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Stem cells for stenosis – Dr. Marc Darrow is a Stem Cell …

By Sykes24Tracey

Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions aboutthis articleusing the contact form below.

I want to begin this article with a case study from our recently published research in theBiomedical Journal of Scientific & Technical Research.

Afterphysical assessment of her lower back, we determinedher pain was generated from a lumbosacral sprain. Not the narrowing of the L1-L5,S1

She had oneBone marrow derived stem cell treatment and at first follow up two weeks after the injections,the patient experienced no pain or stiffness and reported 90% total improvement. Approximately a year after treatment, she felt evenbetter, and stated that she was able to perform aerobics and line dancing for an hour and a half a day with no pain. She reportedinfrequent stiffness, but not as severe as it was prior to treatment.

Her resting and active pain were 0/10 and functionality score was 39/40.(1)

This was one document case in the medical literature. Over the years we have helped many people avoid a stenosis surgery they did not want or possibly did not even need.

Despite the fact that many studies insist that surgical treatment is the best option for lumbar spinal stenosis, a startling study was published in the medical journal Spine. In this study, American, Canadian and Italian researchers published their evidence:

We have very little confidence to conclude whether surgicaltreatmentor a conservative approach is better forlumbarspinal stenosis, and we can provide no new recommendations to guide clinical practice. . .However, it should be noted that the rate of side effects ranged from 10% to 24% in surgical cases, and no side effects were reported for any conservativetreatment. (2)

In the above research it should be pointed out the comparison between lumbar surgery and conservative treatments did not include stem cell therapy. They included the traditional conservative treatments including physical therapy, cortisone injections, pain medications and others listed below.

One of the reasons surgery may be no better than conservative care is that the surgery tried to fix a problem that was not there: Pain.

In the medical journal Osteoarthritis and Cartilage,doctors reported that many asymptomatic individuals, those with no pain or other challenges, have radiographic lumbar spinal stenosis. In other words they only have lumbar spinal stenosis on the MRI.

The doctors noted:

A diagnosis of spinal stenosis can be frightening because of the implications that a surgery may be needed to avoid paralysis.It is important to note that in instances where stenosis is so severe that the patient has lost circulation to the legs or bladder control a surgical consult should be made immediately.

In the December 2017 edition of the medical journal Spine, doctors from the University of Pittsburgh and University Toronto reported these observations in patients seeking non-surgical treatments for lumbar spinal stenosis.

Individuals with lumbar spinal stenosis may believe misinformation and information from non-medical sources, especially when medical providers do not spend sufficient time explaining the disease process and the reasoning behind treatment strategies. Receiving individualized care focused on self-management led to fewer negative emotions toward care and the disease process. Clinicians should be prepared to address all three of these aspects when providing care to individuals with lumbar spinal stenosis.(4)

Back pain can certainly cause anxiety, depression, and catastrophizing thoughts. The people in this study wanted education and involvement in their choice of treatment. I hope I can provide some for you here in this article.

Lumbar Spinal Stenosis is a narrowing of the space between vertebrae where the spinal cord and the spinal nerves travel. It is a diagnostic term to describe lower back pain with or without weakness and loss of sensation in the legs. It is a very common condition brought on mostly by aging and the accompanying degeneration of the spine.

In the recommended surgical procedures for spinal stenosis, two choices are the most favored.

A paper published in October 2017 gives a good outline where conservative medicine is in the treatment of Lumbar stenosis. It is from doctors at the University of South Carolina

This is indeed a fair assessment of SOME of the treatment options available to patients.However, not all doctors agree. At New York University in June 2017 research, doctors wrote:

The highest levels of evidence do not support minimally invasive surgery over open surgery for cervical orlumbardisc herniation. However, minimally invasive surgery fusion demonstrates advantages along with higher revision and hospital readmission rates. These results should optimize informed decision-making regarding minimally invasive surgery versus open spine surgery, particularly in the current advertising climate greatly favoring minimally invasive surgery.(6)

Researchers at theUniversity of Sydneysay that the evidence for recommending lumbar spinal surgery as the best option to patients is lacking and it is possible that a sham or placebo surgery can deliver the same results.(7)

In the research I cited at the top of this article, doctors at the Italian Scientific Spine Institute in Milanwrote: We cannot conclude on the basis of this review whether surgical or nonsurgical treatment is better for individuals with lumbar spinal stenosis. We can however report on the high rate of effects reported in three of five surgical groups and that no side effects were reported for any of the conservative treatment options.(8)

Considering the majority of these procedures are unnecessarily being performed for degenerative disc disease alone, spine surgeons should be increasingly asked why they are offering these operations to their patients

Ateam of Japanese researchers found thatpatients with lumbar spinal stenosiswho do not improve after nonsurgical treatments are typically treated surgically using decompressive surgeryand spinal fusion surgery. Unfortunately the researchers could not determine if the surgery had any benefit either.(9)Maybe the patients problem was not the stenosis?

Now lets go to another paper that has more of an opinion: From Dr. Nancy Epstein ofWinthrop University Hospital:

Surgeons at Leiden University Medical Centre in the Netherlandsspeculate that doctors go into a diagnosis oflumbar spinal stenosis with the thought that there is osteoarthritis a bony overgrowth on the spinal nerves. Once determined, the symptoms of patients can be categorized into two groups; regional (low back pain, stiffness, and so on) or radicular (spinal stenosis mainly presenting as neurogenic claudication nerve inflammation).

In the patients who primarily complain of radiculopathy (radiating leg pain) with an stable spine, a decompression surgery may be recommendedto removebonefrom around thenerve root to give the nerve root more space.The surgeons warn of thefear that surgery to a stable spine will make it unstable.(11)

Afusion procedure to limit the movement between two vertebrae and hopefully stop the compression of nerves is another option. As mentioned by independent research above surgery for spinal stenosis should onlybe considered after conservative therapies have been exhausted.Surgical treatment of lumbar spinal disorders, including fusion, is associated with a substantial risk of intraoperative and perioperative complications,as pointed out in the research by surgeons from Catholic University in Rome.(12)

Bone growth occurs in the spine because the bone is trying to stabilize the spine from excessive movement or laxity. Fusion surgery is recommended as a means to accelerate that type of stabilization. Regenerative medicine includingPRP andStem Cell Therapy(watch the video)works in a completely different way. Theystabilize the spine by strengthening the often forgotten and underappreciated spinal ligaments and tendons.These techniques help stabilize the spine, which is imperative as unstable joints can lead to or further exacerbate the arthritis that causes spinal stenosis.

In the medical journal Insights into imaging, researchers wrote of the four factors associated with the degenerative changes of the spine that cause spinal canal stenosis:

The same research suggests that these conditions can prevent the formation of new tissue (collagen) which can initiate repair.(13)

Collagen is of course the elastic material of skin and ligaments. Here the association between collagen interruption and spinal stenosis can be made to show spinal instability can be THE problem of symptomatic stenosis.

A fascinating study on what damaged spinal ligaments can do

A fascinating study in the Asian Spine Journal investigated the relationship between ligamentum flavum thickening and lumbar segmental instability, disc degeneration, and facet joint osteoarthritis. Ligament thickening is the result of chronic inflammation. Chronic ligament inflammation is the result of a ligament injury that is not healing.

What these researchers found was a significant correlation between ligamentum flavum thickness, spinal instability and disc degeneration. More so, the worse the degenerative disc disease, the worse the ligamentum flavum thickness.(14)

PRP and stem cells address the problem of ligament damage and inflammation. Addressing these problems address the problems of spinal instability. Addressing the problems of spinal instability can address the problems of spinal and cervical stenosis.

A leading provider of bone marrow derived stem cell therapy, Platelet Rich Plasma and Prolotherapy11645 WILSHIRE BOULEVARD SUITE 120, LOS ANGELES, CA 90025

PHONE: (800) 300-9300

1 Darrow M, Shaw BS. Treatment of Lower Back Pain with Bone Marrow Concentrate. Biomed J Sci&Tech Res 7(2)-2018. BJSTR. MS.ID.001461. DOI: 10.26717/ BJSTR.2018.07.001461.

2 Zaina F, TomkinsLane C, Carragee E, Negrini S. Surgical versus nonsurgical treatment for lumbar spinal stenosis. The Cochrane Library. 2016 Jul 1.

3 Lynch AD, Bove AM, Ammendolia C, Schneider M. Individuals with lumbar spinal stenosis seek education and care focused on self-managementresults of focus groups among participants enrolled in a randomized controlled trial. The Spine Journal. 2017 Dec 12

4 Ishimoto Y, Yoshimura N, Muraki S, Yamada H, Nagata K, Hashizume H, Takiguchi N, Minamide A, Oka H, Kawaguchi H, Nakamura K. Associations between radiographic lumbar spinal stenosis and clinical symptoms in the general population: the Wakayama Spine Study. Osteoarthritis and cartilage. 2013 Jun 1;21(6):783-8.

5Patel J, Osburn I, Wanaselja A, Nobles R. Optimal treatment for lumbar spinal stenosis: an update. Current Opinion in Anesthesiology. 2017 Oct 1;30(5):598-603.

6 Vazan M, Gempt J, Meyer B, Buchmann N, Ryang YM. Minimally invasive transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion: a technical description and review of the literature. Acta Neurochir (Wien). 2017 Jun;159(6):1137-1146

7Machado GC, Ferreira PH, Yoo RI, et al. Surgical options for lumbar spinal stenosis. Cochrane Database Syst Rev. 2016 Nov 1;11:CD012421.

8Zaina F, Tomkins-Lane C, Carragee E, Negrini S. Surgical Versus Nonsurgical Treatment for Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2016 Jul 15;41(14):E857-68.

9 Inoue G, Miyagi M, Takaso M. Surgical and nonsurgical treatments for lumbar spinal stenosis. Eur J Orthop Surg Traumatol. 2016 Oct;26(7):695-704. doi: 10.1007/s00590-016-1818-3. Epub 2016 Jul 25.

10 Epstein NE. More nerve root injuries occur with minimally invasive lumbar surgery: Lets tell someone. Surg Neurol Int. 2016 Jan 25;7(Suppl 3):S96-S101. doi: 10.4103/2152-7806.174896. eCollection 2016.

11Overdevest GM, Moojen WA, Arts MP, Vleggeert-Lankamp CL, Jacobs WC, Peul WC.Management of lumbar spinal stenosis: a survey among Dutch spine surgeons. Acta Neurochir (Wien). 2014 Aug 7. [Epub ahead of print]

12.Proietti L, Scaramuzzo L, Schiro GR, Sessa S, Logroscino CA. Complications in lumbar spine surgery: A retrospective analysis. Indian J Orthop. 2013 Jul;47(4):340-5. doi: 10.4103/0019-5413.114909.

13 Kushchayev SV, Glushko T, Jarraya M, et al. ABCs of the degenerative spine.Insights into Imaging. 2018;9(2):253-274. doi:10.1007/s13244-017-0584-z.

