Bone Marrow Therapies
Bone Marrow Therapies
TREATING NEUROLOGIC ISSUES WITH STEM CELL-RICH BONE MARROW
ASPIRATE CONCENTRATE (BMAC): SAFE, EFFECTIVE AND LEGAL
David A. Steenblock, MS, DO
Director, David A. Steenblock, DO, Inc. and President, Steenblock Research Institute (San Clemente, California USA)
During the past decade or so podiatric physicians and orthopedic surgeons have found stem cell rich bone marrow aspirate concentrate (BMAC) an excellent clinical tool for facilitating healing and restoration in patients with osteoarthritis (mainly knees), osteoradionecrosis, cartilage loss in various joints. bony non-unions, chondraldefects, and much more. The use of BMAC including research using it expanded somewhat recently including a 2011 Tufts Medical Center multicenter, prospective, randomized, double-blind, placebo-controlled study for “no option” critical limb ischemia (CLI) in which patients who got BMAC experienced improvement in measures such as amputations done, pain, quality of life, Rutherford classification, and ABI (ankle brachial index) compared with controls1.
However, little discussion or research exists with regard to the clinical use of BMAC to remediate or cure neurologic diseases and conditions, especially intractable and terminal ones. On October 21 of this year (2015) I did a search of the US government clinical trials database at http://clinicaltrials.gov/ using “bone marrow aspirate concentrate” as a search term which produced seven studies that are actively recruiting patients. Most of these concern BMAC use for specific orthopedic and musculoskeletal issues. None dealt with neurologic diseases or conditions.Bottom of Form
This is perplexing to me as I have been using BMAC to treat patients with neurologic and other (largely non-orthopedic) issues since 2005. In fact, I have performed over 2000 BMAC treatments to-date, with clinical outcomes being uniformly better that what was true prior to their introduction. The sole exception was older sedentary patients whose marrow typically contains less robust stem cells, although this was remedied when I began doing using Neupogen® to purge these senescent cells, a process that triggered their replacement with more vigorous stem cells (More on this further down).
BACKGROUND: MY JOURNEY INTO THE WORLD OF STEM CELL MEDICINE
My introduction to bone marrow stem cells took place in 1969 during my tenure as a young physician extern in the Department of Hematology & Oncology at the University of Washington. At this time I got the impression that stem cells were pretty much unknown among other doctors and that my UW associates and I were going to launch a new age of regenerative medicine using them. This was not at all presumptive as the particular program I was part of was run by Edward Donnall (“Don”) Thomas, MD, a man whose extraordinary career culminated in his being awarded the 1990 Nobel Prize in Physiology or Medicine along with another physician, Joseph E. Murray, for the development of cell and organ transplantation. It was, in fact, Dr. Thomas who developed bone marrow transplantation as a way to treat leukemia. Ultimately, he and his team did over 4,000 bone marrow transplants2.
Following some specialized training in pathology and work as a pathologist, I gravitated into what was then called Wholistic medicine (Later complementary-alternative medicine or CAM and now integrative medicine). Like many in-the-know CAM/IM doctors I ran across the pioneering work of Paul Niehans, MD and his colleagues in Europe who had reported great clinical responses in patients given injections of fresh embryonic cells from animals, typically lambs (“Live Cell Therapy”). These cells were not rejected or linked to adverse effects or side effects.
During the early 1990s I crossed paths with a Mexican orthopedic surgeon who had been using blue shark embryonic tissues to coax turnarounds in people with spinal cord injuries. We began collaborating in this work from roughly 1991 to 2001, but switched to the use of pure (human) umbilical cord stem cells in 2003 (Everything being done in Mexico with authorization from the Mexican government).
At this time I set up a nonprofit research institute bearing my name (Steenblock Research Institute – SRI) in southern California for the purpose, in part, of helping educate people on the clinical work going on in Mexico and then tracking those who had umbilical cord stem cell treatments there.
