Multiple Sclerosis Radio – “Stem cells are your body’s natural healing mechanism” – Neil Riordan PhD

For anyone who missed Dr. Riordan’s talk on MS Radio yesterday, below is a link to the replay. Did you know that by age 30, 96% of the mesenchymal stem cells are gone from a person’s bone marrow? Why is MS a disease of the immune system? How can an automated machine analyze a sample of lecithin and buffer that contains no cells and show that it contains 10 million cells per ml? Tune in for these and more.

REPLAY: “Stem cells are your body’s natural healing mechanism” – Neil Riordan PhD

TODAY ON MULTIPLE SCLEROSIS RADIO!
Dr. Neil Riordan, Founder of Stem Cell Institute
Tuesday Feb 5, 2013 at 2 pm EST.

LISTEN ONLINE: Multiple Sclerosis Radio

or call in Join Us LIVE On Air
(347) 327-9317
or Toll-Free
(877) 497-9936

http://www.blogtalkradio.com/msradio/2013/02/05/stem-cells-your-bodys-natural-healing-mechanism-stem-kine-1

Patients beware: “Point of care” fat stem cell separation and counting kits inaccurate and not US FDA approved for humans.

An informative paper by Mary Pat Moyer, PhD detailing why “same-day” fat stem cell kits that are becoming more common in doctors’ offices across the US can miscount “stem cells” by large factors leading to over estimation of stem cell counts by as much as 20 times or more.

It also states, “no complete harvest and cell isolation systems have been approved by the FDA for autologous SVF harvest for immediate use [in humans].” These are just a couple of the arguments presented that demonstrate why it’s important to process adipose tissue properly in a professional lab setting.

Morrison DG, Hunt DA, Garza I, Johnson RA, Moyer MP*. Counting and Processing Methods Impact Accuracy of Adipose Stem Cell Doses. BioProcess J, 2012; 11(4): 4-17.

2013-01-22T23:15:25+00:00January 22nd, 2013|Adipose Stem Cells, Adult Stem Cells, News, Stem Cell Research|

Medistem Advances Type 1 Diabetes Stem Cell Technology Licensed From Yale

SAN DIEGO, CA — (Marketwire) — 09/12/12 — Medistem Inc. (PINKSHEETS: MEDS) announced today completion of the first phase of a joint project with the Shumakov Research Center of Transplantology and Artificial Organs of the Russian Federation and its Russian and CIS licensee ERCell. The collaboration is based on using Endometrial Regenerative Cell (ERC) technology licensed from Yale University to treat type 1 diabetes.

Dr. Viktor Sevastianov, Head and Professor of the Institute of Biomedical Research and Technology, within the Shumakov Center, demonstrated safety and feasibility of ERC injection in experimental animal models of diabetes. Additionally, the studies demonstrated that the cell delivery technology developed by Dr. Sevastianov’s laboratory can be used to enhance growth of ERC. These experiments are part of the process for registration of “new pharmacological substances,” which is the first step towards drug approval in Russia.
“Type 1 diabetes is a significant problem in the Russian Federation. Our laboratory has been working developing various delivery formulations for cell therapy, such as SpheroGel, which is registered in Russia,” said Dr. Sevastianov. “Given that the ERC can be produced in large quantities, is a universal donor cell, and already is approved for clinical trials in both the USA and Russia, we are optimistic our collaboration will lead to a viable commercial product for the type 1 diabetes Russian population.”
Medistem discovered ERCs in 2007, and they appear to possess “universal donor” properties, allowing the cells derived from one donor can treat multiple unrelated recipients. According to Medistem’s current FDA cleared production scheme, one donor can generate 20,000 patient doses. Medistem licensed technology from Yale University for generating insulin producing cells from ERC. A publication describing the technology may be found at http://www.ncbi.nlm.nih.gov/pubmed/21878900.

“Our vision is to combine SpheroGel, which is a clinically-available cell delivery vehicle in Russia, together with Medistem’s ERC and technology from Yale University to generate a commercially-viable product for clinical trials in type 1 diabetes patients,” said Thomas Ichim, CEO of Medistem.