14 Yoshiiwa T, Miyazaki M, Notani N, Ishihara T, Kawano M, Tsumura H. Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis.Asian Spine Journal. 2016;10(6):1132-1140. doi:10.4184/asj.2016.10.6.1132.2373

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October 14th, 2018

stem cell | Definition, Types, Uses, Research, & Facts …

By Sykes24Tracey

Stem cell, an undifferentiated cell that can divide to produce some offspring cells that continue as stem cells and some cells that are destined to differentiate (become specialized). Stem cells are an ongoing source of the differentiated cells that make up the tissues and organs of animals and plants. There is great interest in stem cells because they have potential in the development of therapies for replacing defective or damaged cells resulting from a variety of disorders and injuries, such as Parkinson disease, heart disease, and diabetes. There are two major types of stem cells: embryonic stem cells and adult stem cells, which are also called tissue stem cells.

Adult Cardiac Stem Cells Don’t Exist: Study | The …

By Sykes24Tracey

Cardiac stem cell research has a turbulent history. Studies revealing the presence of regenerative progenitors in adult rodents hearts formed the basis of numerous clinical trials, but several experiments have cast doubt on these cells ability to produce new tissue. Some scientists are now lauding the results of a report published in April in Circulation as undeniable evidence against the idea that resident stem cells can give rise to new cardiomyocytes.

The concept of [many] clinical trials arose from the basic science in labs of a few individuals more than 15 years ago, and that basic science is whats now being called into question, says Jeffery Molkentin, a cardiovascular biologist at Cincinnati Childrens Hospital who penned an editorial about the latest work.

The first evidence supporting the notion of cardiac stem cells in adults emerged in the early 2000s, when researchers reported that cells derived from bone marrow or adult heart expressing the protein c-kit could give rise to new muscle tissue when injected into damaged myocardium in rodents. These studies caused some controversy right from the start, Molkentin says. The main reason that this struck a raw nerve with people is because we already know that heart, in human patients, doesnt regenerate itself after an infarct.

Early skepticism arose in 2004, when two separate groups of researchers published back-to-back papers refuting the claims that bone marrowderived c-kit cells could regenerate damaged heart tissue. Still, the concept of endogenous cardiac stem cells remained a mainstream idea until Molkentin and his colleagues published a study in 2014 reporting that c-kit cells in the adult mouse heart almost never produced new cardiomyocytes, says Bin Zhou, a cell biologist at the Chinese Academy of Sciences and a coauthor of the new study.

Although Molkentins findings were replicated shortly afterwards by two independent groups (including Zhous), some researchers held fast to the idea that cardiac progenitors could regenerate injured heart tissue. Earlier this year, a team of researchersincluding Bernardo Nadal-Ginard and Daniele Torella of Magna Graecia University in Italy and several other scientists who conducted the early work on c-kit cellspublished a paper reporting the flaws in the cell lineage tracing technique employed by Molkentin, Zhou, and their colleagues. For example, they noted that the method, which involved tagging c-kitexpressing cells and their progeny with a fluorescent marker, compromised the gene required to express the c-kit protein, impairing the progenitors regenerative abilities.

In the new Circulationstudy, Zhou and his colleagues used a different approach to examine endogenous stem cell populations in mice. Instead of tagging c-kit cells, the team applied a technique that would fluorescently label nonmyocytes and newly generated muscle cells a different color from existing myocytes. This method allowed the researchers to investigate all proposed stem cell populations, rather than specifically addressing c-kit cells. We wanted to ask the broader question of whether there are any stem cells in the adult heart, Zhou says.

These experiments revealed that, while nonmyocytes generate cardiomyocytes in mouse embryos, they do not give rise to new muscle cells in adult rodents hearts. The results also address the concerns raised about c-kit lineage tracing, Zhou tells The Scientist. We think our system can conclude that nonmyocytes cannot become myocytes in adults in homeostasis and after injury.

Torella says that hes not convinced by Zhous evidence. The main issue, he explains, is that the researchers did not explicitly test whether cardiac stem cells were indeed labeled as nonmyocytes to ensure that they were not inadvertently tagging them as myocytes instead.

Molkentin disagrees with this critique, stating that the only way the system would label a myocyte progenitor as a myocyte is if it was no longer a true stem cell, but instead an immature myocyte. Zhous group uses an exhausting and very rigorous genetic approach, he adds. My opinion is that we need to go back to the bench and conduct additional research to truly understand the mechanisms at play to better inform how we design the next generation of clinical trials.

Other scientists note that stem cells may not need to become new myocytes to help repair the injured heart. According to Phillip Yang, a cardiologist at Stanford University who did not take part in the work, many scientists now agree that stem cells are not regenerating damaged cardiomyocytes. Instead, he explains, a growing body of research now supports an alternative theory, which posits that progenitor cells secrete small molecules called paracrine factors that help repair injured heart cells. (Yang is involved in several stem cell clinical trials).

When you inject these stem cells, its pretty incontrovertible that they help heart function in a mouse injury model, Yang says. But the truth is, most of these cells are dead upon arrival [to the site of injury]. So the question is: Why is heart function still improving if these cells are dying?

Y. Li et al., Genetic lineage tracing of nonmyocyte population by dual recombinases, Circulation, 138:793-805, 2018.

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September 8th, 2018

Mending a Broken Heart: Stem Cells and Cardiac Repair …

By Sykes24Tracey

Charles A. Goldthwaite, Jr., Ph.D.

Cardiovascular disease (CVD), which includes hypertension, coronary heart disease (CHD), stroke, and congestive heart failure (CHF), has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza epidemic.1 In 2002, CVD claimed roughly as many lives as cancer, chronic lower respiratory diseases, accidents, diabetes mellitus, influenza, and pneumonia combined. According to data from the 19992002 National Health and Nutrition Examination Survey (NHANES), CVD caused approximately 1.4 million deaths (38.0 percent of all deaths) in the U.S. in 2002. Nearly 2600 Americans die of CVD each day, roughly one death every 34 seconds. Moreover, within a year of diagnosis, one in five patients with CHF will die. CVD also creates a growing economic burden; the total health care cost of CVD in 2005 was estimated at $393.5 billion dollars.

Given the aging of the U.S. population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes,2,3 CVD will continue to be a significant health concern well into the 21st century. However, improvements in the acute treatment of heart attacks and an increasing arsenal of drugs have facilitated survival. In the U.S. alone, an estimated 7.1 million people have survived a heart attack, while 4.9 million live with CHF.1 These trends suggest an unmet need for therapies to regenerate or repair damaged cardiac tissue.

Ischemic heart failure occurs when cardiac tissue is deprived of oxygen. When the ischemic insult is severe enough to cause the loss of critical amounts of cardiac muscle cells (cardiomyocytes), this loss initiates a cascade of detrimental events, including formation of a non-contractile scar, ventricular wall thinning (see Figure 6.1), an overload of blood flow and pressure, ventricular remodeling (the overstretching of viable cardiac cells to sustain cardiac output), heart failure, and eventual death.4 Restoring damaged heart muscle tissue, through repair or regeneration, therefore represents a fundamental mechanistic strategy to treat heart failure. However, endogenous repair mechanisms, including the proliferation of cardiomyocytes under conditions of severe blood vessel stress or vessel formation and tissue generation via the migration of bone-marrow-derived stem cells to the site of damage, are in themselves insufficient to restore lost heart muscle tissue (myocardium) or cardiac function.5 Current pharmacologic interventions for heart disease, including beta-blockers, diuretics, and angiotensin-converting enzyme (ACE) inhibitors, and surgical treatment options, such as changing the shape of the left ventricle and implanting assistive devices such as pacemakers or defibrillators, do not restore function to damaged tissue. Moreover, while implantation of mechanical ventricular assist devices can provide long-term improvement in heart function, complications such as infection and blood clots remain problematic.6 Although heart transplantation offers a viable option to replace damaged myocardium in selected individuals, organ availability and transplant rejection complications limit the widespread practical use of this approach.

Figure 6.1. Normal vs. Infarcted Heart. The left ventricle has a thick muscular wall, shown in cross-section in A. After a myocardial infarction (heart attack), heart muscle cells in the left ventricle are deprived of oxygen and die (B), eventually causing the ventricular wall to become thinner (C).

2007 Terese Winslow

The difficulty in regenerating damaged myocardial tissue has led researchers to explore the application of embryonic and adult-derived stem cells for cardiac repair. A number of stem cell types, including embryonic stem (ES) cells, cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells, mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated to varying extents as possible sources for regenerating damaged myocardium. All have been tested in mouse or rat models, and some have been tested in large animal models such as pigs. Preliminary clinical data for many of these cell types have also been gathered in selected patient populations.

However, clinical trials to date using stem cells to repair damaged cardiac tissue vary in terms of the condition being treated, the method of cell delivery, and the primary outcome measured by the study, thus hampering direct comparisons between trials.7 Some patients who have received stem cells for myocardial repair have reduced cardiac blood flow (myocardial ischemia), while others have more pronounced congestive heart failure and still others are recovering from heart attacks. In some cases, the patient's underlying condition influences the way that the stem cells are delivered to his/her heart (see the section, quot;Methods of Cell Deliveryquot; for details). Even among patients undergoing comparable procedures, the clinical study design can affect the reporting of results. Some studies have focused on safety issues and adverse effects of the transplantation procedures; others have assessed improvements in ventricular function or the delivery of arterial blood. Furthermore, no published trial has directly compared two or more stem cell types, and the transplanted cells may be autologous (i.e., derived from the person on whom they are used) or allogeneic (i.e., originating from another person) in origin. Finally, most of these trials use unlabeled cells, making it difficult for investigators to follow the cells' course through the body after transplantation (see the section quot;Considerations for Using These Stem Cells in the Clinical Settingquot; at the end of this article for more details).

Despite the relative infancy of this field, initial results from the application of stem cells to restore cardiac function have been promising. This article will review the research supporting each of the aforementioned cell types as potential source materials for myocardial regeneration and will conclude with a discussion of general issues that relate to their clinical application.

In 2001, Menasche, et.al. described the successful implantation of autologous skeletal myoblasts (cells that divide to repair and/or increase the size of voluntary muscles) into the post-infarction scar of a patient with severe ischemic heart failure who was undergoing coronary artery bypass surgery.8 Following the procedure, the researchers used imaging techniques to observe the heart's muscular wall and to assess its ability to beat. When they examined patients 5 months after treatment, they concluded that treated hearts pumped blood more efficiently and seemed to demonstrate improved tissue health. This case study suggested that stem cells may represent a viable resource for treating ischemic heart failure, spawning several dozen clinical studies of stem cell therapy for cardiac repair (see Boyle, et.al.7 for a complete list) and inspiring the development of Phase I and Phase II clinical trials. These trials have revealed the complexity of using stem cells for cardiac repair, and considerations for using stem cells in the clinical setting are discussed in a subsequent section of this report.

The mechanism by which stem cells promote cardiac repair remains controversial, and it is likely that the cells regenerate myocardium through several pathways. Initially, scientists believed that transplanted cells differentiated into cardiac cells, blood vessels, or other cells damaged by CVD.911 However, this model has been recently supplanted by the idea that transplanted stem cells release growth factors and other molecules that promote blood vessel formation (angiogenesis) or stimulate quot;residentquot; cardiac stem cells to repair damage.1214 Additional mechanisms for stem-cell mediated heart repair, including strengthening of the post-infarct scar15 and the fusion of donor cells with host cardiomyocytes,16 have also been proposed.