In time my SRI staff and I had accumulated response and outcome data on over 1000 patients treated with umbilical cord stem cells in Mexico. Then, with my participation, SRI and the medical team in Mexico carried out an open label pilot study in Mexico during 2004 in which eight children with cerebral palsy were each given a subcutaneous injection of 1.5 million CD34+/AC133 umbilical cord stem cells (near their belly buttons). The majority of the children experienced statistically significant improvements in a number of bodily functions. One 5 year old boy went on to experience a partial resolution of cortical blindness due to optic nerve hypoplasia3.
Armed with this body of sometimes remarkable clinical successes, I coauthored a book containing many case histories which came out in 2006 and was titled “Umbilical Cord Stem Cell Therapy: The Gift of Healing from Newborns” (Basic Health Publishing).
But as impressive as umbilical cord stem cell use was, I pondered whether stem cells from a patient’s own fat and bone marrow (autologous stem cells) would be as effective if not more so. It made sense to me that they would do as well or better than cord derived stem cells because they are autologous and hence would not have any chance of provoking a “foreign” reaction when administered to patients.
Fat tissue contains lots of mesenchymal stem cells but its liposuction extraction can be more “body traumatic” in more so than bone marrow tissue harvesting from the hip. In addition fat stem cells require being separated from the person’s fat by the use of an enzyme and according to the FDA this makes fat stem cells into a “non-approved drug”. These facts and my bone marrow transplant work at the University of Washington leant me to favor working with bone marrow stem cells. The biggest hurdle at this point-in-time (2005) was a regulatory one: The FDA had declared that processing bone marrow stem cells beyond a certain point for use in patients constituted a new drug and by virtue of this required filing an IND (new drug application) with them and then going through the formidable, costly new drug approval process. But what about taking bone marrow tissue, spinning it down in a centrifuge, siphoning off the cell rich top layer (buffy coat) and then giving this to patients?
To find out if what I was thinking was “FDA kosher” I had my FDA regulations savvy lawyer, Richard Jaffe (J.D., Columbia University School of Law), ask the powers-that-be at the agency. A few weeks later an email was sent to Mr. Jaffe which stated that the use of “minimally manipulated” bone marrow was not regulated by the FDA and fell under the practice of medicine!
With this bit of good news in-hand I began working with bone marrow aspirate concentrate or BMAC starting in the spring of 2005. In the ensuing years I have performed over 2000 BMAC treatments, many done to help people with intractable and even terminal neurologic conditions e.g., cerebral palsy, traumatic brain injury (TBI), chronic stroke, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s disease), etc.
BACKGROUND ON EMBRYONIC & ADULT STEM CELLS (Especially bone marrow)
By the late 1990s the world of biomedicine was abuzz over the work being done with embryonic stem cells which seem to herald the age of regenerative medicine. However, as ethical objections were raised over using embryonic stem cells and gained momentum, and various studies were published that demonstrated these stem cells produced teratomas in lab animals, many scientists and physicians shifted their focus to adult (nonembryonic) stem cells.
So what exactly distinguishes embryonic from other stem cells? In-a-word, plasticity or what is called developmental versatility. Embryonic stem cells, for instance, are pluripotent which means they have the potential to become (differentiate) into any of the three germ layers (endoderm, mesoderm, ectoderm) that give rise to all the organs and tissues that make all of us up. By virtue of this embryonic stem cells become any bodily cell type, e.g., skin cells, nerve cells, heart cells, etc., in both fetuses and what follows after birth (Baby through adult).
When nestled in its native biological environment (early cell collective, first as an embryo and then fetus), embryonic stem cells receive a series of carefully orchestrated series of biochemical signals from surrounding tissues that tells them to follow specific developmental pathways in precise ways (A baby results). When the amounts of these biochemical signals are too low or high or missing altogether, create signaling conflicts, or make their appearance in the wrong order, something that has happened when embryonic stem cells were placed in the tissues or organs in lab animals, they can remain undifferentiated, differentiate into a cell type that differs from the tissue they are engrafted in, or even form a teratoma.
