Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study.

Int Orthop. 2014 Sep;38(9):1811-8. doi: 10.1007/s00264-014-2391-1. Epub 2014 Jun 7.

Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H.

Abstract

Rotator Cuff

Rotator Cuff

PURPOSE:  The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface.

METHODS:  Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up).

RESULTS:  Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval.

CONCLUSION:  This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.

2015-09-28T19:47:55+00:00September 28th, 2015|Bone Marrow Stem Cells, News, Rotator Cuff|

What are the sources of the stem cells used at Stem Cell Institute in Panama?

Lately, especially on our Facebook Page many people are asking us, “What is the source of the stem cells?”

Stem cells under fluorescent microscope.At the Stem Cell Institute, we use two types of stem cells. Primarily, we use allogeneic mesenchymal stem cells harvested from human umbilical cord tissue. In addition to allogeneic mesenchymal stem cells, our spinal cord injury protocol uses autologous (patient’s own) stem cells harvested from bone marrow.

Umbilical cord tissue is donated by mothers after normal, healthy births.

All donating mothers are tested for infectious diseases and have their medical histories screened. We obtain proper consent from each family prior to umbilical cord donation.

All mesenchymal stem cells harvested from umbilical cords are screened for infectious diseases to International Blood Bank Standards before they are approved for use in treatments.

A small number of umbilical cords (about 1 in 10) pass our rigorous screening process.

Dr. Riordan on the Umbilical Cord Selection Process at Stem Cell Institute

“Through retrospective analysis of our cases, we’ve identified proteins and genes that allow us to screen several hundred umbilical cord donations to find the ones that we know are most effective. We only use these cells and we call them ‘golden cells’.

We go through a very high throughput screening process to find cells that we know have the best anti-inflammatory activity, the best immune modulating capacity, and the best ability to stimulate regeneration.”

What are the advantages of treating with allogeneic human umbilical cord tissue (HUCT)-derived mesenchymal stem cells?

  • Anyone can be treated since HUCT mesenchymal stem cells are immune system privileged. Human Leukocyte Antigen (HLA) matching is not necessary.
  • The stem cells with the best anti-inflammatory activity, immune modulating capacity, and ability to stimulate regeneration can be screened and selected.
  • Allogeneic stem cells can be administered multiple times over the course of days in uniform dosages that contain high cell counts.
  • Umbilical cord tissue provides an abundant supply of mesenchymal stem cells.
  • No need to collect stem cells through invasive procedures such as liposuction or bone marrow collection
  • There is a growing body of evidence showing that mesenchymal stem cells from umbilical cords are more robust than mesenchymal stem cells from other sources such as fat.

The body’s immune system is unable to recognize human umbilical cord tissue (HUCT)-derived mesenchmyal stem cells as foreign and therefore they are not rejected. HUCT stem cells have been administered thousands of times at the Stem Cell Institute and there has never been a single instance rejection (graft vs. host disease). Umbilical cord-derived mesenchymal stem cells also proliferate/differentiate more efficiently than “older” cells, such as those found in the fat and therefore, they are considered to be more “potent”.

Watch Professor Arnold Caplan from Case Western Reserve University explain how this works.

PRESS RELEASE – UCLA Wide Receiver and Canadian Decathlon Standout Zack Bornstein Bounces Back After Stem Cell Therapy at Riordan-McKenna Institute

MRI confirms complete healing of hamstring eight weeks after Dr. Wade McKenna administered guided injections of bone marrow aspirate concentrate (BMAC) harvested with BioMAC (patent pending) bone marrow aspiration cannula and AlphGEMS amniotic tissue product at the Riordan-McKenna Institute.

DALLAS-FORT WORTH, TEXAS (PRWEB) SEPTEMBER 03, 2015

Zack Bornstein with Dr. McKenna and Physicians Assistant, Troy Chandler

Zack Bornstein with Dr. McKenna and Physicians Assistant, Troy Chandler

UCLA wide receiver and Canadian decathlon standout, Zack Bornstein suffered a hamstring tear 18 months ago. Conventional treatment and therapy were not working so Zack decided to undergo stem cell therapy at Riordan-McKenna Institute in late June 2015. Dr. McKenna treated Zack with precisely guided injections of bone marrow aspirate concentrate (BMAC) harvested with the BioMAC (patent pending) bone marrow aspiration cannula and *AlphGEMS amniotic tissue product.