Medistem has outlicensed the Russian and CIS rights to ERC and related products to ERCell LLC, a St. Petersburg-based biotechnology company. Under the agreement, Medistem owns all data generated and will receive milestone and royalty payments.
“By working with leading investigators in Russia and the USA, we seek to be the leaders in a new era of medicine in Russia,” said Tereza Ustimova, CEO of ERCell.”

Cautionary Statement This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Contact: Thomas Ichim Chief Executive Officer Medistem Inc. 9255 Towne Centre Drive Suite 450 San Diego, CA 92122 858 349 3617 www.medisteminc.com twitter: @thomasichim
Source: Medistem Inc.

2012-09-13T17:37:45+00:00September 13th, 2012|Diabetes, News, Stem Cell Research|

Blood Stem Cells Permanently Damaged by Alcohol

Bone marrow stem cells are extremely sensitive to the primary by-product of alcohol, which causes permanent damage to their DNA claims researchers from the Medical Research Council (MRC) Lab of Molecular Biology.

The research, which was conducted on mice, uncovers two mechanisms that normally control this type of damage; a protein group that recognizes and repairs DNA damage and an enzyme that eliminates acetaldehyde, alcohol’s toxic breakdown product.

Mice lacking both protective mechanisms developed bone marrow failure stemming from blood stem cell damage.
These results mark the first time that scientists have been able to explain why bone marrow fails in Fanconi anemia (FA) patients. FA is a rare genetic disorder.

The report concludes that FA turns off the bone marrow’s “repair kit” via FA gene mutation which causers DNA damage from acetaldehyde to continue unchecked. This damage is responsible for bone marrow failure and developmental defects in FA patients and makes them especially vulnerable to blood and other types of cancer.

These findings may have particular significance for the world’s Asian population, many of whom suffer from “Asian flush syndrome”. People with AFS lack the enzyme ALDH2 and therefore could be particularly susceptible to DNA damage. The authors warned that this subset of the Asian population could suffer permanent DNA damage with alcohol consumption and be more highly prone to blood cancer, bone marrow failure and premature aging than the Asian population at-large.

“Blood stem cells are responsible for providing a continuous supply of healthy blood cells throughout our lifespan. With age, these vital stem cells become less effective because of the build up of damaged DNA. Our study identifies a key source of this DNA damage and defines two protective mechanisms that stem cells use to counteract this threat. Last year we published a paper showing that without this two-tier protection, alcohol breakdown products are extremely toxic to the blood. We now identify exactly where this DNA damage is occurring, which is important because it means that alcohol doesn’t just kill off healthy circulating cells, it gradually destroys the blood cell factory. Once these blood stem cells are damaged they may give rise to leukaemias and when they are gone they cannot be replaced, resulting in bone marrow failure,” Dr KJ Patel, who is the primary investigator.

“The findings may be particularly significant for a vast number of people from Asian countries such as China, where up to a third of the population are deficient in the ALDH2 enzyme. Alcohol consumption in these individuals could overload their FA DNA repair kit causing irreversible damage to their blood stem cells. The long-term consequences of this could be bone marrow dysfunction and the emergence of blood cancers,” Patel added.

“This study provides much sought-after explanation of the biology underpinning the devastating childhood disease Fanconi anemia. In future this work may underpin new treatments for this genetic disease, which currently is associated with a very poor prognosis. It also helps to inform large numbers of the global population, who are deficient in the ALDH2 enzyme, that drinking alcohol may be inflicting invisible damage on their DNA,” commented Sir Hugh Pelham, director of the MRC Laboratory of Molecular Biology.

2012-08-28T17:39:57+00:00August 28th, 2012|Adult Stem Cells, News, Stem Cell Research|

Endometrial Stem Cells Yeild Postive Clinical Trial Results for Heart Disease

More progress reported on the treatment of heart disease with endometrial stem cells. Neil Riordan, PhD is one of the early pioneers of endometrial stem cell technology. Dr. Riordan is also the Founder and President of the Stem Cell Institute in Panama City, Panama.

Positive Two-Month Data From RECOVER-ERC Congestive Heart Failure Trial

SAN DIEGO, CA–(Marketwire – Jun 4, 2012) – Medistem Inc. (PINKSHEETS: MEDS) announced today positive safety data from the first 5 patients enrolled in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The clinical trial uses the company’s “Universal Donor” Endometrial Regenerative Cells (ERC) to treat Congestive Heart Failure (CHF).