Adult stem cells, on the other hand, arise after early stage embryonic development and are found in all our organs, plus adipose, dental pulp and many other tissues. They are more restricted in terms of the types of bodily cell types they can become. This makes good biological sense as most of these stem cells never leave the tissue or organ they are part of and basically serve to replace cells that die off or are injured or become diseased. These stem cells thus serve as the body’s natural R & R (repair and regeneration) kit.
In addition, stem cells exist in umbilical cord blood & the gelatinous Wharton’s Jelly that envelopes umbilical cord blood vessels, as well as the amniotic sac and amniotic fluid, and placenta. These stem cells are more biologically plastic or developmentally versatile than adult stem cells taken from fully formed tissues and organs, yet unlike embryonic stem cells do not form teratomas.
The adult stem cells in most organs and tissues are a mix of multipotent, oligopotent and unipotent stem cells. These terms refer to their developmental plasticity or versatility. For instance, multipotent stem cells can differentiate into (become) a number of somatic (body) cell types, but only into those of a closely related family of cells. Oligopotent stem cells generally can differentiate into only a few cell types such as lymphoid or myeloid cells, while unipotent cells give rise to one somatic (body) cell type, their own, though they possess the property of self-renewal (Something which sets them apart from non-stem cells).
Interestingly, bone marrow tissue and umbilical cord blood is rich in multipotent stem cells including mesenchymal stem cells and also a very small number of pluripotent marker-rich stem cells called small embryonic-like stem cells (VSELs). So why don’t these VSELs readily form teratomas when placed in animals or people? This appears to be linked to their exposure to growth factors and possibly other powerful biological molecules in the more developmentally advanced tissues they come from that are absent in embryos, which leaves them less likely to form teratomas.
Umbilical cord stem cells cannot be used in the USA outside of approved lab & clinical research and to treat a narrow range of conditions approved by the FDA. Bone marrow tissue can be harvested and used to treat patients so long as it is not processed beyond a certain point (The FDA requires that it be “minimally manipulated”. Otherwise, it constitutes a new drug and has to go through the multi-step drug approval process). In addition to stem cells, tissue obtained from the hip (iliac crest) contains:
- Endothelial progenitor cells (EPCs) which stimulate angiogenesis or new blood vessel formation, as well as secrete powerful proteins such as BMP-2 and BMP-6. EPSs also stimulate other cells to churn out BMP-2.
- Granulocytes which are white blood cells that release vascular endothelial growth factor (VEGF) that promotes vasculogenesis and angiogenesis. VEGF also stimulates neurogenesis in vitro and in vivohttp://www.pnas.org/content/99/18/11946.full.
- Lymphocytes which are one of 3 white blood cell types that, among other things, support the proliferation and migration of EPCs. ‘
- Platelets which play a role in cell-to-cell adhesion by secreting various adhesion and growth factors such as SDF-1 facilitates hematopoietic stem cell mobilization and migration, and acts as a homing factor or biologic beacon for stem cells. SDF-1 also modulates inflammation which is a player in many acute and chronic diseases.
Bone marrow stem cells also express numerous growth factors (plus a chemokine or cell signaling compound), typically upon engraftment, including:
- Bone morphogenic proteins 1, 2, 3, 4, 6, 7, 8B, R1A, and PR2. These have various effects including being vital to cartilage and bone development plus fracture repair. BMP7 is involved in renal development and repair.
- Transforming growth factors (TGFs) TGFA, TGFB1, TGFB2 and TGFB3: TGFs are a family of structurally related proteins that control proliferation, differentiation and other functions in many cell types.
- Nerve Growth Factor (Bone marrow mesenchymal stem cells): NGF is a small protein that plays a vital role in the differentiation, growth, maintenance, and survival of sensory and sympathetic neurons. It also functions as a signaling molecule.
Source for growth factors formation above: “Growth factors and gene expression of stem cells: bone marrow compared with peripheral blood” http://www.ncbi.nlm.nih.gov/pubmed/20523179
- Hepatocyte growth factor (Bone marrow Mesenchymal stem cells)4 : HGF targets and acts primarily upon epithelial cells, endothelial cells and also hematopoietic progenitor cells. It has been shown to play a major role in wound healing and adult organ regeneration.