Complete healing was confirmed by MRI 8 weeks after treatment:

1) No evidence for hamstring strain or denervation and no evidence for tendon tear.
2) No evidence for focal atrophy or hematoma.
3) No osseous abnormalities seen.

After receiving the MRI results, Zack’s father Dean said, “I am not a doctor but looks like you and your procedure has performed a medical miracle! …Thanks for all of your efforts.”

Zack is currently a red shirt freshman at UCLA. He played football at Oaks Christian High School from 2011-’14 and lettered 3 years in football and all 4 years in track. In 2013, Zack was named to the All-Marmonte 2nd team. He played in the FBU Youth All-American game in 2010. In track, he is considered to be one of the top decathletes in the country. Zack competed at the 2013 Pan American Junior Championships in Medellin, Columbia, finishing in 5th place with 7,097 points. In July of 2013, he became the Canadian Junior National Champion (6,918 pts). Zack won the silver medal at the 2013 Arcadia Invitational Decathlon, scoring 6,967 points to set a new California state record for juniors (2nd highest score in California state history). Zack is a 12-time National Champion, 44-time All-American and a member of three National Championship cross country teams.

About Riordan-McKenna Institute (RMI)

RMI specializes in non-surgical treatment of acute and chronic orthopedic conditions using *AlphaGEMS flowable amniotic tissue allograft and bone marrow aspirate concentrate (BMAC) that is harvested using the patented BioMAC bone marrow aspiration cannula. Common conditions treated include meniscal tears, ACL injuries, rotator cuff injuries, runner’s knee, tennis elbow, and joint pain due to degenerative conditions like osteoarthritis. RMI also uses AlphaPATCH amniotic membranes as part of a complete wound care treatment regimen.

RMI also augments orthopedic surgeries with BMAC and AlphaGEMS to promote better post-surgical outcomes.
BMAC contains a patient’s own mesenchymal stem cells (MSC,) hematopoietic stem cells (CD34+), growth factors and other progenitor cells. AlphaGEMS is composed of collagens and other structural proteins, which provide a biologic matrix that supports angiogenesis, tissue growth and new collagen during tissue regeneration and repair.

*AlphaGEMS and AlphaPATCH products are produced by Amniotic Therapies Inc. from donated amniotic tissue after normal healthy births. For more information about AlphaGEMS, please visit: http://www.rmiclinic.com/non-surgical-stem-cell-injections-joint-pain/stemnexa-protocol/

http://www.rmiclinic.com

801 E. Southlake Blvd.
Southlake, Texas
76092

Tel: (817) 776-8155
Toll Free: (877) 899-7836
Fax: (817) 776-8154

About Amniotic Therapies

Based in Dallas, Texas, Amniotic Therapies specializes in the processing and distribution of human amniotic tissue products for the biologic and regenerative medicine segments of the healthcare market. Amniotic Therapies’ mission is to provide superior human amniotic tissue products that naturally enhance the body’s healing ability, providing patients with improved healing.
Amniotic Therapies is registered with the U.S. Food and Drug Administration (FDA) and is in the process of receiving accreditation from the American Association of Tissue Banks.

http://www.amniotictherapies.com

11496 Luna Rd. Suite 800
Dallas, Texas
75235

Tel: (972) 465-0496

Neil Riordan PhD – on opening a stem cell clinic in the United States

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 for Dr. Riordan: If the FDA loosens regulations in the U.S., do you have any plans to open a clinic here?

Dr. Riordan’s Answer: Unfortunately I don’t see FDA loosening regulations any time soon so I have no plans to do anything in the U.S. using umbilical cord MSCs or even autologous SVF in the near future.

