Regenerating heart tissue through stem cell … – Mayo Clinic

Volume 9, Issue 1 Summary

A groundbreaking study on repairing damaged heart tissue through stem cell therapy has given patients hope that they may again live active lives. An international team of Mayo Clinic researchers and collaborators has done it by discovering a way to regenerate heart tissue.

Clinical trial participant Miroslav Dlacic near his home in Belgrade.

Andre Terzic, M.D., Ph.D., is the Michael S. and Mary Sue Shannon Family Director, Center for Regenerative Medicine, and the Marriott Family Professor of Cardiovascular Diseases Research at Mayo Clinic in Minnesota.

Miroslav Dlacic's heart attack changed his life drastically and seemingly forever. His damaged heart made him too tired to work in his garden or to spend much time at his leather-accessories workshop in Belgrade, Serbia. Like many patients with heart problems, Dlacic, who is 71, thought he would live his remaining years in a weakened condition.

Then, a groundbreaking Mayo Clinic trial of stem cell therapy to repair damaged heart tissue changed his life again this time for the better.

Dlacic agreed to participate in the Mayo Clinic stem cell trial through the hospital in Serbia where he is treated. Two years later, Dlacic is able to walk again without becoming worn out.

"I am more active, more peppy," he says. "I feel quite well."

"It's a paradigm shift," says Andre Terzic, M.D., Ph.D., director of Mayo Clinic's Center for Regenerative Medicine and senior investigator of the stem cell trial. "We are moving from traditional medicine, which addresses the symptoms of disease, to being legitimately able to cure disease."

For decades, treating patients with cardiac disease has typically involved managing heart damage with medication. It's a bit like driving a car without fixing a sluggish engine you manage the consequences as best you can and learn to live with them.

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Regenerating heart tissue through stem cell ... - Mayo Clinic

Somatic cell – Wikipedia, the free encyclopedia

A somatic (Greek: /soma = body) or vegetative cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell.[1]

In contrast, gametes are cells that fuse during sexual reproduction, germ cells are cells that give rise to gametes, and stem cells are cells that can divide through mitosis and differentiate into diverse specialized cell types. For example, in mammals, somatic cells make up all the internal organs, skin, bones, blood and connective tissue, while mammalian germ cells give rise to spermatozoa and ova which fuse during fertilization to produce a cell called a zygote, which divides and differentiates into the cells of an embryo. There are approximately 220 types of somatic cells in the human body.[1]

The word "somatic" is derived from the Greek word sma, meaning "body".

As multicellularity evolved many times, sterile somatic cells did too. The evolution of an immortal germline producing specialized somatic cells involved the emergence of mortality, and can be viewed in its simplest version in volvocine algae.[2] Those species with a separation between sterile somatic cells and a germ line are called Weismannists. However, Weismannist development is relatively rare (e.g., vertebrates, arthropods, Volvox), as great part of species have the capacity for somatic embryogenesis (e.g., land plants, most algae, many invertebrates).[3][4]

Like all cells, somatic cells contain DNA arranged in chromosomes. If a somatic cell contains chromosomes arranged in pairs, it is called diploid and the organism is called a diploid organism. (The gametes of diploid organisms contain only single unpaired chromosomes and are called haploid.) Each pair of chromosomes comprises one chromosome inherited from the father and one inherited from the mother. For example, in humans, somatic cells contain 46 chromosomes organized into 23 pairs. By contrast, gametes of diploid organisms contain only half as many chromosomes. In humans, this is 23 unpaired chromosomes. When two gametes (i.e. a spermatozoon and an ovum) meet during conception, they fuse together, creating a zygote. Due to the fusion of the two gametes, a human zygote contains 46 chromosomes (i.e. 23 pairs).

However, a large number of species have the chromosomes in their somatic cells arranged in fours ("tetraploid") or even sixes ("hexaploid"). Thus, they can have diploid or even triploid germline cells. An example of this is the modern cultivated species of wheat, Triticum aestivum L., a hexaploid species whose somatic cells contain six copies of every chromatid.