Regardless of which mechanism(s) will ultimately prove to be the most significant in stem-cell mediated cardiac repair, cells must be successfully delivered to the site of injury to maximize the restored function. In preliminary clinical studies, researchers have used several approaches to deliver stem cells. Common approaches include intravenous injection and direct infusion into the coronary arteries. These methods can be used in patients whose blood flow has been restored to their hearts after a heart attack, provided that they do not have additional cardiac dysfunction that results in total occlusion or poor arterial flow.12, 17 Of these two methods, intracoronary infusion offers the advantage of directed local delivery, thereby increasing the number of cells that reach the target tissue relative to the number that will home to the heart once they have been placed in the circulation. However, these strategies may be of limited benefit to those who have poor circulation, and stem cells are often injected directly into the ventricular wall of these patients. This endomyocardial injection may be carried out either via a catheter or during open-heart surgery.18

To determine the ideal site to inject stem cells, doctors use mapping or direct visualization to identify the locations of scars and viable cardiac tissue. Despite improvements in delivery efficiency, however, the success of these methods remains limited by the death of the transplanted cells; as many as 90% of transplanted cells die shortly after implantation as a result of physical stress, myocardial inflammation, and myocardial hypoxia.4 Timing of delivery may slow the rate of deterioration of tissue function, although this issue remains a hurdle for therapeutic approaches.

Embryonic and adult stem cells have been investigated to regenerate damaged myocardial tissue in animal models and in a limited number of clinical studies. A brief review of work to date and specific considerations for the application of various cell types will be discussed in the following sections.

Because ES cells are pluripotent, they can potentially give rise to the variety of cell types that are instrumental in regenerating damaged myocardium, including cardiomyocytes, endothelial cells, and smooth muscle cells. To this end, mouse and human ES cells have been shown to differentiate spontaneously to form endothelial and smooth muscle cells in vitro19 and in vivo,20,21 and human ES cells differentiate into myocytes with the structural and functional properties of cardiomyocytes.2224 Moreover, ES cells that were transplanted into ischemically-injured myocardium in rats differentiated into normal myocardial cells that remained viable for up to four months,25 suggesting that these cells may be candidates for regenerative therapy in humans.

However, several key hurdles must be overcome before human ES cells can be used for clinical applications. Foremost, ethical issues related to embryo access currently limit the avenues of investigation. In addition, human ES cells must go through rigorous testing and purification procedures before the cells can be used as sources to regenerate tissue. First, researchers must verify that their putative ES cells are pluripotent. To prove that they have established a human ES cell line, researchers inject the cells into immunocompromised mice; i.e., mice that have a dysfunctional immune system. Because the injected cells cannot be destroyed by the mouse's immune system, they survive and proliferate. Under these conditions, pluripotent cells will form a teratoma, a multi-layered, benign tumor that contains cells derived from all three embryonic germ layers. Teratoma formation indicates that the stem cells have the capacity to give rise to all cell types in the body.

The pluripotency of ES cells can complicate their clinical application. While undifferentiated ES cells may possibly serve as sources of specific cell populations used in myocardial repair, it is essential that tight quality control be maintained with respect to the differentiated cells. Any differentiated cells that would be used to regenerate heart tissue must be purified before transplantation can be considered. If injected regenerative cells are accidentally contaminated with undifferentiated ES cells, a tumor could possibly form as a result of the cell transplant.4 However, purification methodologies continue to improve; one recent report describes a method to identify and select cardiomyocytes during human ES cell differentiation that may make these cells a viable option in the future.26

This concern illustrates the scientific challenges that accompany the use of all human stem cells, whether derived from embryonic or adult tissues. Predictable control of cell proliferation and differentiation requires additional basic research on the molecular and genetic signals that regulate cell division and specialization. Furthermore, long-term cell stability must be well understood before human ES-derived cells can be used in regenerative medicine. The propensity for genetic mutation in the human ES cells must be determined, and the survival of differentiated, ES-derived cells following transplantation must be assessed. Furthermore, once cells have been transplanted, undesirable interactions between the host tissue and the injected cells must be minimized. Cells or tissues derived from ES cells that are currently available for use in humans are not tissue-matched to patients and thus would require immunosuppression to limit immune rejection.18

While skeletal myoblasts (SMs) are committed progenitors of skeletal muscle cells, their autologous origin, high proliferative potential, commitment to a myogenic lineage, and resistance to ischemia promoted their use as the first stem cell type to be explored extensively for cardiac application. Studies in rats and humans have demonstrated that these cells can repopulate scar tissue and improve left ventricular function following transplantation.27 However, SM-derived cardiomyocytes do not function in complete concert with native myocardium. The expression of two key proteins involved in electromechanical cell integration, N-cadherin and connexin 43, are downregulated in vivo,28 and the engrafted cells develop a contractile activity phenotype that appears to be unaffected by neighboring cardiomyocytes.29

To date, the safety and feasibility of transplanting SM cells have been explored in a series of small studies enrolling a collective total of nearly 100 patients. Most of these procedures were carried out during open-heart surgery, although a couple of studies have investigated direct myocardial injection and transcoronary administration. Sustained ventricular tachycardia, a life-threatening arrhythmia and unexpected side-effect, occurred in early implantation studies, possibly resulting from the lack of electrical coupling between SM-derived cardiomyocytes and native tissue.30,31 Changes in preimplantation protocols have minimized the occurrence of arrhythmias in conjunction with the use of SM cells, and Phase II studies of skeletal myoblast therapy are presently underway.

In 2001, Jackson, et.al. demonstrated that cardiomyocytes and endothelial cells could be regenerated in a mouse heart attack model through the introduction of adult mouse bone marrow-derived stem cells.9 That same year, Orlic and colleagues showed that direct injection of mouse bone marrow-derived cells into the damaged ventricular wall following an induced heart attack led to the formation of new cardiomyocytes, vascular endothelium, and smooth muscle cells.11 Nine days after transplanting the stem cells, the newly-formed myocardium occupied nearly 70 percent of the damaged portion of the ventricle, and survival rates were greater in mice that received these cells than in those that did not. While several subsequent studies have questioned whether these cells actually differentiate into cardiomyocytes,32,33 the evidence to support their ability to prevent remodeling has been demonstrated in many laboratories.7

Based on these findings, researchers have investigated the potential of human adult bone marrow as a source of stem cells for cardiac repair. Adult bone marrow contains several stem cell populations, including hematopoietic stem cells (which differentiate into all of the cellular components of blood), endothelial progenitor cells, and mesenchymal stem cells; successful application of these cells usually necessitates isolating a particular cell type on the basis of its' unique cell-surface receptors. In the past three years, the transplantation of bone marrow mononuclear cells (BMMNCs), a mixed population of blood and cells that includes stem and progenitor cells, has been explored in more patients and clinical studies of cardiac repair than any other type of stem cell.7

The results from clinical studies of BMMNC transplantation have been promising but mixed. However, it should be noted that these studies have been conducted under a variety of conditions, thereby hampering direct comparison. The cells have been delivered via open-heart surgery and endomyocardial and intracoronary catheterization. Several studies, including the Bone Marrow Transfer to Enhance ST-Elevation Infarct Regeneration (BOOST) and the Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) trials, have shown that intracoronary infusion of BMMNCs following a heart attack significantly improves the left ventricular (LV) ejection fraction, or the volume of blood pumped out of the left ventricle with each heartbeat.3436 However, other studies have indicated either no improvement in LV ejection fraction upon treatment37 or an increased LV ejection fraction in the control group.38 An early study that used endomyocardial injection to enhance targeted delivery indicated a significant improvement in overall LV function.39 Discrepancies such as these may reflect differences in cell preparation protocols or baseline patient statistics. As larger trials are developed, these issues can be explored more systematically.

Mesenchymal stem cells (MSCs) are precursors of non-hematopoietic tissues (e.g., muscle, bone, tendons, ligaments, adipose tissue, and fibroblasts) that are obtained relatively easily from autologous bone marrow. They remain multipotent following expansion in vitro, exhibit relatively low immunogenicity, and can be frozen easily. While these properties make the cells amenable to preparation and delivery protocols, scientists can also culture them under special conditions to differentiate them into cells that resemble cardiac myocytes. This property enables their application to cardiac regeneration. MSCs differentiate into endothelial cells when cultured with vascular endothelial growth factor40 and cardiomyogenic (CMG) cells when treated with the dna-demethylating agent, 5-azacytidine.41 More important, however, is the observation that MSCs can differentiate into cardiomyocytes and endothelial cells in vivo when transplanted to the heart following myocardial infarct (MI) or non-injury in pig, mouse, or rat models.4245 Additionally, the ability of MSCs to restore functionality may be enhanced by the simultaneous transplantation of other stem cell types.43

Several animal model studies have shown that treatment with MSCs significantly increases myocardial function and capillary formation.5,41 One advantage of using these cells in human studies is their low immunogenicity; allogeneic MSCs injected into infarcted myocardium in a pig model regenerated myocardium and reduced infarct size without evidence of rejection.46 A randomized clinical trial implanting MSCs after MI has demonstrated significant improvement in global and regional LV function,47 and clinical trials are currently underway to investigate the application of allogeneic and autologous MSCs for acute MI and myocardial ischemia, respectively.

Recent evidence suggests that the heart contains a small population of endogenous stem cells that most likely facilitate minor repair and turnover-mediated cell replacement.7 These cells have been isolated and characterized in mouse, rat, and human tissues.48,49 The cells can be harvested in limited quantity from human endomyocardial biopsy specimens50 and can be injected into the site of infarction to promote cardiomyocyte formation and improvements in systolic function.49 Separation and expansion ex vivo over a period of weeks are necessary to obtain sufficient quantities of these cells for experimental purposes. However, their potential as a convenient resource for autologous stem cell therapy has led the National Heart, Lung, and Blood Institute to fund forthcoming clinical trials that will explore the use of cardiac stem cells for myocardial regeneration.

The endothelium is a layer of specialized cells that lines the interior surface of all blood vessels (including the heart). This layer provides an interface between circulating blood and the vessel wall. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that are recruited into the peripheral blood in response to tissue ischemia.4 EPCs are precursor cells that express some cell-surface markers characteristic of mature endothelium and some of hematopoietic cells.19,5153 EPCs home in on ischemic areas, where they differentiate into new blood vessels; following a heart attack, intravenously injected EPCs home to the damaged region within 48 hours.12 The new vascularization induced by these cells prevents cardiomyocyte apoptosis (programmed cell death) and LV remodeling, thereby preserving ventricular function.13 However, no change has been observed in non-infarcted regions upon EPC administration. Clinical trials are currently underway to assess EPC therapy for growing new blood vessels and regenerating myocardium.

