to treat graft vs. host disease; limbal cells used in corneal transplants are MSCs; MSCs are useful in preventing donated organ rejection; glioma growth was found to be inhibited by MSCs; MSCs eliminated breast cancer in rats.

VIDEO – The Science of Mesenchymal Stem Cells and Regenerative Medicine – Arnold Caplan PhD (Part 4)

In part 4, Prof. Caplan talks about isolating mesenchymal stem cells from bone marrow using specialized; calf serum choosing different assays to prove multipotency – osteogenesis, chondrogenesis, adipogenesis; point of care with autologous bone marrow in orthopedic surgery; tissue engineering bone with lineage restricted MSCs; banking bone discarded bone marrow from orthopedic surgeries for future use;

Mesenchymal Stem Cells in Regenerative Medicine:Mechanisms of action, sources, and delivery options

Neil Riordan, PhD, Founder of the Stem Cell Institute in Panama City, Panama will be speaking today, Wednesday, Feb 6 at the STEMSO International Stem Cell Society 2013 Conference in Fort Lauderdale, FL.

The topic of Dr. Riordan’s discussion will be “Mesenchymal Stem Cells in Regenerative Medicine:Mechanisms of action, sources, and delivery options”

The theme for this year’s event is “Autologous Stem Cells: Who gets to decide…”

Stem cell treatments for chronic fatigue syndrome: Susan Lucey

“First I must say I have been steadily getting better. Everyone notices it. My long distance friends have all commented on the vitality and clarity in my voice. So much is changing in my body for the better. I can’t thank the staff at the SCI enough for saving my life. And of course, my beloved Dr Cheney, who knew better than anyone how sick I was … I feel such gratitude.

I was slipping into dementia from severe and unremitting CFS. I was desperate for help and when Dr Cheney invited me to go there in May, in my heart I knew I was going to get my life back. I was so sick that almost any quality of life was gone for me and I either wanted to die or get better. I was at the end of my rope as I was in constant and unrelenting pain, slipping away with dementia and fully bed-bound and home bound for several years after being vibrantly alive, loving life as an artist and a professor at the University of Minnesota, mother, wife and lover of life.

“I’ve regained peristalsis after 13 yrs. No more falling! No more chest pain, no more visits to the ER! I wake up the each day full of energy, not crashed. Thank you from the bottom of my heart… “

Although I state very enthusiastically my improvements, I still have a way to go; but because the improvements have been so marked I feel like there has already been an amazing transformation. Here are some of the improvements:

  • Anyone who speaks to me on the phone comments on how well I sound. Lately, I have heard in my voice an “authority” and sense of articulation that I once had when I was a professor and artist. My brain is healing and I have energy everyday. I still must rest most days but I want to get up and begin to rebuild my life. Incipit Vita Nova- Here begins the new life! I feel inspired! Before stem cells, I spoke often in a whisper as my vocal cord were weak and I would quickly tire, slur my speech and need to stop talking as it would exhaust me. I easily crashed from less than 10 minutes of phone conversation.
  • Comments from friends regarding getting well- ”woo yaa! Susan, you are lucid!” “You are back!…”look at you, your cognitive function is so much better.” I hear these comments everyday.
  • I was able to titrate from 40 mg to 5 mg of Cortef shortly after my 2nd visit to Panama. Now I plan to titrate off Cortef completely. With that, the bloating and weight gain is finally coming off my body.
  • I’ve regained peristalsis after 13 yrs.
  • No more falling! My balance is good and am able to climb out of, for example, a bath tub – I’m getting stronger! Falling was a constant worry and I did eventually fall and break my back recently. That was the final straw and I developed PTSD. I feel less pain now in the area of the herniated discs and I wonder if the stem cells will repair such injuries . Falling was a constant worry for my husband, there was a sense that my feet were not connected to my brain. Now that worry is in the past.
  • No more chest pain, no more visits to the ER! (15 visits last year!)
  • Fat turning into muscle, I can now stand up from a sitting position without the help of my arms pressing me up. My family comments on my form transforming.
  • Overall, more resiliency, vitality and cognitive improvement.
  • I am able to organize. I’ve been able to declutter and organize much of the piles of paperwork and miscellanea that have been piling up for a decade. . CFS made organizing impossible for me. I’ve heard that this is not uncommon.
  • I now have the energy to stay focused for 2 – 4 hrs at a time sitting in a chair doing paperwork or some task ( I have not had the strength to sit in a chair for 5 – 6 yrs. I wake up the each day full of energy, not crashed. Although I do feel muscle and joint pain from moving and so still need pain meds. But the most important thing is I rarely crash. I can be modestly active every day.
  • Memory! Although not perfect (I believe in part due to morphine) I am so much better. I can remember combinations of numbers on the spot. I know what I did the day before, the week before and what is planned in the future. I can remember what I wanted to do from day to day.