It would be great if the U.S. would follow Japan’s lead. The Japanese parliament passed legislation in November of last year that essentially allows a company to market a cell product after the product has been demonstrated to be safe. Quoting from an Athersys press release: “Recently, Japan’s parliament enacted new legislation to promote the safe and accelerated development of treatments using stem cells. The new regenerative medicine law and revised pharmaceutical affairs law define products containing stem cells as regenerative medicine products and allow for the conditional approval of such products if safety has been confirmed in clinical trials, even if their efficacy has not been fully demonstrated.”

So you can guess where everyone is running to and isn’t the U.S. Here are press releases from Mesoblast and Athersys, respectively:


http://globenewswire.com/news-release/2013/11/25/592037/10059311/en/New-Japanese-Regenerative-Medicine-Legislation-and-Commercial-Opportunities-for-Stem-Cell-Products.html

http://finance.yahoo.com/news/athersys-announces-patents-japan-stem-120000430.html

Regarding plans for the U.S., I have thankfully partnered with Dr. Wade McKenna, who is Board Certified in Orthopedic surgery and Fellowship trained in Trauma and Trauma Reconstructive Surgery. Dr. McKenna has more experience using bone marrow concentrate for orthopedic conditions that anyone I know. We are opening a regenerative orthopedic center in the Dallas area hopefully by mid-April of this year. It will be in a new building and is being built out now. The center is called the Riordan McKenna Institute. It is located in Southlake, Texas, which is between Dallas and Ft. Worth, very near DFW airport.

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation: A case report on a chronically injured man with quadriplegia

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation - A case report on a chronically injured man with quadriplegia

Daniel Leonard in Panama

This is a research paper written by Rebecca Johnston, Daniel Leonard’s sister. She recently graduated from a Physical Therapy degree program, and wrote her Capstone paper about Daniel’s stem cell therapy treatment in Panama.

Daniel is presented anonymously in the paper, but Rebecca and Daniel have given their permission for this paper to be shared. Daniel’s ASIA scores (pre and post treatment) are in the appendix of this paper.

 

Allogeneic and autogolous stem cell therapy combined with physical rehabilitation: A case report on a chronically injured man with quadriplegia

Abstract:

Background and Purpose: Stem cell therapy for SCI is a potentially promising treatment with increasing interest. This case report describes the use of a particular stem cell therapy protocol for a patient with chronic spinal cord injury, and describes his subsequent therapy and outcomes.

Case Description: The patient is a 29-year-old male who is chronically injured from a cervical spinal injury, resulting in quadriplegia. The patient was treated with a combined protocol of intrathecal (IT) and intravaneous (IV) allogeneic MSC and CD34+ cells and IT autologous BMMC at 6 ½ years post-injury. The results track the patient’s physical therapy progress until 6 months following stem cell treatment.

Outcomes: Recovery of strength in upper extremity and lower extremity muscle groups was noted, along with a functional increase in grip strength, ability to ambulate with assistance, and a significant decrease in daily medications.
Discussion: This case supports further investigation into treatment of chronically injured SCI patients with stem cell therapy followed by physical therapy.

Manuscript word count: 4321

A few highlights:

“After the patient underwent the stem cell treatment and returned to outpatient physical therapy in his hometown clinic in the United States, his MMT scores were tested over the period of 5 months post-stem cell treatment…. The patient did not decrease in strength in any of the muscles tested, and experienced improvements in 6/13 upper extremity muscle groups, and 8/9 lower extremity muscle groups.”

“The patient also had an increase in grip strength. His grip strength was measured by his occupational therapist to be 5 lbs on the right and 25 lbs on the left at one month before his stem cell treatment. Six months later, his grip strength was measured to be 22 lbs on the right and 36 lbs on the left. The patient reported that this increase in grip strength led to functional improvements, such as being able to self-catheterize, which he was completely unable to do since his injury.”

“The patient was also able to ambulate for the first time in 5 years at approximately 4 months after finishing his treatment. He was able to ambulate in partial weight bearing with the harness and max assist of two for 40 yards at .5 MPH.”