- Insulin-like growth factor-15 : IGF-1 is one of the most potent natural activators of a specific signaling pathway (AKT) that both stimulates cell growth and proliferation and inhibits apoptosis (programmed cell death). In addition, IGF-1 is a primary mediator of the effects of growth hormone (GH).
THE USE OF BMAC: PLUGGING INTO AND AUGMENTING A NATURAL HEALING MECHANISM
One of the arguments put forward by some critics of my use of bone marrow aspirate concentrate (BMAC) to remediate and heal various neurologic diseases and conditions is their contention that bone marrow stem cells stem cells do not naturally play this role in the human body. This, however, is specious reasoning as studies have been done since 2006 (when I began using BMAC on neurologic cases) demonstrating that neuroinflammation stimulates mobilization of bone marrow stem cells, some of which make their way through the blood-brain barrier to the inflammation site6.7. This bodily response likely reflects a natural mechanism for dealing with injury or disease. As such, my clinical use of BMAC amounts to tapping into and augmenting a natural process.
The clinical responses I have seen and charted since commencing use of BMAC in 2005 certainly lend credence to this contention. I have, in fact, documented impressive and sometimes remarkable turnarounds in people with ALS, chronic stroke, cerebral palsy, traumatic brain injury (TBI), Parkinson’s disease, and other conditions. Click to see a sampling of videotaped patient reports.
Nature, however, did impose challenges that I had to overcome. For instance, by 2010 it was clear that the use of BMAC in patients under the age of forty produced uniformly good-to-impressive clinical improvements, while virtually the opposite was true in most patients over forty. Of course, older patients typically present with more chronic medical issues than younger ones. But this alone, I found, was not sufficient to account for all less than stellar clinical responses. The culprit? An age-related shift in the proportion stem cell rich red marrow to yellow, fat-rich and stem cell poor marrow tissue in the bones of older and especially sedentary older patients! In short, older patients whose marrow was “stem cell poor” got less auspicious results than those with marrow populated by far more vigorous stem cells.
Thankfully, I noticed that the marrow of older patients who exercised daily by running or walking, or who spent a great deal of time hiking in high mountains or regularly donated blood, had healthier, more abundant red bone marrow than their less active contemporaries. This was even more pronounced when it came to older, less active folks with emphysema, Parkinson’s disease, dementia, and many other chronic diseases and medical conditions.
Since older patients who hiked at higher altitudes had more red marrow in their bones, I surmised that simulating this by use of Intermittent Hypoxia Therapy (IHT) in less active older patients should coax the bone marrow to replace yellow, stem cell poor marrow with red, stem cell-rich marrow. I then had some of my older sedentary patients do IHT (in my clinic) and saw the anticipated “color shift” (Pre-IHT and post-IHT bone marrow samples were taken for comparison purposes).
As I thought about other ways to effect this “color shift”, I recalled published studies which revealed the fact that when large numbers of stem cells were mobilized from bone marrow using specific drugs like granulocyte colony-stimulating factor, it would respond by producing replacement stem cells that were more active (vigorous) than those had been mobilized or “purged”. I then searched the PubMed and other data bases which brought up many papers by David T. Scadden§ and his colleagues at Harvard (dating from roughly 2008 on) that supported the “when the old are purged , new & healthier cells are produced” thesis and included confirmatory support from various lab animal studies8. However, I could not locate any studies indicating that bone marrow stem cell mobilization had been used in people for the purpose of determining whether the flushed out or vacated stem cell niches would wind up being filled with new, more pristine and thus more vigorous stem cells. This fact spurred me to try injections of FDA approved colony stimulating factors such as Neupogen® to mobilize bone marrow stem cells, particularly in older, sedentary people. And, not surprisingly, pre- and post- Neupogen® purge bone marrow samples clearly showed that the mobilization regimen had prodded the bone marrow tissue to produce abundant new, more vibrant stem cells.