I am able to feel inspired and that is carried through the day to the next and the next. No amount of occupational therapy with strategies to support my memory ever worked. It’s hard to explain how far gone I was. I was lost to myself and I think it was the most terribly painful part of my experience of CFS. Regaining myself did not begin until after I was home from the 2nd stem cell protocol. And I am certain I needed the 30 day MS Protocol. None of these brain problems improved the first time and I could feel I was on a slow and disappointing slide backwards.

I wanted to thank you for all you have done for the benefit of myself and my family. My daughter, who moved home to help me out, has tears well up in her eyes regularly when she sees me interact with her in ways I haven’t since she was 14. You have been a bright light in the dark and desperate days of severe CFS. Thank you from the bottom of my heart from me and from that of my beautiful family, Chris and Christina.”

– S.L.

Stem cell therapy for rheumatoid arthritis: Kathleen Flores

“Since the treatment I have no pain; I feel really healthy and now I workout 3 times per week and I`m in better shape than I have been in years.”

I was diagnosed with Rheumatoid Arthritis by my rheumatologist 3 years ago. He wanted me to start some very strong drugs but I didn`t want them because I saw the secondary effects that they had on some of my friends that also have RA. I started searching for alternative options and thank God I found the stem cell treatment. Before my treatment I couldn`t walk without any help, could not climb stairs and I spent all day lying in bed because I felt sick.

After my first day of treatment I slept well, and after the 3rd and last treatment I was walking without any pain or help, it was amazing! Since the treatment I have no pain; I feel really healthy and now I workout 3 times per week and I`m in better shape than I have been in years. The Stem Cell doctors were wonderful with me and I highly recommend this treatment to any one with RA. The cost is not expensive compared to all the money I spent in meds and doctors before I got the stem cell treatment, in fact I save a lot of money.

Stem cell therapy for multiple sclerosis: Preston Walker

MS Stem Cell Patient Preston Walker

Preston Walker

A Different Approach

Sergeant Preston Walker
Courtesy Sergeant Preston Walker

After undergoing conventional therapy for MS for several years, Fort Worth police sergeant Preston Walker learned about a new therapy for autoimmune disorders. Researchers were utilizing adult stem cells derived from cord blood at The Institute of Cellular Medicine in Costa Rica. Walker inquired about the potential of using stem cells for multiple sclerosis.

“We knew that if the treatment worked, the potential benefits for multiple sclerosis patients could be limitless,” says Walker.

Dr. Neil Riordan, CEO of the Institute, suggested a therapy under consideration – using stem cells derived from a patient’s fat tissue. In May 2008, Walker flew to the clinic where doctors removed samples of his abdominal fat through a mini-liposuction, drawing out stem cells, which were later re-injected. According to Dr. Riordan, Walker and a colleague were the first to undergo this treatment protocol. “My quality of life has improved significantly,” Walker told the Post. “The problems with depression, fatigue, and balance have been corrected. I feel really good.”