Several other cell populations, including umbilical cord blood (UCB) stem cells, fibroblasts (cells that synthesize the extracellular matrix of connective tissues), and peripheral blood CD34+ cells, have potential therapeutic uses for regenerating cardiac tissue. Although these cell types have not been investigated in clinical trials of heart disease, preliminary studies in animal models indicate several potential applications in humans.

Umbilical cord blood contains enriched populations of hematopoietic stem cells and mesencyhmal precursor cells relative to the quantities present in adult blood or bone marrow.54,55 When injected intravenously into the tail vein in a mouse model of MI, human mononuclear UCB cells formed new blood vessels in the infarcted heart.56 A human DNA assay was used to determine the migration pattern of the cells after injection; although they homed only to injured areas within the heart, they were also detected in the marrow, spleen, and liver. When injected directly into the infarcted area in a rat model of MI, human mononuclear UCB cells improved ventricular function.57 Staining for CD34 and other markers found on the cell surface of hematopoietic stem cells indicated that some of the cells survived in the myocardium. Results similar to these have been observed following the injection of human unrestricted somatic stem cells from UCB into a pig MI model.58

Adult peripheral blood CD34+ cells offer the advantage of being obtained relatively easily from autologous sources.59 Although some studies using a mouse model of MI claim that these cells can transdifferentiate into cardiomyocytes, endothelial cells, and smooth muscle cells at the site of tissue injury,60 this conclusion is highly contested. Recent studies that involve the direct injection of blood-borne or bone marrow-derived hematopoietic stem cells into the infarcted region of a mouse model of MI found no evidence of myocardial regeneration following injection of either cell type.33 Instead, these hematopoietic stem cells followed traditional differentiation patterns into blood cells within the microenvironment of the injured heart. Whether these cells will ultimately find application in myocardial regeneration remains to be determined.

Autologous fibroblasts offer a different strategy to combat myocardial damage by replacing scar tissue with a more elastic, muscle-like tissue and inhibiting host matrix degradation.4 The cells may be manipulated to express muscle-specific transcription factors that promote their differentiation into myotubes such as those derived from skeletal myoblasts.61 One month after these cells were implanted into the post-infarction scar in a rat model of MI, they occupied a large portion of the scar but were not functionally integrated.61 Although the effects on ventricular function were not evaluated in this study, authors noted that modified autologous fibroblasts may ultimately prove useful in elderly patients who have a limited population of autologous skeletal myoblasts or bone marrow stem cells.

As these examples indicate, many types of stem cells have been applied to regenerate damaged myocardium. In select applications, stem cells have demonstrated sufficient promise to warrant further exploration in large-scale, controlled clinical trials. However, the current breadth of application of these cells has made it difficult to compare and contextualize the results generated by the various trials. Most studies published to date have enrolled fewer than 25 patients, and the studies vary in terms of cell types and preparations used, methods of delivery, patient populations, and trial outcomes. However, the mixed results that have been observed in these studies do not necessarily argue against using stem cells for cardiac repair. Rather, preliminary results illuminate the many gaps in understanding of the mechanisms by which these cells regenerate myocardial tissue and argue for improved characterization of cell preparations and delivery methods to support clinical applications.

Future clinical trials that use stem cells for myocardial repair must address two concerns that accompany the delivery of these cells: 1) safety and 2) tracking the cells to their ultimate destination(s). Although stem cells appear to be relatively safe in the majority of recipients to date, an increased frequency of non-sustained ventricular tachycardia, an arrhythmia, has been reported in conjunction with the use of skeletal myoblasts.30,6264 While this proarrhythmic effect occurs relatively early after cell delivery and does not appear to be permanent, its presence highlights the need for careful safety monitoring when these cells are used. Additionally, animal models have demonstrated that stem cells rapidly diffuse from the heart to other organs (e.g., lungs, kidneys, liver, spleen) within a few hours of transplantation,65,66 an effect observed regardless of whether the cells are injected locally into the myocardium. This migration may or may not cause side-effects in patients; however, it remains a concern related to the delivery of stem cells in humans. (Note: Techniques to label stem cells for tracking purposes and to assess their safety are discussed in more detail in other articles in this publication).

In addition to safety and tracking, several logistical issues must also be addressed before stem cells can be used routinely in the clinic. While cell tracking methodologies allow researchers to determine migration patterns, the stem cells must target their desired destination(s) and be retained there for a sufficient amount of time to achieve benefit. To facilitate targeting and enable clinical use, stem cells must be delivered easily and efficiently to their sites of application. Finally, the ease by which the cells can be obtained and the cost of cell preparation will also influence their transition to the clinic.

The evidence to date suggests that stem cells hold promise as a therapy to regenerate damaged myocardium. Given the worldwide prevalence of cardiac dysfunction and the limited availability of tissue for cardiac transplantation, stem cells could ultimately fulfill a large-scale unmet clinical need and improve the quality of life for millions of people with CVD. However, the use of these cells in this setting is currently in its infancymuch remains to be learned about the mechanisms by which stem cells repair and regenerate myocardium, the optimal cell types and modes of their delivery, and the safety issues that will accompany their use. As the results of large-scale clinical trials become available, researchers will begin to identify ways to standardize and optimize the use of these cells, thereby providing clinicians with powerful tools to mend a broken heart.

Chapter 5|Table of Contents|Chapter 7

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June 21st, 2018

Next Steps for Cardiac Stem Cells – MedStar Heart …

By Sykes24Tracey

To determine why the first stem cell trials were not providing the anticipated therapeutic potential, all variables, such as which stem cells were used, and how they were developed and administered, were open to consideration, says Dr. Epstein.

A key issue was the use of autologous stem cells in all previous studies. Studies demonstrated these old stem cells are functionally defective when compared to stem cells obtained from young healthy individuals. So harvesting a healthy young donors bone marrow and growing the resident stem cells might produce more robust cells.

However, giving a patient allogenic stem cells raised an important issue: whether such cells will be rejected by an immune response. But research showed mesenchymal stem cells (MSCs), a type of adult stem cell, have been designed by nature to be stealth bombers, explainsDr. Epstein. They express molecules on their surface that prevent the body from recognizing the cells as foreign, so the patient does not reject the donated MSCs.

To further explore and refine potential stem cell cardiovascular therapies, MHVI expanded the translational research team to include Michael Lipinski, MD, PhD, an expert in molecular biology and scientific lead for preclinical research at the MedStar Cardiovascular Research Network, and Dror Luger, PhD, an expert in immunology and inflammatory responses. By bringing together these diverse areas of expertise, we forged a team with the potential to produce research that could lead to important breakthroughs in understanding how stem cells might work and thereby provide more successful treatment of patients with cardiac disease, says Dr. Epstein.

CardioCell, a San Diego-based stem cell company focused on stem cell therapy for cardiovascular disease, found that MSCs grew faster and showed improved function when cultured in a reduced oxygen environment. Stem cells typically grow in the body, in bone marrow and other tissues, in a low oxygen environmentonly five percent oxygen, as opposed to room air, which is about 20 percent, explains Dr. Lipinski. All previous stem cell trials used cells exposed to, and grown under, room air oxygen conditions.

Using CardioCells low oxygen-grown MSCs, the MHVI scientists demonstrated biologically important effects occurred, even when the MSCs were administered intravenously. This mode of administration was previously rejected by scientists who thought cells would be trapped in the first capillary bed they traversedthe lungsand never reach the heart.

However, the MHVI team demonstrated a small percentage of these IV administered MSCs did reach the heart, where they could exert beneficial effects. The cells seek out inflamed cardiac tissue after a heart attack because they upregulate receptors that allow them to be attracted to and penetrate inflamed tissue in high numbers, says Dr. Luger.

The investigators also found the cells residing in other tissues could provide other benefits. It has been shown that a heart attack activates the immune and inflammatory systems, including those in the spleen, explains Dr. Luger. The systemic anti-inflammatory effects produced by MSCs in the spleen, lungs and other tissues caused by the molecules secreted by the MSCs could exert positive effects as well. Dr. Epstein added that such anti-inflammatory effects could also benefit the excessive inflammatory activities that exist in many heart failure patients.

For the clinical heart failure trial, MHVI is partnering with CardioCell, which will grow and provide stem cells already used in Phase I and 2a clinical trials and approved by the Food and Drug Administration.

As an extension of their stem cell work, the MHVI investigators are building on the fact that any beneficial effect of adult stem cells will not derive from their transformation into heart muscle, but rather from the molecules they secrete; these, in turn, stimulate pathways favoring tissue healing. The team is investigating the use of liposomes as therapeutic delivery vehicles for these secreted products, which include those with anti-inflammatory and angiogenesis activities.

If successful, using MSCs for anti-inflammatory and immune-modulatory effects could have implicationsfor many different diseases, including arthritis and autoimmune diseases like rheumatoid arthritis. Dr. Epstein cautions that a great deal of research is yet to be done before such applications can be routinely used to treat patients with these conditions. For now, they hope the current studies in heart failure patients will demonstrate effectiveness. If so, Dr. Epstein says, it changes the whole playing field for stem cells.

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June 11th, 2018

Press Releases Viacyte, Inc.

By Sykes24Tracey

12.15.17CIRM Grants ViaCyte $1.4M to Create Immune-Evasive Pluripotent Stem Cell Lines

SAN DIEGO, December 15, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced that the California Institute for Regenerative Medicine (CIRM) approved a grant of $1.4 million to support the initial development of []

ViaCyte is developing PEC-Direct to address the urgent medical need of high-risk type 1 diabetes and provide a potentially life-saving therapy SAN DIEGO,December 6, 2017 ViaCyte today announced that CONNECT, a premier innovation company []

SAN DIEGO, October 4, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced upcoming company presentations at the Cell and Gene Meeting on the Mesa and the BIO Investor Forum. In addition, ViaCyte []

SAN DIEGO, September 28, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced that the California Institute for Regenerative Medicine (CIRM) approved a grant of $20 million to support the clinical development of []

Developing PEC-Direct to address urgent medical need in patients with high-risk type 1 diabetes SAN DIEGO, September 21, 2017 Today, ViaCyte announced that its PEC-Direct product candidate has been selected as one of three []

SAN DIEGO, September 7, 2017 ViaCyte, Inc., a privately-held, leading regenerative medicine company, today announced upcoming scientific presentations. ViaCyte is developing novel stem cell-derived islet replacement therapies for insulin-requiring diabetes. ViaCytes product candidates have []

San Diego, August 1, 2017 ViaCyte, Inc., a privately-held, leading regenerative medicine company, announced today that the first patients have been implanted with the PEC-Direct product candidate, a novel islet cell replacement therapy in []

SAN DIEGO, June 15, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced a presentation at the International Society for Stem Cell Research (ISSCR) 2017 Annual Meeting in Boston. ViaCyte is developing novel []

San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, announced today that the U.S. Food and Drug Administration (FDA) has allowed the companys Investigational New Drug Application (IND) for the []

San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, announced today $10 million in financing to support operations. Participants in the financing included Asset Management Partners, W.L. Gore & Associates, []