The original post on Daniel Leonard’s blog can be found here.

Bone Marrow Stem Cells Significantly Improve Cardiac Mortality Rate in Heart Disease Patients

Texas Heart Institute researcher, Emerson Perin MD, PhD revealed that heart patients who were treated with bone marrow-derived adult stem cells died at a significantly lower rate that those who did not receive stem cells. Dr. Perin’s scientific findings represent yet another positive step in the ongoing fight against heart disease.

Dr. Perin is the Director of Clinical Research for Cardiovascular Medicine and Medical Director for the Stem Cell Institute at the Texas Heart Institute in Houston, Texas. Dr. Perin’s study showed that patients treated with stem cells were 90% less likes to die from an adverse cardiac event than patients who were not treated with stem cells.

“We obtained remarkable results from our study in which we injected stem cells derived from the bone marrow of a healthy donor into patients with heart failure. Heart function and exercise capacity improved in some cell-treated patients. Most importantly, cell therapy significantly reduced cardiac adverse events, including death. Three of 15 (20%) control patients died of cardiac causes, whereas only 1 of 45 (2%) cell-treated patients had a cardiac-related death. Despite the small numbers, our findings showed that cell therapy significantly improved cardiac mortality,” said Dr. Perin.

2012-01-25T18:44:01+00:00January 25th, 2012|Adult Stem Cells, Heart Disease, News, Stem Cell Research|

Excerpts from Interview with Dr. Amit Patel, Director of Regenerative Medicine, University of Utah by Thomas Ichim, Ph.D, CEO of Medistem Inc

www.thelatestwith.com

Ichim: Which one was the first stem cell trial for cardiac conditions?

Patel: It is like one of those questions like who did the first heart operation. There is a lot of debate as to what was the first to use cells plus therapy and there have been a number of trials. Myoblasts were performed in 2000, the Chinese reported work performed in 1999 or 2000, and the Ralfstock guys in Germany 2000s. So there are a number of trials, including ours, all in the 2000-2003 period that where being conducted almost simultaneously.

Ichim: Pardon me for asking because I should really know this, which one was yours?

Patel: The original CABG plus cells, which was performed in South America and India.

Ichim: Lets talk about Phase 2 trials in cardiac, we all have seen the excellent co-development deal between Cephalon and Mesoblast that happened in December of last year and we are all interested in how far are they?

Patel: The Cephalon-Mesoblast work is interesting. They are doing a 60 patient randomized trial here in the US in patients with Class II-IV heart failure. From the data thus far released there is a significant reduction in treatment group in terms of adverse events as compared to the placebo control group, they have not reported any efficacy data in terms of ejection fraction and the like.

Something unique from the data they presented was that they showed up to 2/3 of the control group were class III heart failure and 2/3 of the treatment group were class II. The early data was very interesting and promising. The safety of the data was very eloquent and reproducible. One thing that was very unique was Erik Dukker’s European large animal acute MI data which was the best in terms of scar reduction for any allogeneic MSC that I have seen to date. That data, if it pans out, in humans will be very interesting.

Ichim: How did Mesoblast administer their cells? Did they use balloon catheter in the heart failure patients?

Patel: They used NOGA mapping and administration, in chronic heart failure, both ischemic and non-ischemia. They did not do acute myocardial infarction in this trial.

Their trial had similarities with our Phase II Aastrom, which also uses NOGA administration in treatment of patients with ischemic and non ischemic heart failure. It is different in that we were looking only at class III/IV heart failure.

Ichim: How is that trial coming along?

Patel: Ours is completed from the patient recruitment and treatment perspective.

We are waiting 6 month data. Our trial was a three center trial between myself, Tim Henry and Mark O’Costa. These three centers were heavy enrollers. We had low adverse events so far. This study involves patient’s own bone marrow stem cells expanded for 12 days using Aastrom’s proprietary bioreactor system.