According to the study design, after 5 patients enter the trial, they must be observed for a two month time period before additional patients are allowed to enter the study. Patient data was analyzed by the study’s independent Data Safety Monitoring Board (DSMB), which concluded that based on lack of adverse effects, the study be allowed to continue recruitment.

“Medistem is developing a treatment for CHF that uses a 30-minute catheter-based procedure to administer the ERC stem cell into the patients’ hearts. The achievement of 2 month patient follow-up with no adverse events is a strong signal for us that our new approach to this terrible condition is feasible,” said Thomas Ichim, CEO of Medistem.

The RECOVER-ERC trial will treat a total of 60 patients with end-stage heart failure with three concentrations of ERC stem cells or placebo. The clinical trial is being conducted by Dr. Leo Bockeria, Chairman of the Backulev Centre for Cardiovascular Surgery, in collaboration with Dr. Amit Patel, Director of Clinical Regenerative Medicine at University of Utah.

“As a professional drug developer, I am very optimistic of a stem cell product that can be used as a drug. The ERC stem cell can be stored frozen indefinitely, does not need matching with donors, and can be injected in a simple 30-minute procedure into the heart,” said Dr. Sergey Sablin, Vice President of Medistem and co-founder of the multi-billion dollar NASDAQ company Medivation.

Currently patients with end-stage heart failure, such as the ones enrolled in the RECOVER-ERC study, have no option except for heart transplantation, which is limited by side effects and lack of donors. In contrast to other stem cells, ERC can be manufactured inexpensively, do not require tissue matching, and can be administered in a minimally-invasive manner. Animal experiments suggest ERC are more potent than other stem cell sources at restoring heart function. The FDA has approved a clinical trial of ERC in treatment of critical limb ischemia in the USA.

About Medistem Inc.
Medistem Inc. is a biotechnology company developing technologies related to adult stem cell extraction, manipulation, and use for treating inflammatory and degenerative diseases. The company’s lead product, the endometrial regenerative cell (ERC), is a “universal donor” stem cell being developed for critical limb ischemia and heart failure. A publication describing the support for use of ERC for this condition may be found at http://www.translational-medicine.com/content/pdf/1479-5876-6-45.pdf.

Cautionary Statement
This press release does not constitute an offer to sell or a solicitation of an offer to buy any of our securities. This press release may contain certain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Future events and actual results could differ materially from those set forth in, contemplated by, or underlying the forward-looking information. Factors which may cause actual results to differ from our forward-looking statements are discussed in our Form 10-K for the year ended December 31, 2007 as filed with the Securities and Exchange Commission.

Medistem Contact:

Thomas Ichim
Chief Executive Officer
Medistem Inc.
9255 Towne Centre Drive
Suite 450
San Diego
CA 92122
858 349 3617
858 642 0027
www.medisteminc.com
twitter: @thomasichim

2012-06-06T17:50:59+00:00June 6th, 2012|Adult Stem Cells, Heart Disease, News, Stem Cell Research|

Adult Stem Cell Therapy Successfully Treats Spinal Cord Injury

An interesting spinal cord injury study was published last week. The Turkish researchers tested two types of stem cells on spinal cord injured mice. The two cell types were native bone marrow cells and cultured repair stem cells called Mesenchymal stem cells. Native bone marrow cells contain bone marrow forming stem cells as well as a small number of Mesenchymal stem cells.

After injuring the spinal cords, the stem cells were implanted at the site of the injury. The control mice that received no cells had no improvement in neural activity. The mice that received both cell types had improved neural activity. The cultured Mesenchymal stem cell group improved significantly more than the native bone marrow stem cell group.

Stem Cell Rev. 2012 May 3. [Epub ahead of print]
Stem Cell Therapy in Spinal Cord Injury: In Vivo and Postmortem Tracking of Bone Marrow Mononuclear or Mesenchymal Stem Cells.
Ozdemir M, Attar A, Kuzu I, Ayten M, Ozgencil E, Bozkurt M, Dalva K, Uckan D, Kılıc E, Sancak T, Kanpolat Y, Beksac M.

Source
School of Medicine, Department of Neurosurgery, Pamukkale University, 20070, Kinikli, Denizli, Turkey, drmevci@hotmail.com.