In June 2009, Walker, who continues to take Avonex as a maintenance drug, plans a return trip to Costa Rica for a “tune-up,” as he puts it. “I’m curious to see if they can further improve my cognitive abilities.”

Fox 4 News: A Fort Worth police officer has returned from Central America after having a cutting edge medical procedure to help cure his multiple sclerosis. Last year we told you about Sergeant Preston Walker tonight Larry Barriger updates us on how he is feeling following his stem cell transplant.

Sergeant Preston Walker has always been active. With a demanding job at the Fort Worth Police Department, a wife, and young children, he doesn’t have time to slow down. But about 8 years ago he didn’t have a choice. MS started taking a toll making him limp when he walked, fatigue easily, even everyday conversation was a chore.

“I can sit here and talk but trying to come up with actual words to say and really construct a sentence that people would understand was sometimes very difficult.”

Medicine helped keep the disease in remission but Preston wanted more. A chance for a cure.

“I wasn’t prepared to just let it stay in remission without me trying to do something, especially if there is an option out there to address it.”

Sergeant Walker was initially planning to have his treatment done in China but he says the political situation seemed unstable, so he started looking online. He found another center that was doing adult stem cell treatment in Central America.

The procedure, a stem cell transplant was expensive but last October police officers from Fort Worth and Dallas teamed up to help raise money for the trip and the treatment. Last March Preston and fellow MS patient Richard Humphries flew to the Institute for Cellular Medicine, both underwent a stem cell transplant, a cutting edge medical procedure not approved in the US. Both took a risk on such a new treatment, both said they have seen marked improvement.

“I haven’t felt this good in 10 years. I don’t have any of the fatigue issues, all of the cognitive lack of clarity, that cloud has been lifted.”

Walker says doctors at the Institute will be keeping up with him and Richard over the coming months and years to determine how successful the treatment was. He is hoping his improvements last and that the research leads to a cure for his and other’s multiple sclerosis.

It seems like a pretty simple task for a police officer just sitting and working on a computer. Just a couple of years ago, multiple sclerosis made that almost impossible for Fortworth Police Officer Preston Walker. New at 6 CBS 11’s Joe Thomas says Walker credits friends for recovery some feel is a miracle.

A year ago Preston Walker did not think he’d still be in uniform. Walker found out he has multiple sclerosis. He suffered chronic fatigue and began losing use of his legs.

I felt like my cognition was really declining at a rapid pace. I really felt if I made it through the end of the year, last year, I probably wouldn’t be employed any longer because the cognition just wasn’t there.

His fellow police officers held a hockey-game fundraiser to help him afford a revolutionary treatment. Walker and another MS patient, Richard Humphreys, went to Costa Rica. For the first time ever, doctors took samples of their fat, drew stem cells from it, and reinjected it. Their symptoms nearly vanished.

I’ll suffer from any of those symptoms that we talked about, the depression, the fatigue, the little cognitive cloud. I mean it’ll still hit occasionally, but its no where near every day or every moment of every day like it was.

If we or somebody doesn’t become a guinea pig, then how can that benefit others?

They led the way to a treatment that is now helped ease the suffering of dozens of others. Joel Thomas, CBS 11 News.

Neil Riordan PhD – Stem cell therapy for spinal cord injury (part 3 of 5)

Mesenchymal stem cell homing to tissue damage, umbilical cord stem cells historically used for anti-aging, mesenchymal stem cells role in immune system modulation, inflammation reduction and stimulating tissue regeneration, donor stem cell safety and testing, the role of HLA matching in donated umbilical cord-derived stem cells, umbilical cord blood safety data and historical use in blood transfusions, allogeneic stem cell persistence in human mothers.

Adult stem cell therapy for rheumatoid arthritis and osteoarthritis: Neil Riordan, PhD

Dr. Riordan discusses focuses on mesenchymal stem cells harvested from fat tissue and the role they play in reducing inflammation, repairing tissue and modulating the immune system.