New York and San Diego, May 22, 2017 ViaCyte, Inc., a privately-held leading regenerative medicine company, and JDRF, the leading global organization funding type 1 diabetes research, jointly announced today JDRF grant funding to []

ViaCyte to also present at World Advanced Therapies and Regenerative Medicine Congress in London SAN DIEGO, April 24, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced two presentations on April 27 at []

SAN DIEGO, California and NEWARK, Delaware, March 29, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, and W. L. Gore & Associates, Inc. (Gore), a global materials science company, today announced a collaborative research []

SAN DIEGO and SAN FRANCISCO, February 23, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, and Beyond Type 1, a not-for-profit advocacy and education group for those living with type 1 diabetes, today []

SAN DIEGO, February 21, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced four presentations at upcoming healthcare events. ViaCyte is advancing two novel cell replacement therapies as long-term diabetes treatments. ViaCytes product []

President and CEO, Paul Laikind, PhD to present at 2017 Biotech Showcase SAN DIEGO, January 4, 2017 ViaCyte, Inc., a privately-held regenerative medicine company, today announced the addition of twenty-two new patents in 2016. []

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April 29th, 2018

Stem Cell Treatments – Brain and Spinal Cord

By Sykes24Tracey

Because stem cells have the potential to generate cells designed to replace or repair cells damaged by spinal cord injury, advocates of stem cell research and treatment believe that the benefits far outweigh the negative aspects. Opponents of this research and treatment, however, typically bring up the issue of embryonic stem cells, which are harvested from embryos and fetal tissue. Accordingly, they feel the use of these embryonic stem cells is not moral or ethical. Because stem cells are harvested from embryos and fetal tissue, they feel it is not moral or ethical. Secondly, opponents are concerned about the health and safety of the participants in human stem cell research trials. It is important to note that non-embryonic stem cells, called somatic or adult stem cells, have recently been identified in various body tissues including brain, bone marrow, blood vessels, and various organ tissues.

Lets talk about how stem cell research could possibly impact spinal cord injury. Stem cell research came on the scene in 1998, when a group of scientists isolated pluripotent stem cells from human embryos and grew them in a culture. Since then, specialists have discovered that stem cells can become any of the 200 specialized cells in the body, giving them the ability to repair or replace damaged cells and tissues. While not yet known to have the diversification potential of embryonic stem cells, adult somatic cells act similarly and are generating excitement in the research and medical community.

When all is said and done, could stem cell treatment be the miracle cure for spinal cord injury and paralysis? Well, we dont really know. Because of all of the controversy, much of the evidence that shows stem cells can be turned into specific cells for transplantation involves only mice, whose cells are significantly different than human cells. Nevertheless, some initial research points to promising results. One hurdle that remains to be cleared is whether an immune response would reject a cellular transplant.

Ultimately, no one yet knows the extent to which stem cell treatment could help spinal cord injury and paralysis. Scientists remain hopeful, but currently there just hasnt been enough research done to substantiate any particular result. Additional research needs to be done before we have more definitive answers.

Again, we just dont know. Much of the answer depends upon whether the political process and moral debate continues to limitand put the hold onthe amount of research done. At this point its impossible to say for sure whenor even ifstem cells will be useful in the treatment of paralysis.

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April 15th, 2018

What is a Stem Cell Transplant (Bone Marrow Transplant)? | Cancer.Net

By Sykes24Tracey

A stem cell transplant is a treatment for some types of cancer. For example, you might have one if you have leukemia, multiple myeloma, or some types of lymphoma. Doctors also treat some blood diseases with stem cell transplants.

In the past, patients who needed a stem cell transplant received a bone marrow transplant because the stem cells were collected from the bone marrow. Today, stem cells are usually collected from the blood, instead of the bone marrow. For this reason, they are now more commonly called stem cell transplants.

A part of your bones called bone marrow makes blood cells. Marrow is the soft, spongy tissue inside bones. It contains cells called hematopoietic stem cells (pronounced he-mah-tuh-poy-ET-ick). These cells can turn into several other types of cells. They can turn into more bone marrow cells. Or they can turn into any type of blood cell.

Certain cancers and other diseases keep hematopoietic stem cells from developing normally. If they are not normal, neither are the blood cells that they make. A stem cell transplant gives you new stem cells. The new stem cells can make new, healthy blood cells.

The main types of stem cell transplants and other options are discussed below.

Autologous transplant. Doctors call this an AUTO transplant. This type of stem cell transplant may also be called high-dose chemotherapy with autologous stem cell rescue.

In an AUTO transplant, you get your own stem cells after doctors treat the cancer. First, your health care team collects stem cells from your blood and freezes them. Next, you have powerful chemotherapy, and rarely, radiation therapy. Then, your health care team thaws your frozen stem cells. They put them back in your blood through a tube placed in a vein (IV).

It takes about 24 hours for your stem cells to reach the bone marrow. Then they start to grow, multiply, and help the marrow make healthy blood cells again.

Allogeneic transplantation. Doctors call this an ALLO transplant.

In an ALLO transplant, you get another persons stem cells. It is important to find someone whose bone marrow matches yours. This is because you have certain proteins on your white blood cells called human leukocyte antigens (HLA). The best donor has HLA proteins as much like yours as possible.

Matching proteins make a serious condition called graft-versus-host disease (GVHD) less likely. In GVHD, healthy cells from the transplant attack your cells. A brother or sister may be the best match. But another family member or volunteer might work.

Once you find a donor, you receive chemotherapy with or without radiation therapy. Next, you get the other persons stem cells through a tube placed in a vein (IV). The cells in an ALLO transplant are not typically frozen. So, doctors can give you the cells as soon after chemotherapy or radiation therapy as possible.

There are 2 types of ALLO transplants. The best type for each patient depends his or her age and health and the type of disease being treated.

Ablative, which uses high-dose chemotherapy

Reduced intensity, which uses milder doses of chemotherapy

If your health care team cannot find a matched adult donor, there are other options. Research is ongoing to determine which type of transplant will work best for different patients.

Umbilical cord blood transplant. This may be an option if you cannot find a donor match. Cancer centers around the world use cord blood.

Parent-child transplant and haplotype mismatched transplant. These types of transplants are being used more commonly. The match is 50%, instead of near 100%. Your donor might be a parent, child, brother, or sister.

Your doctor will recommend an AUTO or ALLO transplant based mostly on the disease you have. Other factors include the health of your bone marrow and your age and general health. For example, if you have cancer or other disease in your bone marrow, you will probably have an ALLO transplant. In this situation, doctors do not recommend using your own stem cells.

Choosing a transplant is complicated. You will need help from a doctor who specializes in transplants. So you might need to travel to a center that does many stem cell transplants. Your donor might need to go, too. At the center, you talk with a transplant specialist and have an examination and tests. Before a transplant, you should also think about non-medical factors. These include:

Who can care for you during treatment

How long you will be away from work and family responsibilities

If your insurance pays for the transplant

Who can take you to transplant appointments

Your health care team can help you find answers to these questions.

The information below tells you the main parts of AUTO and ALLO transplants. Your health care team usually does the steps in order. But sometimes certain steps happen in advance, such as collecting stem cells. Ask your doctor what to expect before, during, and after a transplant.

A doctor puts a thin tube called a transplant catheter in a large vein. The tube stays in until after the transplant. Your health care team will collect stem cells through this tube and give chemotherapy and other medications through the tube.

You get injections of a medication to raise your number of white blood cells. White blood cells help your body fight infections.

Your health care team collects stem cells, usually from your blood.

Time: 1 to 2 weeks

Where its done: Clinic or hospital building. You do not need to stay in the hospital overnight.

Time: 5 to 10 days

Where its done: Clinic or hospital. At many transplant centers, patients need to stay in the hospital for the duration of the transplant, usually about 3 weeks. At some centers, patients receive treatment in the clinic and can come in every day.

Time: Each infusion usually takes less than 30 minutes. You may receive more than 1 infusion.

Where its done: Clinic or hospital.

Time: approximately 2 weeks

Where its done: Clinic or hospital. You might be staying in the hospital or you might not.

Time: Varies based on how the stem cells are collected

Where its done: Clinic or hospital

Time: 5 to 7 days

Where its done: Many ALLO transplants are done in the hospital.

Time: 1 day

Where its done: Clinic or hospital.

You take antibiotics and other drugs. This includes medications to prevent graft-versus-host disease. You get blood transfusions through your catheter if needed. Your health care team takes care of any side effects from the transplant.

After the transplant, patients visit the clinic frequently at first and less often over time.

Time: Varies

For an ablative transplant, patients are usually in the hospital for about 4 weeks in total.

For a reduced intensity transplant, patients are in the hospital or visit the clinic daily for about 1 week.

The words successful transplant might mean different things to you, your family, and your doctor. Below are 2 ways to measure transplant success.

Your blood counts are back to safe levels. A blood count is the number of red cells, white cells, and platelets in your blood. A transplant makes these numbers very low for 1 to 2 weeks. This causes risks of:

Infection from low numbers of white cells, which fight infections

Bleeding from low numbers of platelets, which stop bleeding

Tiredness from low numbers of red cells, which carry oxygen

Doctors lower these risks by giving blood and platelet transfusions after a transplant. You also take antibiotics to help prevent infections. When the new stem cells multiply, they make more blood cells. Then your blood counts improve. This is one way to know if a transplant is a success.

It controls your cancer. Doctors do stem cell transplants with the goal of curing disease. A cure may be possible for some cancers, such as some types of leukemia and lymphoma. For other patients, remission is the best result. Remission is having no signs or symptoms of cancer. After a transplant, you need to see your doctor and have tests to watch for any signs of cancer or complications from the transplant.

Talking often with the doctor is important. It gives you information to make health care decisions. The questions below may help you learn more about stem cell transplant. You can also ask other questions that are important to you.

Which type of stem cell transplant would you recommend? Why?

If I will have an ALLO transplant, how will we find a donor? What is the chance of a good match?

What type of treatment will I have before the transplant? Will radiation therapy be used?

How long will my treatment take? How long will I stay in the hospital?

How will a transplant affect my life? Can I work? Can I exercise and do regular activities?

How will we know if the transplant works?

What if the transplant doesnt work? What if the cancer comes back?

What are the side effects? This includes short-term, such as during treatment and shortly after. It also includes long-term, such as years later.

What tests will I need later? How often will I need them?

If I am worried about managing the costs of treatment, who can help me with these concerns?

Bone Marrow Aspiration and Biopsy

Making Decisions About Cancer Treatment

Donating Blood and Platelets

Donating Umbilical Cord Blood

Explore BMT

Be the Match: National Marrow Donor Program

Blood & Marrow Transplant Information Network

U.S. Department of Health and Human Services: Understanding Transplantation as a Treatment Option

National Bone Marrow Transplant Link

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April 12th, 2018

Bone marrow | anatomy | Britannica.com

By Sykes24Tracey

Bone marrow, also called myeloid tissue, soft, gelatinous tissue that fills the cavities of the bones. Bone marrow is either red or yellow, depending upon the preponderance of hematopoietic (red) or fatty (yellow) tissue. In humans the red bone marrow forms all of the blood cells with the exception of the lymphocytes, which are produced in the marrow and reach their mature form in the lymphoid organs. Red bone marrow also contributes, along with the liver and spleen, to the destruction of old red blood cells. Yellow bone marrow serves primarily as a storehouse for fats but may be converted to red marrow under certain conditions, such as severe blood loss or fever. At birth and until about the age of seven, all human marrow is red, as the need for new blood formation is high. Thereafter, fat tissue gradually replaces the red marrow, which in adults is found only in the vertebrae, hips, breastbone, ribs, and skull and at the ends of the long bones of the arm and leg; other cancellous, or spongy, bones and the central cavities of the long bones are filled with yellow marrow.