Abstract
OBJECTIVE:
The aim of this study was to address the question of whether bone marrow-originated mononuclear cells (MNC) or mesenchymal stem cells (MSC) induce neural regeneration when implanted intraspinally.

MATERIALS AND METHODS:
The study design included 4 groups of mice: Group 1, non-traumatized control group; Groups 2, 3 and 4 spinal cord traumatized mice with 1 g force Tator clips, which received intralesionally either no cellular implants (Group 2), luciferase (Luc) (+) MNC (Group 3) or MSC (Group 4) obtained from CMV-Luc or beta-actin Luc donor transgenic mice. Following the surgery until decapitation, periodical radioluminescence imaging (RLI) and Basso Mouse Scale (BMS) evaluations was performed to monitor neural activity. Postmortem immunohistochemical techniques were used to analyze the fate of donor type implanted cells.

RESULTS:
All mice of Groups 3 and 4 showed various degrees of improvement in the BMS scores, whereas there was no change in Groups 1 and 2. The functional improvement was significantly better in Group 4 compared to Group 3 (18 vs 8, p = 0.002). The immunohistochemical staining demonstrated GFP(+)Luc(+) neuronal/glial cells that were also positive with one or more of these markers: nestin, myelin associated glycoprotein, microtubule associated protein or myelin oligodendrocyte specific protein, which is considered as indicator of donor type neuronal regeneration. Frequency of donor type neuronal cells; Luc + signals and median BMS scores were observed 48-64 % and 68-72 %; 44-80 %; 8 and 18 within Groups III and IV respectively.

DISCUSSION:
MSCs were more effective than MNC in obtaining neuronal recovery. Substantial but incomplete functional improvement was associated with donor type in vivo imaging signals more frequently than the number of neuronal cells expressing donor markers in spinal cord sections in vitro. Our results are in favor of functional recovery arising from both donor MSC and MNCs, contributing to direct neuronal regeneration and additional indirect mechanisms.

How Nasal Stem Cells Might Prevent Childhood Deafness

Medical News Today

Sensorineural hearing loss is a type of deafness that generally begins in childhood, a condition that results from hearing cells in the cochlea losing their function. The hearing loss that occurs can often slow the development of the child and possibly cause speech and language problems to develop.

Fortunately, Australian scientists have discovered a possible way to restore or reverse this condition. It has been shown in mice that injecting nasal stem cells into the inner ear can effectively reverse the condition during early onset hearing loss. The stem cells release signaling factors that help preserve the function of the cochlear cells.

“We are exploring the potential of stem cells to prevent or restore hearing loss in people,” said project leader Dr Sharon Oleskevich. “We are encouraged by our initial findings, because all the mice injected with stem cells showed improved hearing in comparison with those given a sham injection. Roughly half of the mice did very well indeed, although it is important to note that hearing was not completely restored to normal hearing levels.”

2012-02-13T20:28:23+00:00February 13th, 2012|Clinical Trials, News, Stem Cell Research|

Medistem Begins Phase II Clinical Trial for Heart Failure

Medistem Inc announced today treatment of 3 heart failure patients in the Non-Revascularizable IschEmic Cardiomyopathy treated with Retrograde COronary Sinus Venous DElivery of Cell TheRapy (RECOVER-ERC) trial. The trial is aimed at assessing safety and efficacy of the company’s Endometrial Regenerative Cell (ERC) stem cell product in 60 heart failure patients who have no available treatment options. The cells were discovered by Dr. Neil Riordan and the team at Medistem. The “Universal Donor” adult stem cells will be administered using a novel catheter-based retrograde administration methodology that directly implants cells in a simple, 30 minute, procedure.

“We are honored to have had the opportunity to present at the prestigious Cardiovascular Stem Cell Research Symposium, alongside companies such as Athersys, Aastrom, Pluristem, Cardio3, Cytori, and Mesoblast,” stated Thomas Ichim, CEO of Medistem. “The RECOVER-ERC trial is the first trial combining a novel stem cell, with a novel administration procedure. Today cardiac administration of stem cells is relatively invasive and can only be performed at specialized institutions, we feel the retrograde procedure will circumvent this hurdle.”