Ichim: Lets go back to my question about Mesoblast. Remember we were chatting at the meeting about this. There seems to be a lot of different players in this field that are all using bone marrow derived stem cells. Obviously I believe endometrial derived stem cells possess numerous advantages. But there is Osiris’s mesenchymals, there is Athersys who are using Catherine Verfaille’s cells that seem to be like mesenchymal stem cells except for their smaller size. What is the cell that Mesoblast is using? Are they just another type of mesenchymal stem cell?

Patel: By name they call them the cells mesenchymal precursors. The Mesoblast cells are unique in that they express STRO-1 and VLA-4.

In my opinion everyone’s stem cells have unique properties and surface markers be they Osiris, Mesoblast, Athersys, Allocure, and a couple other products that are bone marrow based.

What is unique to see will be the IP landscape, are they same cells or cousins? This may be a situation like the CD133 versus CD34. In this field we know that all mesenchymal stem cells are not the same but the question will be how similar or different are they when you apply them clinically?

Ichim: Did we forget to mention any other ones?

Patel: I am sure that we did, but not for want to miss them but just because they have not made enough noise. Actually the one trial we forgot to discuss was the Athersys phase I which Warren Sherman from Columbia presented using the Cricket catheter, which is adventitial delivery, that was a very safe trial. It will be interesting to see how they do in the next generation for their phase II AMI study.

Ichim: That was very interesting. That was the one with the bizarre catheter that actually had a couple of needles in it?

Patel: That catheter had one needle, it causes a microperforation to allow for perivascular injection. This is a very innovative concept since people that use the standard intracoronary delivery techniques seem to have a lot of washout of the cells.

Ichim: I don’t get it. So they are making a small hole in the blood vessel, why is it that there is no bleeding or damage?

Patel: The microperforation is way too small. You do not perforate into the pericardium. It only barely perforates. However it does require a well highly trained skill set to manipulate that catheter. If you had been listening to Dr. Sherman’s presentation you would have seen that there were no catheter-related injuries.

Ichim: (Laughing). OK, what about the large Brazilian data? That was also a session that I didn’t listen through in entirety.

Patel: That data was 10 year follow-up on several Brazilian studies. The work was initially performed in heart failure using NOGA by Hans Doneman, then they had Emerson Perin and Jim Willerson. We also had our work which involved CABG. That was groundbreaking work that set the foundations for a lot of the cardiac cell therapy that is being performed today. We are still waiting to hear the outcomes of the studies that were funded by the government of Brazil including the work on Chagas, dilated cardiomyopathy, and CABG.

Ichim: Speaking of South America, what did Jorge Tuma present?

Patel: This was incredible data that had patients who have been followed for 8 years. Cell administration was performed via the retrograde technique which we developed with him. The original experiments involved bone marrow mononuclear cells isolated by ficoll, heap-starch, CD34, etc, he is now using the Harvest system for autologous bone marrow mononuclear cell collection. He presented data on ten patients treated with this.

Ichim: This is what I love about interviews, I can ask all sorts of questions about things that I should know but I don’t. What exactly is this “retrograde technique”? I have heard you mention it several times.

Patel: We access the venous system of the heart. We occlude the outflow and deliver the biologic into the heart. What is unique is that the venous system does not get the same atherosclerosis as the arterial system. This procedure has been around since 1898..its been around from back then…the idea was can we give oxygenated blood back to the heart. It was in the 50s and 60s when Illahi started to implement this. I use this in my heart operations to give chemicals and nutrients into the heart backwards during open heart operations…so I said how

Administration of cells using the retrograde technique takes me half hour to do. This appears to be a safe and cost efficient means to deliver a biologic to the heart on incredibly sick patients.

Ichim: To put in things in perspective regarding cell administration. I know that NOGA is expensive and not too many centers have it. But how long does it take to do a NOGA administration of stem cells into the heart?

Patel: 1-2.5 hours, usually 90 minutes at best, you are manipulating the inside of the heart so there is a risk of irregular rhtyums, also low risk of perforation

Ichim: I still don’t really understand this retrograde technique. How is it that the cells actually enter the heart? Do they actually cross into the tissue?