Red marrow consists of a delicate, highly vascular fibrous tissue containing stem cells, which differentiate into various blood cells. Stem cells first become precursors, or blast cells, of various kinds; normoblasts give rise to the red blood cells (erythrocytes), and myeloblasts become the granulocytes, a type of white blood cell (leukocyte). Platelets, small blood cell fragments involved in clotting, form from giant marrow cells called megakaryocytes. The new blood cells are released into the sinusoids, large thin-walled vessels that drain into the veins of the bone. In mammals, blood formation in adults takes place predominantly in the marrow. In lower vertebrates a number of other tissues may also produce blood cells, including the liver and the spleen.

Because the white blood cells produced in the bone marrow are involved in the bodys immune defenses, marrow transplants have been used to treat certain types of immune deficiency and hematological disorders, especially leukemia. The sensitivity of marrow to damage by radiation therapy and some anticancer drugs accounts for the tendency of these treatments to impair immunity and blood production.

Examination of the bone marrow is helpful in diagnosing certain diseases, especially those related to blood and blood-forming organs, because it provides information on iron stores and blood production. Bone marrow aspiration, the direct removal of a small amount (about 1 ml) of bone marrow, is accomplished by suction through a hollow needle. The needle is usually inserted into the hip or sternum (breastbone) in adults and into the upper part of the tibia (the larger bone of the lower leg) in children. The necessity for a bone marrow aspiration is ordinarily based on previous blood studies and is particularly useful in providing information on various stages of immature blood cells. Disorders in which bone marrow examination is of special diagnostic value include leukemia, multiple myeloma, Gaucher disease, unusual cases of anemia, and other hematological diseases.

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February 16th, 2018

Stories of Hope: Spinal Cord Injury | California’s Stem …

By Sykes24Tracey

Espaol

Katie Sharify had six days to decide: would she let her broken body become experimental territory for a revolutionary new approacheven if it was unlikely to do her any good? The question was barely fathomable. She had only just regained consciousness. A week earlier, she had been in a car crash that damaged her spine, leaving her with no sensation from the chest down. In the confusion and emotion of those first few days, the family thought that the treatment would fix Katie's mangled spinal cord. But that was never the goal. The objective, in fact, was simply to test the safety of the treatment. The misunderstanding a cure, and then no cure -- plunged the 23-year-old from hope to despair. And yet she couldn't let the idea of this experimental approach go.

Just days after learning that she would never walk again, that she would never know when her bladder was full, that she would not feel it if she broke her ankle, she was thinking about the next girl who might lie in this bed with a spinal injury. If Katie walked away from this experimental approachwhat would happen to others that came after her?

Her medical team provided a crash course in stem cell therapy to help Katie think things through. In this case the team had taken stem cells obtained from a five-day old embryo and converted them into cells that support communication between the brain and body. Those cells would be transplanted into the injured spines. Earlier experiments in animal models suggested that, once in place, these cells might help regenerate a patient's own nerve tissue. But before scientists could do the experiment, they needed to make sure the technique they were using was safe by using a small number of cells, too few to likely have any benefit. And that's why they wanted Katies help in this CIRM-funded trial. They explained the risks. They explained that she was unlikely to derive any benefit. They explained that she was just a step along the way. Even so, Katie agreed. She became the fifth patient in what's called a Phase I trial: part of the long, arduous process required to bring new therapies to patients. Shortly after she was treated the trial stopped enrolling patients for financial reasons.

That was in 2011. Since then, she has been through an intensive physical therapy program to increase her strength. She went back to college. She tried skiing and surfing. She learned how to make life work in this new body. But as she rebuilt her life she wondered if taking part in the clinical trial had truly made a difference.

"I was frustrated at first. I felt hopeless. Why did I even do this? Why did I even bother?" But soon she began to see how small advances were moving the science forward. She learned the steep challenges that await new therapies. Then in 2014, she discovered that the research she participated in was deemed to be safe and is about to enter its next phase, thanks to a $14.3 million grant from CIRM to Asterias Biotherapeutics. "This has been my wish from day one," Katie says.

"It gives me so much hope to know there is an organization that cares and wants to push these therapies forward, that wants to find a cure or a treatment," she says. "I don't know what I would do if I thought nobody cared, nobody wanted to take any risks, nobody wanted to put any funding into spinal cord injuries.

"I really have to have some ray of hope to hold onto, and for me, CIRM is that ray of hope."

For more information about CIRM-funded spinal cord injury research, visit our fact sheet.

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February 7th, 2018

Regeneration of the entire human skin using transgenic …

By Sykes24Tracey

Epidermolysis bullosais is rare, but the charity DEBRA, which campaigns for EB patients, estimates half a million people are affected around the world.

There are different forms of epidermolysis bullosa, including simplex, dystrophic and, as in this case, junctional.

Each is caused by different genetic faults leading to different building blocks of skin being missing.

Prof Michele De Luca, from the University of Modena and Reggio Emilia, told the BBC: The gene is different, the protein is different and the outcome may be different [for each form of EB] so we need formal clinical trials.

But if they can make it work, it could be a therapy that lasts a lifetime.

An analysis of the structure of the skin of the first patient to get 80% of his replaced has discovered a group of long-lived stem cells are that constantly renewing his genetically modified skin.

Genetically modified skin cells were grown to make skin grafts totalling 0.85 sq m (9 sq ft). It took three operations over that winter to cover 80% of the childs body in the new skin. But 21 months later, the skin is functioning normally with no sign of blistering.

Nature Regeneration of the entire human epidermis using transgenic stem cells

Junctional epidermolysis bullosa (JEB) is a severe and often lethal genetic disease caused by mutations in genes encoding the basement membrane component laminin-332. Surviving patients with JEB develop chronic wounds to the skin and mucosa, which impair their quality of life and lead to skin cancer. Here we show that autologous transgenic keratinocyte cultures regenerated an entire, fully functional epidermis on a seven-year-old child suffering from a devastating, life-threatening form of JEB. The proviral integration pattern was maintained in vivo and epidermal renewal did not cause any clonal selection. Clonal tracing showed that the human epidermis is sustained not by equipotent progenitors, but by a limited number of long-lived stem cells, detected as holoclones, that can extensively self-renew in vitro and in vivo and produce progenitors that replenish terminally differentiated keratinocytes. This study provides a blueprint that can be applied to other stem cell-mediated combined ex vivo cell and gene therapies

SOURCES BBC News, Nature

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December 13th, 2017

Fully Functional Skin Grown From Stem Cells Could Double …

By Sykes24Tracey

If theres one thing skin can do well, its grow. Each month our body replaces its skin,nearly 19 million skin cells per inch a feat thats been far less successful in the lab. However, the days of lab-grown skin may not be too far off:Recently, a team of Japanese scientists not only grew fully functional skin tissue, but also transplanted it successfully onto living organisms.

Though the technique has only been tested on mice so far, the team predicts it could one day revolutionize treatments for burn victims, or other patients that have suffered catastrophic skin damage. On a less gruesome note, the team says it may also be useful in treating a more common condition: baldness.

The study, published online in Science Advances, involved researchers from the Riken Center for Developmental Biology and Tokyo University of Science, among other Japanese institutions. The researchers first step was to transform cells from the gums of mice into induced pluripotent stem cells, or adult cells that have been genetically reprogrammed back into an embryonic stem cell state. This is done by forcing the cells to express genes associated with embryonic stem cells. Once transformed into stem cells, they can then be manipulated to become any type of cell in the body.

Next, the team placed the stem cells into a petri dish, where they added the molecule Wnt10b, which coaxed the stem cells to form into clusters that resembled a developing embryo. These clusters were then transplanted into mice bred without a fully functional immune system, which ensured that their bodies did not reject the transplant. Here, they underwent cell differentiation, the process by which unspecialized cells become specialized. In this case, they were becoming skin cells, and once the process had begun, the cells were transplanted again onto the skin of new mice, where they made normal connections with surrounding nerve and muscle tissue to become fully functional skin.

Skin is one of the largest and most important organs in the human body, yet its also one of the most difficult to treat when its damaged. Current treatment options involve painful skin grafts or barely functional artificial skin. According to the new study, however, being able to grow skin in the lab will account for more than just skin's use in protecting our inner bodies. The lab-grown skin also showed the ability to develop hair follicles and sweat glands, which play a role in controlling body temperature and keeping the skin moisturized it's in these areas that skin repair has often fallen short.

"Up until now, artificial skin development has been hampered by the fact that the skin lacked the important organs, such as hair follicles and exocrine glands, lead researcher, Takashi Tsuji of the RIKEN Center for Developmental Biology,said in a recent statement. With this new technique, we have successfully grown skin that replicates the function of normal tissue.

In addition to revolutionizing skin repair, the technique may also help those with certain types of hair loss. The study noted that using Wnet10b on the stem cells resulted in the production of a higher number of hair follicles than previous attempts at growing skin. Within two weeks of receiving the transplanted skin, the mice began to grow hair. Dr. Seth Orlow, chair of dermatology at NYU School of Medicine in New York City, told U.S. News Health that this feature of the lab-grown skin could be manipulated to help patients with both alopecia and pattern baldness.

In theory, we may eventually be able to create structures like hair follicles and other skin glands that could be transplanted back to people who need them, Orlow told U.S. Health News.

According to The Washington Post, the technique is still about five to 10 years away from being safe and effective enough to be used on humans. But with about 95 percent of men and 50 percent of women experiencing some degree of baldness over the course of their lives, its a safe bet that there will be no shortage of eager customers ready to get their hair back when the treatment is approved for use in doctors offices.

Source: Takagi R, Ishimaru J, Sugawara A, et al. Bioengineering a 3D integumentary organ system from iPS cells using an in vivo transplantation model. Science Advances . 2016

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December 13th, 2017

What are stem cells and how will they be used to treat the …

By Sykes24Tracey

Stem cell research is often controversial but it has also led to incredible medical progress in recent years.

Stem cell research is at defining moment. Although it can be controversial and does raise a lot of important ethical issues, this area of medical science has been characterised by a number of important advances, ever since the first embryonic stem cells were isolated from mice in the 1980s. In the near future, it could reshape the way we treat some of the worlds most debilitating diseases.

Stem cells have already been used as treatment for a number of years think bone marrow transplant and they have the potential to help with many other medical conditions. They could also prove crucial for scientists wishing to understand more about human biology and development.