In time and with additional in-office experimentation, I discovered that the greatest number of new stem cells would be produced when Neupogen® was given for five (5) consecutive days by injection followed by a two week wait. This was independently verified by the stem cell biologist at SRI. Indeed, he found upwards of ten (10) times more healthy stem cells in the post-purge samples of those who did the aforementioned injection regimen.
And as you would expect, older patients who did the Neupogen® purge and then had bone marrow harvested and given back to them as a BMAC treatment had demonstrably better clinical outcomes than age-matched patients with similar medical problems, e.g., chronic stroke, ALS (Lou Gehrig’s disease), multiple sclerosis, Alzheimer’s and other dementias, or traumatic brain injury, who’d not had the Neupogen® purge.
These clinical successes and the fact the BMAC treatments had proven quite safe, led me to begin treating young people with neurological problems such as cerebral palsy, Huntington’s disease and autism. I also did BMAC treatments on people with non-neurological issues including people with joint, eye, cardiac, kidney, respiratory and gastrointestinal diseases and conditions. Most enjoyed improvements “worth writing home about” (to put it mildly).
HOW DOES BMAC AFFECT HEALING AND RESTORATION?
The clinical successes which I and others have seen in patients treated with BMAC naturally raises the question of how they pull this off. Do the stem cells in the harvested bone marrow differentiate (become) the cell types of the tissue they engraft in or do they become cell types that support or encourage healing and restoration? Or do they instead produce and secrete substances that have a paracrine (cell-to-cell signaling) effect which promotes healing and restoration? Or is it both?
The best answer at this point-in-time is that both are involved. This contention is supported by various studies including these:
In 2002 University of Minnesota scientists induced strokes in lab animals (rats) and then a week later grafted pure human mesenchymal stem cells (MSCs) into the cortex surrounding the area of stroke damage (infarction). Tissue analyses showed that the transplanted MSCs had biomarkers (biological signs or characteristics) of astrocytes, oligodendroglia, and neurons. Their appearance, however, was spherical with few of the visible structures that characterize astrocytes and such9.
In 2007 a group of Japanese researchers induced skin wounds in mice and then i.v. injected MSCs (harvested from mice bred to produce Green Fluorescent Protein [GFP] in their tissues). They then detected GFP-positive cells at the wound sites which had specific biomarkers for various skin cell types including keratinocytes, endothelial cells, and pericytes. The treated mice demonstrated accelerated wound repair10.
And in another study from 2007, New York Medical College scientists reported that they had found evidence that bone marrow stem cells injected into transgenic mice who had experienced infarcts, i.e., blockage of blood flow to the heart with resulting damage, had engrafted, survived, and grown within the heart tissue by forming connections with resident heart muscle cells. This and other evidence showed that the bone marrow stem cells had transdifferentiated, i.e., converted from one cell type to another, and acquired cardiomyogenic (heart muscle-related) and vascular characteristics and traits (phenotypes) that helped to heal up the animal’s damaged hearts11.
Other studies have demonstrated that when bone marrow derived stem cells were injected into animal diabetic models they became insulin-producing cells12, and that when bone marrow-derived mesenchymal stem cells were injected into animals with (bleomycin-induced) lung damage13, they engrafted and differentiated into cells with specific, distinct lung cell phenotypes (characteristics).
Skeptics have been quick to point out that no matter how many millions of adult stem cells are infused into a patient, the total number that actually engrafts in target tissues and then differentiate or transdifferentiate into cell types that promote healing or such is too low to pull this off. This might be true if healing and restoration was solely dependent on large numbers of stem cells engrafting and transforming into cells that facilitate or otherwise support healing and such. However, both I and many others in the stem cell medicine trenches believe that the infused cells, both those that engraft and those that do not and are eventually cleared by the immune system or die off, have remediative, healing and restorative effects by virtue of the paracrine and other biologically powerful substances they secrete (Many of which were listed previously) including various cell signaling proteins called chemokines and bioactive lipids such as sphingosine-1-phosphate and ceramide-1-phosphate. Stem cells also secrete microRNA or miRNA, i.e., small non-coding RNA molecules which act to downregulate gene expression in a variety of ways, and RNA molecules which many researchers believe are the primary drivers of tissue and organ regeneration by virtue of their influence on paracrine signaling14.