Medistem has been focusing on the endometrium because this is a unique tissue in that it undergoes approximately 500 cycles of highly vascularized tissue growth and regression within a tightly controlled manner in the lifetime of the average female. One of the first series of data describing stem cells in the endometrium came from Prianishnikov in 1978 who reported that three types of stem cells exist: estradiol-sensitive cells, estradiol- and progesterone-sensitive cells and progesterone-sensitive cells.

Interestingly, a study in 1982 demonstrated that cells in the endometrium destined to generate the decidual portion of the placenta are bone marrow derived, which prompted the speculation of a stem cell like cell in the endometrium. Further hinting at the possibility of stem cells in the endometrium were studies demonstrating expression of telomerase in endometrial tissue collected during the proliferative phase. One of the first reports of cloned stem cells from the endometrium was by Gargett’s group who identified clonogenic cells capable of generating stromal and epithelial cell colonies, however no differentiation into other tissues was reported. The phenotype of these cells was found to be CD90 positive and CD146 positive. The cells isolated by this group appear to be related to maintaining structural aspects of the endometrium but to date have not demonstrated therapeutic potential. In 2007, Meng et al, used the process of cloning rapidly proliferating adherence cells derived from menstrual blood and generated a homogenous cell population expressing CD9, CD29, CD41a, CD44, CD59, CD73, CD90, and CD105 and lacking CD14, CD34, CD45 and STRO-1 expression. Shortly after, Patel’s group reported a population of cells isolated using c-kit selection of menstrual blood mononuclear cells. The cells had a similar phenotype, proliferative capacity, and ability to be expanded for over 68 doublings without induction of karyotypic abnormalities. Interestingly both groups found expression of the pluripotency gene OCT-4 but not NANOG. More recent investigations have confirmed these initial findings. For example, Park et al demonstrated that endometrial cells are significantly more potent originating sources for dedifferentiation into inducible pluripotent cells as compared to other cell populations. Specifically, human endometrial cells displayed accelerated expression of endogenous NANOG and OCT4 during reprogramming compared with neonatal skin fibroblasts. Additionally, the reprogramming resulted in an average colony-forming iPS efficiency of 0.49 ± 0.10%, with a range from 0.31-0.66%, compared with the neonatal skin fibroblasts, resulting in an average efficiency of 0.03 ± 0.00% per transduction, with a range from 0.02-0.03%. Suggesting pluripotency within the endometrium compartment, another study demonstrated that purification of side population (eg rhodamine effluxing) cells from the endometrium results in a population of cells expressing transdifferentiation potential with a genetic signature similar to other types of somatic stem cells.

Given the possibility of ERC playing a key role in angiogenesis, Murphy et al utilized an aggressive hindlimb ischemia model combined with nerve excision in order to generate a model of limb ischemia resulting in limb loss. ERC administration was capable of reducing limb loss in all treated animals, whereas control animals suffered necrosis. In the same study, ERC were demonstrated to inhibit ongoing mixed lymphocyte reaction, stimulate production of the anti-inflammatory cytokine IL-4 and inhibit production of IFN-g and TNF-alpha. It is important to note that the animal model involved administration of human ERC into immunocompetent BALB/c mice. The relationship between angiogenesis and post myocardial infarct healing is well-known. Given previous work by Umezawa’s group demonstrating myocytic differentiation of ERC-like cells, administration of ERC into a model of post infarct cardiac injury was performed. Recovery was compared to bone marrow MSC. A superior rate of post-infarct recovery of ejection fraction, as well as reduction in fibrosis was observed with the ERC-like cells. Furthermore, it was demonstrated that the cells were capable of functionally integrating with existing cardiomyocytes and exerted effects through direct differentiation. The investigators also demonstrated in vitro generation of cardiomyocyte cells that had functional properties.

The RECOVER-ERC TRIAL that has begun will recruit 60 patients with congestive heart failure, which will be randomized into 3 groups of 20 patients each. Group 1 will receive 50 million ERC, Group 2 will receive 100 million and Group 3 will receive 200 million. Cells will be administered via catheter-based retrograde administration into the coronary sinus, a 30 minute procedure developed by Dr. Amit Patel’s Team. Each group will comprise of 15 patients receiving cells and 5 patients receiving placebo. Efficacy endpoints include ECHO and MRI analysis, which will be conducted at 6 months after treatment. The trial design is similar to the recent Mesoblast Phase II cardiac study, in order to enable comparison of efficacy.