Patel: You block the outflow of the heart and under pressure you push the cells into the venous system. So you have created a column of cells. You have antegrade blood flow and retrograde stop flow, so the cells either go into the tissue or perforate the sinus…perforate the sinus is very rare, less than 1 % in over a couple hundred patients. These are microperforations in the venous system so it doesn’t require emergent surgery…all of the patients in which this has occurred have done well.

Juventas presented some data in large animals in which the SDF plasmid showed a significant uprgulation using retrograde techniques in contrast to other means of delivery.

Ichim: To switch topics I saw you on CNN about spraying stem cells on poor patients with bad burns, how do the cells go inside of the tissue?

Patel: We add calcium and thrombin, it looks like jello if you were to spray it into the petri disue, so you have retention by tissue adhesion and the mechanical properties of the collagen, thrombin and calcium, so you are creating a matrix for your biologic. So it really is spray on and it actually sticks there.

Ichim: I remember you now based in Utah, what ever happened to that company in your neck of the woods Allocure? How are they doing these days?

Patel: The last I heard they completed Phase I trial here in Utah, they were giving at the time of heart surgery for renal production. They have a bone marrow mesenchymal cell product. The trial is completed, we are looking to see what their next study will be. Will the stick to renal protection or will they follow other companies by entering CLI, heart failure, etc.

Ichim: You know, I was impressed by that company C3 or something like that, they were using differentiated cells for heart?

Patel: That was a Phase I/II trial by Joseph Bartnak where they have a bone marrow mesenchymal cell that was cultured in a procardiac cocktail. It was administered by noga or endocardial mapping. And again the data looked interesting…we look forward to their next trial and when they come to US

Ichim: What they were doing was really new in my humble opinion. It seems to me like everyone in this field is administering undifferentiated cells based on the belief or hope that the damaged tissue will program the undifferentiated stem cell to become a cardiomyocyte. To your knowledge are there other people using differentiated or semi-differentiated cells?

Patel: Yes of course. There is Capricor, Eduardo Marban’s company. They are taking a biopsy of the patient’s own heart, grow up the cells and put them back in. They don’t put the cardiospheres back in because they are too large but put in some cells derived from cardiosphere grown in vitro. One of the issues they are facing is that their procedure is very much dependent on the starting material. They were able to do biopsy but because there was large variability in the weight of the starting tissue, it is important to figure out how to get enough

Ichim: Conceptually it seems counter-intuative to take out heart from a patient with heart failure !

Patel: People do right heart biopsy in transplant patients, doing native heart biopsy you are always concerned about damaging the valve. Raj who was doing the procedure for them is a great interventionalist, but have to make sure that the procedure is designed so that other interventionalists who may not have his skill set can do it. The concept is great but manufacturing and reproducibility is important.

2012-01-12T21:10:18+00:00January 12th, 2012|News|

Stem Cell trial volunteers thank doctors at reunion lunch

Miami Herald, by Fred Tasker, ftasker@MiamiHerald.com
Stem cell therapy was originally used for the treatment of leukemias in the form of bone marrow transplant. Nearly 2 decades after this groundbreaking work, clinical trials initiated using bone marrow stem cells for treatment of heart patients. Bone marrow stem cells possess the ability to stimulate new blood vessel formation, a process called angiogenesis, which is essential in: a) accelerating healing after a heart attack; and b) in patients who have angina, stimulating new blood vessels to grow and take over the function of the clogged arteries that are causing the angina.
Initial work in this area involved administering stem cells from the bone marrow that were non-purified, directly into the heart muscle. Subsequently new techniques were developed so that open heart surgery was not needed. These techniques include the use of catheter-based delivery systems. Additionally, scientists found that one type of stem cell that is found in the bone marrow, called the mesenchymal stem cells, is actually more potent than bone marrow non-purified cells. Clinical trials have been performed with mesenchymal stem cells for heart failure. One of the major ones involved intravenous administration of “universal donor” cells. This article describes some of the patients that participated in Osiris’ 51 patient clinical trial.
“I believe in miracles, God — and my doctors,” said Edgar Irastorza, 33, the youngest of 51 patients at the luncheon.
Early results are promising, says Hare, director of UM’s Interdisciplinary Stem Cell Institute.
“We don’t know what the results will be, but things are going well. The fact that you’re here is testament to that,” he told the patients, united for the first time at a luncheon titled “Heart of a Pioneer” to celebrate their struggle.
Irastorza, a Miami property manager, said he died briefly on Oct. 6, 2008. A genetic defect gave him such a serious heart attack that his heart stopped for a few minutes. Doctors who revived him said half his heart was dead and warned him to prepare for a short, disabled life. They wanted to insert a defibrillator into his chest.
“I didn’t want that,” he said. “I didn’t want to give up sex and dancing.”
On March 3, 2010, UM doctors used a catheter inserted through a slit in his groin to inject millions of tiny stem cells into his damaged heart.
At the Friday luncheon, Irastorza presented to the crowd a five-minute video of his new self, doing an energetic, head-spinning break dance.
“I’m not completely back to normal, but, compared to before, it’s night and day,” he said.