In addition, stem cells also secrete microvesicles (MVs) or exosomes that transfer miRNAs to other cells which is thought to produce biological effects conducive to healing or restoration15.
In conclusion, I have found stem cell rich bone marrow aspirate concentrate (BMAC) to be a powerful clinical tool for treating not just orthopedic injuries and conditions, but neurologic and other acute and chronic maladies as well. The mix of stem cells and other cells in BMAC have produced salutary and even impressive to remarkable clinical outcomes in patients with cerebral palsy, traumatic brain injury (TBI), chronic stroke, Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig’s disease), and more treated in my clinic since 2005. Whether this is due to the stem cells engrafting and then transdifferentiating or differentiating into specific cell types, or to their secretion of paracrine or other factors, or both, there is in my opinion abundant clinical evidence that they are potent agents for effecting significant remediation, healing and restoration in sick and suffering people.
- Iafrati MD, Hallett JW, et al, ‘Early results and lessons learned from a multicenter, randomized, double-blind trial of bone marrow aspirate concentrate in critical limb ischemia’, J Vasc Surg. 2011 Dec;54(6):1650-8. Epub 2011 Oct 21. http://www.ncbi.nlm.nih.gov/pubmed/22019148
- Autobiographical entry by Nobel laureate Edward Donnall Thomas, MD on NobelPrize.Org http://www.nobelprize.org/nobel_prizes/medicine/laureates/1990/thomas-autobio.html
- Fernando Ramirez, David Steenblock, Anthony G. Payne and Lyn Darnall, Umbilical Cord Stem Cell Therapy for Cerebral Palsy, F. Ramirez et al (2006), Medical Hypotheses & Res. 3: 679-686. http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf
- Weimar IS, Miranda N, Muller EJ, et al, ‘Hepatocyte growth factor/scatter factor (HGF/SF) is produced by human bone marrow stromal cells and promotes proliferation, adhesion and survival of human hematopoietic progenitor cells (CD34+).’, Exp Hematol. 1998 Aug;26(9):885-94.
- Takahashi M, Li TS, Suzuki R, et al, ‘Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury’, Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H886-93. Epub 2006 Apr 7. http://ajpheart.physiology.org/content/291/2/H886.short
- “The Great Migration of Bone Marrow-Derived Stem Cells Toward the Ischemic Brain: Therapeutic Implications for Stroke and Other Neurological Disorders” Prog Neurobiol. Author manuscript; available in PMC 2012 October 1. Published in final edited form as:Prog Neurobiol. 2011 October; 95(2): 213–228. Published online 2011 August 30. doi: 10.1016/j.pneurobio.2011.08.005. PMCID: PMC3185169. NIHMSID: NIHMS321777 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185169/
- “Homing of stem cells to sites of inflammatory brain injury after intracerebral and intravenous administration: a longitudinal imaging study” Stem Cell Res Ther. 2010; 1(2): 17. Published online 2010 June 15. doi: 10.1186/scrt17 PMCID: PMC2905093
- Lymperi, S., Ferraro, F., & Scadden, D. T. (2010). The HSC niche concept has turned 31 Has our knowledge matured? Annals of the New York Academy of Sciences, 1192, 12–18. http://doi.org/10.1111/j.1749-6632.2009.05223.
- Li-Ru Zhao, Wei-Ming Duan, et al, ‘Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats’, Experimental Neurology, Volume 174, Issue 1, March 2002, Pages 11–20
- Sasaki M, Abe R, Fujita Y, et al, ‘Mesenchymal stem cells are recruited into wounded skin and contribute to wound repair by transdifferentiation into multiple skin cell type’, J Immunol. 2008 Feb 15;180(4):2581-7.