Studies using stem cells have benefited from important media coverage in recent years and many of them hailed as breakthroughs. However, the reality is often more complex, and a number of scientific and ethical challenges often stand in the way of successes in animal models being replicated in humans.

IBTimes UK takes a look at what stem cell research is, what it is used for and what the future looks like.

Stem cells could be defined as building block cells that have not yet differentiated into one cell type and could develop into many different cell types. Stem cells can continue to divide almost indenitely.

There are two main types of stem cells: embryonic stem cells and adult stem cells.

Embryonic stem cells were first isolated in mice in the early 1980s at the University of Cambridge. All developing embryos contains a number of stem cells that can go on to develop into different cell types. In humans, these cells can be isolated from around five days after the egg has been fertilised around 50 to 100 stem cells are present at that stage.

These cells are isolated from embryos that have been donated by couples who have been through IVF and have extra embryos left which were not used during the treatment.

Stem cells are also found in adults, particularly in the bone marrow, the blood, the eyes, the brain and the muscles. They are also known as somatic stem cells.

They can also differentiate into other cells, but into a much more limited number than embryonic stem cells. They range from cells that are able to form different kinds of tissues to more specialised cells that form just some of the cells of a particular tissue or organ. They also have the ability to divide and reproduce indefinitely.

19th Place: Dr Gist F Croft, Lauren Pietilla, Stephanie Tse, Dr. Szilvia Galgoczi, Maria Fenner, Dr Ali H. Brivanlou, Rockefeller University, Brivanlou Laboratory New York, New York, USA: Human neural rosette primordial brain cells, differentiated from embryonic stem cells Confocal, 10x (Dr Gist F Croft, Lauren Pietilla, Stephanie Tse, Dr. Szilvia Galgoczi, Maria Fenner, Dr Ali H. Brivanlou)

Scientists have also found a way to make induced pluripotent stem cells cells taken from any adult tissue and genetically modified to behave like an embryonic stem cell (and thus able to differentiate into any cell type). The term pluripotant refers to the fact that the stem cells can produce almost all of the cells in the body.

To create these induced pluripotent stem cells, researchershave learnt to reprogramme the genes of human adult cells. A major 2007 US study, found that introducing 14 genes could reprogramme the cells to become stem cells, and the researchers then narrowed this down to four genes. Subsequent studies have built on this knowledge to find new, safer ways to turn adult cells into pluripotant stem cells.

Stem cells are already used to help a number of patients around the world. For nearly 50 years, they have been used in the form of bone marrow transplants.

Indeed, bone marrow contains stem cells that can produce many different blood cells. A bone marrow transplant can be used to treat people with blood cancers or genetic blood disorders, such as sickle cell anaemia. The stem cell turn into healthy blood cells that can help the patient. Some hospitals also use stem cells to grow skin grafts for patients with life-threatening burns. It is also possible to receive a stem cell therapy based on limbal stem cells (in the eye) to repair damaged corneas.

Stem cells are also very useful for scientists conducting basic research on diseases, as they can be used to model a large number of conditions. Recent studies have used stem cells to model the nerve cells that are lost in Alzheimers disease or to model deafness or Autism Spectrum disorder.

Scientists have gained a better understanding of blood stem cells (Alden Chadwick/Flickr)

A number of treatment using stem cells has been tested by researchers around the world. A type of patients that could be helped by stems cells are those suffering from spinal cord injuries. Stem cell therapy for spinal cord repair could be used to promote the growth of nerve cells directly or to transplant cells that protect the nerves and help them function.

One of most important studies in this area was published in October 2010. tested the used embryonic stem cells on patients in the US who had sustained a spinal cord injury in the previous 14 days. Preliminary findings were encouraging.

Studies have also been conducted to assess the safety and efficacy of stem cells in helping patients who suffered a stroke. The idea is that stem cells could help in rehabilitation after a persons brain has been damaged by the stroke. Stem cells have also been investigated to treat diseases such as MS, diabetes and to reverse ageing.

Beyond clinical trials, which still remain limited in number, many of the preliminary research opens up a number of very interesting perspectives. One of the main area of interest is growing organs in the lab from tissues created from stem cells. These organs may one day be used for transplantation in humans.

Recently, stem cells have been shown to present an interest to improve fertility treatments with the creation of a new technique in mice in-vitro gametogenesis. The idea is to create eggs and sperm using pluripotant stem cells.

By La Surugue

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November 25th, 2017

Stem Cell-Based Therapy for Cartilage Regeneration and …

By Sykes24Tracey

Our initial application established the goals of our project and the reasons for our study. Arthritis is the result of degeneration of cartilage (the tissue lining the joints) and leads to pain and limitation of function. Arthritis and other rheumatic diseases are among the most common of all health conditions and are the number one cause of disability in the United States. The annual economic impact of arthritis in the U.S. is estimated at over $120 billion, representing more than 2% of the gross domestic product. The prevalence of arthritic conditions is also expected to increase as the population increases and ages in the coming decades. Current treatment options for osteoarthritis are limited to pain reduction and joint replacement surgery. Stem cells have tremendous potential for treating disease and replacing or regenerating the diseased tissue. In this project our objective is to use cells derived from stems cells to treat arthritis. We have completed our experiments as per our proposed timeline and have met milestones outlined in our grant submission. We have established conditions for converting stem cells into cartilage tissue cells that can repair bone and cartilage defects in laboratory models. We have identified several cell lines with the highest potential for tissue repair. We optimized culture conditions to generate the highest quality of tissue. In our initial experiments we found no evidence of cell rejection response in vivo. We have testing efficacy of the most promising cell lines in regenerating healthy repair tissue in cartilage defects and have selected a preclinical candidate.The next step is to plan safety and efficacy studies for the preclinical phase, identify collaborators with the facilities to obtain, process, and provide cell-based therapies, and identify clinical collaborators in anticipation of clinical trials. If necessary we will also identify commercialization partners. We also anticipate that stem cells implanted in arthritic cartilage will treat the arthritis in addition to producing tissue to heal the defect in the cartilage. An approach that heals cartilage defects as well as treats the underlying arthritis would be very valuable. If our research is successful, this could lead to first treatment of osteoarthritis that alters the progression of the disease. This treatment would have a huge impact on the large numbers of patients who suffer from arthritis as well as in reducing the significant economic burden created by arthritis.

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November 22nd, 2017

Heart Failure and Transplant Program New Jersey

By Sykes24Tracey

New Jersey's Premier Heart Transplant Program

The Barnabas Health Heart Failure and Transplant program is the most experienced and comprehensive center in New Jersey. It has been at the forefront of highly specialized care for more than twenty years. Our cardiac surgeons and heart specialists' expertise has made RWJBarnabas Health a regional and national training center for physicians, nurses and emergency services technicians.

Dr. Joseph Clemente, host of MHC-TV, interviews Mark J. Zucker, M.D., J.D., Director, Heart Failure Treatment and Transplant Program at Newark Beth Israel Medical Center. They discuss getting a heart transplant, other treatments such as the Left Ventricular Assist Device (LVAD), and about stem cell research ongoing today.

Learn about CardioMEMS, a new treatment for heart failure

Barnabas Health Heart Centers Earn Recognition from American Heart Association in Heart Failure Treatment

The Barnabas Health Heart Centers provide progressive heart failure management that optimizes the patient's transition to home and empowers them to improve their heart health. Advanced practice nurses contact patients within days of discharge and facilitate daily medical monitoring, education, and counseling. Patient-centered programs bring together all the medical resources necessary to combat heart failure and the reduction in hospital readmission rates has been significant. Heart failure clinics are based at all Barnabas Health hospitals.

Clinical trials provide patients with access for breakthrough medications, devices, and therapies, while being continually monitored and evaluated. Our participation in new cardiac stem cell research for patients with refractory angina and chronic myocardial ischemia may someday help the heart heal itself. Improved technology has made positive outcomes with ECMO more likely both at our center and nationally, and has resulted in increased referrals for this critical care.

The Newark Beth Israel Medical Center heart transplant program is one of the top ten heart transplant centers in the United States with survival rates that consistently meet or exceed national benchmarks. The center is at the forefront of improving the quality of life for transplant candidates and recipients, as well as increasing access to transplant. Our unique work in establishing successful protocols for discontinuing steroid medications for immunosuppression is improving the medical management and survival rates for transplant recipients worldwide. Noninvasive gene expression testing offers an alternative technique for assessing immunosuppression and predicting rejection. The center is also part of groundbreaking research that is exploring innovating methods for preserving donor organs for transplant.

Implantable VADs are placed for myocardial recovery, bridge to transplant, and destination therapy. Because the VAD program is totally integrated with heart failure and transplant services, patients are thoroughly and continually evaluated for all treatment options. The heart transplant center's experience has made it a principal site for clinical research trials of the latest generation of mechanical assist devices and a regional VAD transplantation training site. With virtually all FDA-approved and investigational implantable devices available, patients receive the device that meets their individual needs.

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October 23rd, 2017

Skin Stem Cells – Methods and Protocols | Kursad Turksen …

By Sykes24Tracey

During the last decade, an increased interest in somatic stem cells has led to a flurry of research on one of the most accessible tissues of the body: skin. Much effort has focused on such topics as understanding the heterogeneity of stem cell pools within the epidermis and dermis, and their comparative utility in regenerative medicine applications. In Skin Stem Cells: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study skin stem cells. These include methods and techniques for the isolation, maintenance and characterization of stem cell populations from skin. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, Skin Stem Cells: Methods and Protocols seeks to aid scientists in the further understanding of these diverse cell types and the translation of their biological potential to the in vivo setting.

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October 15th, 2017

Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

By Sykes24Tracey

On Saturday morning, a convoy of vintage Ford Broncos carrying some very precious cargo made a stop at La Caadas Descanso Gardens.

En route from Childrens Hospital Los Angeles, the motorcade was led by a golden 1971 Bronco with Thousand Oaks resident Tyler Kelly at the helm. Tucked safely into a car seat in the back was 2-year-old Pierce Kelly, known by family and friends as Fierce Pierce, still recovering from a July 21 bone marrow transplant.

At the La Caada home of relatives Donna and Dave McLaughlin, Pierce will recuperate under the watchful eye of mom Aubrey. For 100 days following the procedure, he must reside within a 30-minute drive of Childrens Hospital for monitoring.

Saturdays 13-mile drive was just one portion of a tumultuous journey the Kellys have been on since April 7, when Pierce was diagnosed with acute myeloid leukemia. His chance of surviving the devastating illness with treatment alone was only 50%, according to mom Aubrey. But there was one hope if the Kellys could find a bone marrow donor, Pierces odds would improve by at least another 15%.

We were at the mercy of whoever had registered, Aubrey Kelly recalled.

Among the nearly 13.5 million Americans already listed as donors on the Be the Match Marrow Registry, there were no donors close enough to be a match with Pierce.

Raquel Edpao, a community outreach specialist for Be the Match, said on any given day there are 14,000 people like the Kellys, searching registries for a bone marrow match. Its her job to help educate people how simple it is to join the registry and to donate if called.

Potential donors register online at bethematch.org, then receive and turn in a cheek swab. After that, theyre contacted if they are a potential match for someone. Edpao estimates about one out of every 430 registrants will be asked to donate.