Felix Morales, 80, a retired agriculture worker, had a heart attack 25 years ago and recently had become too easily fatigued to take care of the collards and peppers and the mamey and mango trees in his Miami backyard.
A year ago, he got one of the stem-cell treatments. “It took a while, but I feel good right now,” he said. “I have no words to express my gratitude.”
Evangeline Gordon, 40, a state probation officer from Miami, called 911 one October night in 2009, thinking she had a bad gas attack. To her shock, doctors told her a heart attack had damaged 70 percent of her heart muscle. They began discussing a heart transplant.
Instead, she volunteered for the UM program and got stem cells from a donor. Like most of the others, she doesn’t know if she got real stem cells or a placebo treatment used for comparison.
“I’m up and down,” she said Friday. “I still get angina and fatigue, but I don’t feel like I’m going down anymore.”

2011-04-29T19:37:28+00:00April 29th, 2011|Clinical Trials, News, Stem Cell Research, Stem Cell Therapy|

New Stem Cells Found in Ovary

Parte et al. Stem Cells Dev.

Very small embryonic like cells (VSEL) are a type of stem cell that appears to be found in bone marrow and other tissues of the body, presumably as a remnant of embryonic or embryonic-like cells left over from development. In a recent paper it was demonstrated that these cells may be found in the ovary surface epithelium in adult rabbit, sheep, monkey and menopausal human.

Indian scientists found two distinct populations of putative stem cells of variable size were detected in the ovary surface epithelium: one being smaller in size around the range of 1-3 micrometers and the other being of a size approximate to the surrounding erythrocytes.

The smaller cells resembled VSELs and were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4. The larger cells were 4-7micrometers and possessed cytoplasmic localization of Oct-4 and minimal expression of SSEA-4. The scientists believed that the larger cells were possibly the progenitor germ cells.

The VSEL cells were capable of spontaneously differentiating into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype and embryonic stem (ES) cell-like colonies. They expressed Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 as detected by RT-PCR.

Germ cell markers like c-Kit, DAZL, GDF-9, VASA and ZP4 were immuno-localized in oocyte-like structures formed from the VSEL.

These studies are interesting because prior to this there were reports of bone marrow derived cells being implicated in production of oocytes. Specifically, Jonathan Tilley from Harvard reported that bone marrow transplantation can give rise to new oocytes that are donor derived http://www.ncbi.nlm.nih.gov/pubmed/17664466.

If these studies are reproducible it may be that adult stem cells could be useful in the treatment of infertility. Conversely it may be possible to repair oocytes of women who have undergone chemo/radiation therapy. Interestingly, Tilly’s group also published that ovarian tissue contains VSEL-like cells http://www.ncbi.nlm.nih.gov/pubmed/20188358

2011-02-03T20:42:13+00:00February 3rd, 2011|News, Stem Cell Research|

Mechanisms of a New Stem Cell Mobilizer

Jarcome-Galarza et al. J Bone Miner Res.