2012-01-30T18:42:22+00:00January 30th, 2012|Adult Stem Cells, Heart Disease, News, Stem Cell Research|

Mechanism by Which Injured Tissue “Tells” Stem Cells to Leave Bone Marrow

Urao et al. Stem Cells. 2012 Jan 30.

In addition to the established role of bone marrow derived stem cells in producing blood cells, an interesting aspect of these stem cells is to assist/accelerate tissue healing after injury. Perhaps the most studied example of this is in the situation of myocardial infarction (heart attack), in which damaged heart muscle sends out signals to the bone marrow, which cause selective homing of bone marrow stem cells into the damaged heart tissue. This is believed to occur via activation of the transcription factor HIF-1 alpha due to lack of oxygen in the tissue. HIF-1 alpha binds to DNA and induces activation of a variety of genes that are involved in angiogenesis such as VEGF, FGF-2, and IL-20. Additionally, HIF-1 alpha stimulates production of the chemokine stromal derived factor (SDF)-1, which attracts bone marrow stem cells by binding to the CXCR4 receptor. The importance of SDF-1 in terms of bone marrow stem cell migration is exemplified in the situation of bone marrow transplantation. When a transplant is performed the bone marrow recipient is administered the donor stem cells intravenously and not intraosteolly (inside the bone). The reason for this is because the bone marrow itself constantly produces SDF-1 which attracts injected stem cells that express CXCR4.

During infarction, the concentration of SDF-1 produced by the damaged heart muscle is higher than the concentration of SDF-1 in the bone marrow, and as a result, stem cells from the bone marrow leave the bones, enter circulation, and home to the heart. Similar examples are found in the situation of stroke. In stroke patients, not only do bone marrow stem cells enter circulation after the stroke, but it has been reported that patients with higher number of stem cells in circulation actually have better outcomes.

The possibility of chemically “mobilizing” bone marrow stem cells into circulation is very attractive. On the one hand, it would be conceptually possible to augment the extent of regeneration by increasing the number of circulating stem cells, and on the other hand, it may be possible to perform “bone marrow transplantation” without the painful procedure of drilling holes through the bones of the donor. In fact, the second possibility is actually part of clinical practice. Doctors use the drug G-CSF, otherwise known as Neupogen, to cause donor migration of bone marrow stem cells into circulation, which are then harvested by leukopheresis, so that bone marrow puncture is not needed. The first possibility, the therapeutic use of bone marrow mobilization has resulted in mixed data. Some groups have demonstrated significant improvement in heart attack patients treated with G-CSF, whereas others have reported no benefit. Recently a new way of mobilizing stem cells has been approved by the FDA: a small molecule drug called Mozobil which blocks the interaction between SDF-1 and CXCR4. This drug was developed by the company Anormed and sold to Genzyme, a major Biopharmaceutical company.

In a recent paper, the role of oxidative stress was investigated in the animal model of critical limb ischemia. Critical limb ischemia is a condition in which patients experience poor circulation in the lower extremities, usually as a result of advanced peripheral artery disease. To replicate this condition in animals, the femoral artery which feeds the leg is ligated, and perfusion of the leg is measured, usually with Doppler ultrasound. In the mouse model there is a gradual recovery of blood flow as a result of spontaneous angiogenesis (new blood vessel formation). It is believed that bone marrow stem cells are involved in the formation of these new blood vessels.

While it is known that ischemia in the leg muscle is associated with recruitment of stem cells by production of SDF-1, little is known involving the changes that occur in the bone marrow as a result of ischemia in the leg.

Scientists demonstrated that after mice are subjected to hindlimb ischemia, there is a major increase in the production of free radicals in the bone marrow, specifically in the endosteal and central region of the bone marrow. Interestingly, these free radicals appear to be made by the enzyme Nox2 because mice lacking this enzyme do not have free radicals produced in the bone marrow as a result of leg ischemia. The enzyme appears to be expressed mainly in the Gr-1(+) myeloid suppressor cells that are found in the bone marrow. Free radicals were found to be associated with expression of HIF-1 alpha, implying occurrence of localized hypoxia. As can be expected, HIF-1 alpha expression was also found to associate with production of the angiogenic cytokine VEGF. It appeared that bone marrow VEGF expression was associated with expansion of bone marrow Lin(-) progenitor cell survival and expansion, leading to their mobilization into systemic circulation. It was furthermore demonstrated that ischemia of the leg increased expression of the proteolytic enzymes MT1-MMP and MMP-9 activity in the bone marrow, which did not occur in mice lacking Nox2.