There are so many misconceptions about donating, she said, invoking myths about spinal drilling, painful extractions and missed days at work. Its usually as simple as donating blood.

In about 20% of cases donors are asked to undergo a marrow extraction, a 45-minute outpatient procedure involving a general anesthetic.

Luckily for the Kellys, a search of donors worldwide returned a single donor in France whose human leukocyte antigen (HLA) protein was a 10-out-of-10 match with Pierces. While the marrow was shipped, the 2-year-old underwent chemotherapy to destroy most of his damaged stem cells in preparation for the donation.

Its a fine balance of leaving him with enough cells to receive the new ones, but not so many that the new cells dont have enough room to grow, Aubrey Kelly said, explaining how her sons blood type switched from A positive, his own type, to the donors O negative.

Pierces recovery from the transplant requires a sterile environment that means he cannot stay with siblings Sierra, 4, and 6-month-old Harper. Donna McLaughlin, a cousin of Aubrey Kellys dad, said she and husband Dave were happy to offer their home in La Caadas Paradise Valley neighborhood for his recovery.

Ive worked for the past week cleaning my house its never been so clean, she said of her preparation for Pierce and Aubreys 57-day visit. Im being paranoid, I know, but he is going to be OK on my watch.

Knowing he would have to return to Thousand Oaks to take care of Pierces sisters, Tyler Kelly wanted to ensure his sons trip from the hospital would be a special one. The Bronco the same vehicle his mother drove to the hospital in 1981 so he could be delivered, and the same one he and Aubrey have used to get to the delivery room in time for the birth of their own three children seemed a fitting conveyance.

We wanted to continue the tradition, he said.

Hoping to assemble a retinue for the drive, Tyler Kelly reached out to enthusiast club SoCal Broncos and classicbroncos.com. Several people responded, including Agoura Hills Bronco owner Dan Bennett, for whom the cause was personal. About 10 years ago he saved a life by donating his own bone marrow.

To be able to go in and help play an intrinsic role in saving someones life is a really special thing, Bennett said. I think everybody should do it.

sara.cardine@latimes.com

Twitter: @SaraCardine

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September 8th, 2017

Decatur elementary student gets stem cells from mother – The Decatur Daily

By Sykes24Tracey

A Decatur elementary student and her mother are recovering following a stem cell transplant in a Cincinnati-area hospital.

It will be six to eight weeks, however, before doctors know whether the membrane Nicole Richey gave her daughter Phoenix is working.

What were praying for is that Phoenix will start producing her own stem cells, Joey Richey said by telephone Thursday.

In January, Phoenix, a fourth-grade student at Chestnut Grove Elementary, was diagnosed with Stevens-Johnsons syndrome, a rare and serious disorder of the skins mucous membranes.

According to the Mayor Clinic, the syndrome is caused by a reaction to medication or infection and begins with flu-like symptoms, which Phoenix had. The disease is followed by painful rashes and blisters that ultimately cause the top layer of skin to die.

The disease affected between 60 and 65 percent of Phoenixs body and damaged her eyes.

During the outpatient procedure, which is called a limbal stem cell transplant, said Joey Richey, surgeons took about 40 percent of the cornea from his wifes left eye and placed it in Phoenixs right eye.

Nicole Richey said she was close to a perfect match, but doctors have put her daughter on immunosuppression therapy to lower the possibility of Phoenix rejecting the stem cells.

I am still having a hard time after my surgery, but were OK, Nicole Richey said.

The procedure took place at St. Elizabeth North Kentucky Surgical Center, and Phoenix will miss about six weeks of school.

Chestnut Grove Principal Luke Bergeson said Phoenix will continue to receive homebound instructional services until she is ready to return to school.

Phoenixs body is still not able to grow its own skin, so she has been fitted with a prokera ring, which is a therapeutic device to protect her eyes. Her left eye is temporarily sewn shut and will be until doctors see how the right eye reacts to the transplant, Joey Richey said.

They are working on one eye at a time, he said.

Phoenix was diagnosed with Stevens-Johnsons syndrome while she was out of school on Christmas break last year. The outer layer of skin started to die and was peeling two days before she was admitted to Huntsville Hospital. On Jan. 12, doctors transferred Phoenix to the burn unit at Childrens Hospital of Birmingham for treatment.

She stayed there a week before being moved to Shriners Hospital for Children in Cincinnati, where she stayed until Feb. 8.

Phoenix missed the remainder of the school term, but she came back to Chestnut Grove when classes started in August.

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September 8th, 2017

‘Nanotransfection’ Turns Animal Skin into Blood Vessels and Brain Cells – Medical Device and Diagnostics Industry

By Sykes24Tracey

Nancy Crotti

Researchers have developed tissue nanotransfection, a process for regrowing tissue inside the human body.

Researchers at Ohio State University have developed breakthrough stem cell technology that can regrow tissue inside the human body, rather than in a laboratory.

Their work has implications for critical limb ischemia, brain disorders, and possibly even organ engineering and bone regrowth, according to Chandan Sen, PhD, director of the Center for Regenerative Medicine and Cell-Based Therapies at Ohio State's Wexner Medical Center in Columbus. Sen led the team that developed the technology.

Here's how the process, known as nanotransfection, works: The scientists make synthetic RNA and DNA to match that of the patient. They load it into nanochannels inside tiny needles embedded in a chip and apply the chip to the skin. The needles electrocute about 2% of the cell surface with the patient's nucleic acid. The procedure takes 1/10th of a second, and has been shown to work with up to 98% efficiency.

In experiments on mice, the technology restored blood flow to injured legs by reprogramming the animals' skin cells to become vascular cells. With no other form of treatment, active blood vessels had formed within two weeks, and by the third week, blood flow returned and the legs of the mice were saved.

The researchers also induced strokes in mice and used the chips to grow new brain tissue from the animals' skin and transplant it to their brains. Bodily function damaged by the strokes was restored. The study of the technique, which worked with up to 98% efficiency, was reported in the journal Nature Nanotechnology.

The technology marks an advance over cell regeneration conducted in a laboratory, because those cells mostly underperform or die once transplanted into the body, according to Sen. The researchers use skin cells in their work because, as Sen explained, everybody has some to spare.

"We grow it in you and we move it over to the organ so you have your own cells populating your organ," he said. "It's all coming from you."

The synthetic RNA and DNA reprogram cells in the same way that fetal cells develop different functions to become different body parts, Sen added. The researchers worked on the technology for more than four years, also conducting successful blood flow restoration experiments on pigs. When they begin human trials, their first patients will likely be those whose critical limb ischemic has reached the stage where amputation is the only option.

The scientists' work has generated interest in Europe, Asia, the Middle East, and in the United States. Ohio State will decide where to pursue human trials first, and is searching for industry partners.

"The cost is extremely low and complexity-wise it is extremely low. I see very little barrier to take it to humans," Sen said.

The researchers' work marks another interface between silicon chips and biology. Other applications picked up by manufacturers include DNA sequencing machines, miniaturized diagnostic tests using disposable photonic chips, accurate body monitoring sensors, and brain stimulation probes.

Sen and his team acknowledge that their work will be met with skepticism.

"Whenever you do something that is sort of transformative, you will expect that," Sen said. "Therefore, we actually published this in the most rigorous journal possible. We went through 16 months of criticism and response, after which this was published."

Nancy Crotti is a freelance contributor to MD+DI.

[Image courtesy of THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER]

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September 8th, 2017

Stem Cell Factor Tied to Reduced Risk of Cardiac Events, Death – Anti Aging News

By Sykes24Tracey

High levels of stem cell factor (SCF) are associated with reduced risk of mortality and cardiovascular events, according to a study published online Aug. 26 in theJournal of Internal Medicine.

(HealthDay News) -- High levels of stem cell factor (SCF) are associated with reduced risk of mortality and cardiovascular events, according to a study published online Aug. 26 in theJournal of Internal Medicine.

Harry Bjrkbacka, Ph.D., from Lund University in Sweden, and colleagues examined the correlation between circulating levels of SCF and risk for development of cardiovascular events and death. SCF was analyzed from plasma from 4,742 participants in the Malm Diet and Cancer Study; participants were followed for a mean of 19.2 years.

The researchers found that participants with high baseline levels of SCF had lower cardiovascular and all-cause mortality and reduced risk of heart failure, stroke, and myocardial infarction. There was a correlation for smoking, diabetes, and high alcohol consumption with lower levels of SCF. After adjustment for traditional cardiovascular risk factors, the highest versus the lowest SCF quartile remained independently associated with lower risk of cardiovascular (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81) and all-cause mortality (hazard ratio, 0.68; 95 percent confidence interval, 0.57 to 0.81) and with lower risk of heart failure (hazard ratio, 0.5; 95 percent confidence interval, 0.31 to 0.8) and stroke (hazard ratio, 0.66; 95 percent confidence interval, 0.47 to 0.92) but not myocardial infarction (hazard ratio, 0.96; 95 percent confidence interval, 0.72 to 1.27).

"The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity," the authors write.

The possibilities that stem cell therapies present in the prevention, regeneration, and treatment of many health conditions seem to be still untouched. If course, stem cell research is still ongoing and no one is complete stem cell expert yet, but maybe thats a good approach to take. I am not so sure I would be comfortable in this modern area of easily accessible information with a physician that still doesnt consider his or her self a student. Whether your doctor is 65 or 38 I hope they are still open to learning, stated Dr. Ronald Klatz, President of the A4M.

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September 8th, 2017

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Stem cells for stenosis – Dr. Marc Darrow is a Stem Cell …

By Sykes24Tracey

stem cell | Definition, Types, Uses, Research, & Facts …

By Sykes24Tracey

Adult Cardiac Stem Cells Don’t Exist: Study | The …

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Mending a Broken Heart: Stem Cells and Cardiac Repair …

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Next Steps for Cardiac Stem Cells – MedStar Heart …

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Press Releases Viacyte, Inc.

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Stem Cell Treatments – Brain and Spinal Cord

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What is a Stem Cell Transplant (Bone Marrow Transplant)? | Cancer.Net

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Bone marrow | anatomy | Britannica.com

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Stories of Hope: Spinal Cord Injury | California’s Stem …

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Regeneration of the entire human skin using transgenic …

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Fully Functional Skin Grown From Stem Cells Could Double …

By Sykes24Tracey

What are stem cells and how will they be used to treat the …

By Sykes24Tracey

Stem Cell-Based Therapy for Cartilage Regeneration and …

By Sykes24Tracey

Heart Failure and Transplant Program New Jersey

By Sykes24Tracey

Skin Stem Cells – Methods and Protocols | Kursad Turksen …

By Sykes24Tracey

Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

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Decatur elementary student gets stem cells from mother – The Decatur Daily

By Sykes24Tracey

‘Nanotransfection’ Turns Animal Skin into Blood Vessels and Brain Cells – Medical Device and Diagnostics Industry

By Sykes24Tracey

Stem Cell Factor Tied to Reduced Risk of Cardiac Events, Death – Anti Aging News

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