- Rota M, Kajstura J, Hosoda T, Bearzi C, et al, ‘Bone marrow cells adopt the cardiomyogenic fate in vivo’, Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17783-8. Epub 2007 Oct 26.
- Tang DQ, Cao LZ, et al, ‘In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow’, Diabetes. 2004 Jul;53(7):1721-32. 21.
- Mauricio Rojas, Jianguo Xu, Charles R. Woods, et al, ‘Bone Marrow–Derived Mesenchymal Stem Cells in Repair of the Injured Lung’, Am J Respir Cell Mol Biol. 2005 August; 33(2): 145–152. Published online 2005 May 12. doi: 10.1165/rcmb.2004-0330OC PMCID: PMC2715309. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715309/
- MZ Ratajczak, M Kucia, T Jadczyk, NJ Greco, et al, ‘Pivotal role of paracrine effects in stem cell therapies in regenerative medicine: can we translate stem cell-secreted paracrine factors and microvesicles into better therapeutic strategies?’, Leukemia (2012) 26, 1166 – 1173, http://126.96.36.199:9998/91keshi/Public/File/47/26-6/pdf/leu2011389a.pdf
- Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, et al. (2010) ‘Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs’, PLoS ONE 5(7): e11803. doi:10.1371/journal.pone.0011803http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0011803
- David T. Scadden, MD is Gerald and Darlene Jordan Professor of Medicine at Harvard University, founder and director of the Center for Regenerative Medicine at the Massachusetts General Hospital and with Douglas Melton, co-founder and co-director of the Harvard Stem Cell Institute and the Harvard University Department of Stem Cell and Regenerative Biology.
© 2015 by David A. Steenblock, D.O., Inc. All rights reserved.
ABOUT DR. STEENBLOCK
Dr. Steenblock earned his B.S. degree from Iowa State University, then an M.S. in Biochemistry and Doctor of Osteopathy (D.O.) degree from the College of Osteopathic Medicine and Surgery in Des Moines, Iowa. His post-doctoral training included three years at Case Western Reserve University, one year at the Oregon Health & Sciences University and a clinical Rotating Internship at Providence Hospital in Seattle, Washington. In addition, he did an externship at the University of Washington Department of Hematology/Oncology in 1969 which included work with stem cell-rich bone marrow. This program was run by Dr. Edward Donnall Thomas (who in 1990 was awarded the Nobel Prize in Medicine & Physiology).
During the late 1970s he founded the first integrative medicine clinic west of the Mississippi River. In the years since he has done pioneering clinical work including the use of hyperbaric oxygen therapy to treat stroke (starting in 1989), umbilical cord stem cell therapy (Mexico from 2003) and, since 2005, stem cell rich bone marrow aspirate concentrate (BMAC).
In October of 2015 he was awarded the Academy of Comprehensive Integrative Medicine’s (ACIM) “Lifetime Achievement Award” at their NeuroRegeneration Conference (Orlando, Florida) in recognition of his more than forty years of contributions to the world of medicine, especially in the realm of integrative medicine.
While at the ACIM conference, Dr. Steenblock gave a presentation on Amyotrophic Lateral Sclerosis (ALS) or “Lou Gehrig’s disease” that included data and insights gleamed from an observational study he did of 54 sporadic ALS patients he treated over a four year period (2011-2015). He shared evidence he found in the majority (52 of 54 sALS patients) that links spinal injury and subsequent reinjury to breaches in the blood-cerebrospinal barrier; breaches which then admit specific neurotoxic compounds, activated and damaged immune cells that secrete misfolded SOD1, as well as other cell and nerve cell toxic players (Some of which are selectively lethal to motor neurons). He also discussed his use of bone marrow stem cells and other means to repair these breaches, offset and reverse the damage, and counter the ALS disease process.
The spinal injuries/reinjuries and the symptoms and pathological damage Dr. Steenblock discovered provides both a unique risk factor and biomarker for sALS. If validated by subsequent research, this is something physicians and researchers can use to better diagnose sALS.
A paper concerning is in the process of being submitted to a top tier peer reviewed journal.