The identification of NOX2 as being critical in the mobilization of bone marrow stem cells in response to ischemia suggests that antioxidants may actually modulate the extent of bone marrow stem cell mobilization. Conversely, if one believes the concept proposed, then oxidative stress (at least in a short term setting) would be beneficial towards mobilization. This is supported by studies showing that hyperbaric oxygen induces transient mobilization of bone marrow stem cells. For example Dhar et al. published (Equine peripheral blood-derived mesenchymal stem cells: Isolation, identification, trilineage differentiation and effect of hyperbaric oxygen treatment. Equine Vet J. 2012 Feb 15) that hyperbaric oxygen treatment in horses increased yield of mesenchymal stem cells collected from peripheral blood. Thom et al (Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy. Wound Repair Regen. 2011 Mar-Apr;19(2):149-61) reported 2-fold increases in hematopoietic stem cells (identified by CD34 expression) in diabetic patients who received hyperbaric oxygen. This study also demonstrated that the CD34 cells that were found in circulation contained high expression of HIF-1 alpha, implying that they may possess angiogenic activity. An interesting experiment would have been if they removed the cells and assessed in vitro angiogenic activity. Indeed it is known that in patients with diabetes the CD34 cells possess a reduced angiogenic activity. If hyperbaric oxygen stimulates this angiogenic activity, it may be a relatively non-invasive method of augmenting the “rejuvenation” potential of the patient’s own stem cells. Another interesting finding of the study was that hyperbaric oxygen was associated with an increase in nitric oxide production by platelets. Since nitric oxide can act as an anticoagulant, this may be another benefit of using hyperbaric oxygen.

One important question is the potency of the stem cell mobilization induced by hyperbaric oxygen. Specifically, while it is nice that an increase in CD34 cells is observed, what activity do these cells actually have ? An earlier study by Thom et al (Stem Cell Mobilization by Hyperbaric Oxygen. Am J Physiol Heart Circ Physiol. 2006 Apr;290(4):H1378-86) demonstrated that the colony-forming ability of the mobilized cells was actually 16-20 fold higher compared to controls. Colony-forming ability is an assessment of the stem cells to generate new cells in vitro.

Thus the paper we discussed sheds some interesting light on the connection between “oxidative medicine” and stem cell biology. Obviously more studies are needed before specific medical recommendations can be made, however, given the large number of patients being treated with alternative medicine techniques such as hyperbaric oxygen, one must ask whether other treatments of this nature also affect stem cells. For example, what about ozone therapy? Or intravenous ascorbic acid?

2012-01-30T18:40:24+00:00January 30th, 2012|Adult Stem Cells, News, Stem Cell Research|

Stem cells secrete factors that promote muscle growth after exercise

Stem cells that aid in healing disease and injury in skeletal muscle have been found inside muscles in greater numbers after exercise, according to a new animal study at the University of Illinois.

Just one exercise session increases the number of muscle-derived mesenchymal stem cells (mMSCs) in mice, according to Beckman Institute researcher Marni Boppart. Dr. Bopart is an assistant professor of kinesiology and community health at the University of Illinois.

mMSCs can differentiate (change) into many different cell types and are found throughout the body. For the first time, this study also showed that they also facilitate tissue healing indirectly.

Bopart said, “What we’ve been able to show in this paper and our current work is that mMSCs are not directly contributing to muscle growth, but do in fact secrete a variety of different factors that positively impact muscle growth.”

Bopart believes that these secreted factors, which specifically respond to mechanical strain are an important step toward treatments that can prevent muscle loss that occurs with aging.

This work was reported in the journal PlosOne.

2012-01-20T18:50:22+00:00January 20th, 2012|Adult Stem Cells, Muscular Dystrophy, News, Stem Cell Research|