It is known that the bone marrow contains three main types of stem cells: a) hematopoietic stem cells, which make blood; b) endothelial progenitor cells, which maintain healthy blood vessels; and c) mesenchymal stem cells, which repair a variety of tissues and are capable of producing high amounts of growth factors. After major tissue injury or trauma all three of the bone marrow derived stem cells leave the bone marrow and enter systemic circulation in an attempt to heal the tissue damage. The original compound that was discovered to “mobilize” bone marrow stem cells was granulocyte colony stimulating factor (G-CSF). Studies in mice with lung injury in the late 1970s demonstrated that a lung-derived protein was capable of stimulating bone marrow to multiply and produce higher numbers of granulocytes. It was not until the late 1980s that scientists started injecting purified G-CSF into animals as a method of increasing the number of circulating stem cells. Why would people want to increase circulating stem cells? Commercially one of the main reasons is associated with the process of bone marrow transplantation. In bone marrow transplantation donors were historically required to undergo the painful procedure of bone marrow extraction, which requires an excess of 20 holes to be drilled into their hip bones. Compounds such as G-CSF could be administered to donors in order to make their stem cells enter circulation, and then the stem cells could be isolated from the blood instead of the bone marrow. This makes the procedure a lot less painful and arguably a lot safer. Additionally, the possibility of mobilizing stem cells by administration of a drug has the possibility of artificially increasing stem cell numbers in patients with degenerative diseases in order to attempt to naturally heal the condition.

The clinical use of G-CSF for mobilization and also for increasing granulocytes in the blood has resulted in multibillion dollars per year in sales for companies such as Amgen. Naturally, this has stimulated much interest in the process of how to make stem cells leave the bone marrow. G-CSF stimulates bone marrow stem cell release through several mechanisms. The main mechanism appears to be associated with stimulation of osteoclasts, which cause modulation of the bone marrow structure and physically release the stem cells from their environment. Other mechanisms exist such as breakdown of stromal derived growth factor (SDF-1). This protein is made by the bone marrow and literally keeps the hematopoietic stem cells stuck to the bone. When the bone marrow levels of SDF-1 decrease, the hematopoietic stem cells are no longer “stuck” to the marrow and as a result enter circulation. Yet another mechanism is that G-CSF activates neutrophils to produce various enzymes that cleave proteins on the bone marrow. These cleaved proteins are then recognized by pre-formed antibodies, which activate complement, which causes small holes in the bone marrow and thus releases stem cells.

The second “stem cell mobilizer” to be approved by the FDA is a drug called Mozibil which blocks the interaction between SDF-1 and its receptor CXCR4. This drug was sold by Anormed to Genzyme in a deal worth more than half a billion dollars. Mozibil is a superior stem cell mobilizer to G-CSF in many patients and as a result has rapidly been implemented clinically. Interestingly, it appears that Mozibil causes redistribution of different ratios of hematopoietic, mesenchymal and endothelial progenitor cells than G-CSF.

One of the most recent mobilizers under development is Parathyroid Hormone. This naturally –occurring substance has been demonstrated in clinical trials to mobilize stem cells, but apparently through a mechanism different than G-CSF and Mozibil. Specifically, both of these drugs appear to cause a temporary depletion of the stem cells in the bone marrow, whereas Parathyroid Hormone seems to preserve the stem cells inside of the bone marrow.

A recent paper (Jacome-Galarza et al. Parathyroid hormone regulates the distribution and osteoclastogenic potential of hematopoietic progenitors in the bone marrow. J Bone Miner Res. 2010 Dec 29) explored the activities of Parathyroid Hormone on osteoclasts in the bone marrow of mice. The authors found that treatment of mice with Parathyroid Hormone for 7 or 14 days increased the number of osteoclastic progenitors in the bone marrow as well as the absolute number of hematopoietic progenitors. These data suggest that the hormone acts not only as a means of stimulating redistribution of hematopoietic stem cells, but also may be involved in directly stimulating their multiplication, possibly through modulating activity of osteoclasts.

2010-12-29T21:28:33+00:00December 29th, 2010|News, Stem Cell Research|