In recent years, the technique of cloning whole organisms has been developed in mammals, allowing almost identical genetic clones of an animal to be produced. One method of doing this is called "somatic cell nuclear transfer" and involves removing the nucleus from a somatic cell, usually a skin cell. This nucleus contains all of the genetic information needed to produce the organism it was removed from. This nucleus is then injected into an ovum of the same species which has had its own genetic material removed. The ovum now no longer needs to be fertilized, because it contains the correct amount of genetic material (a diploid number of chromosomes). In theory, the ovum can be implanted into the uterus of a same-species animal and allowed to develop. The resulting animal will be a nearly genetically identical clone to the animal from which the nucleus was taken. The only difference is caused by any mitochondrial DNA that is retained in the ovum, which is different from the cell that donated the nucleus. In practice, this technique has so far been problematic, although there have been a few high profile successes, such as Dolly the Sheep and, more recently, Snuppy, the first cloned dog.

Development of Biotechnology has allowed for the genetic manipulation of somatic cells.This biotechnology deals with some ethical controversy in Human genetic engineering.

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Somatic cell - Wikipedia, the free encyclopedia

Adult Non-Hodgkin Lymphoma Treatment – National Cancer …

General Information About Adult Non-Hodgkin Lymphoma (NHL)

The NHLs are a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment.[1]

Like Hodgkin lymphoma, NHL usually originates in lymphoid tissues and can spread to other organs. NHL, however, is much less predictable than Hodgkin lymphoma and has a far greater predilection to disseminate to extranodal sites. The prognosis depends on the histologic type, stage, and treatment.

Estimated new cases and deaths from NHL in the United States in 2015:[2]

NHL usually originates in lymphoid tissues.

Anatomy of the lymph system.

The NHLs can be divided into two prognostic groups: the indolent lymphomas and the aggressive lymphomas.

Indolent NHL types have a relatively good prognosis with a median survival as long as 20 years, but they usually are not curable in advanced clinical stages.[3] Early-stage (stage I and stage II) indolent NHL can be effectively treated with radiation therapy alone. Most of the indolent types are nodular (or follicular) in morphology.

The aggressive type of NHL has a shorter natural history, but a significant number of these patients can be cured with intensive combination chemotherapy regimens.

In general, with modern treatment of patients with NHL, overall survival at 5 years is over 60%. Of patients with aggressive NHL, more than 50% can be cured. The vast majority of relapses occur in the first 2 years after therapy. The risk of late relapse is higher in patients who manifest both indolent and aggressive histologies.[4]

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Adult Non-Hodgkin Lymphoma Treatment - National Cancer ...

Platelet-Rich Plasma (PRP) Injections – HSS.edu – HSS

see also Injections

Platelet activation plays a key role in the process of wound and soft tissue healing. The use of platelet rich plasma (PRP), a portion of the patients own blood having a platelet concentration above baseline, to promote healing of injured tendons, ligaments, muscles, and joints, can be applied to various musculoskeletal problems.

Ultrasound and photograph of a PRP injection into a patient's tendon tear.

It was used as early as the 1990s in maxillo-facial and plastic surgery. PRP injections are prepared from one to a few tubes of the patients own blood with strict aseptic technique. After being centrifuged, the activated platelets are injected into the abnormal tissue, releasing growth factors that recruit and increase the proliferation of reparative cells. Ultrasound imaging may or may not be used to guide the injection.

Several clinical studies have demonstrated that PRP injections have improved function and decreased pain to various maladies, including - but not limited to - elbow, wrist, shoulder, hip, knee, and ankle tendonosis. Early work is also showing promise for osteoarthritis.

The side effects of PRP injections are very limited as the patient is utilizing their own blood, which they should have no reaction to. Some relative rest is needed immediately following the procedure, then usually followed by a progressive stretching and strengthening program.

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Platelet-Rich Plasma (PRP) Injections - HSS.edu - HSS

Non-Small Cell Lung Cancer Treatment – National Cancer …

General Information About Non-Small Cell Lung Cancer (NSCLC)

NSCLC is any type of epithelial lung cancer other than small cell lung cancer (SCLC). The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants. Although NSCLCs are associated with cigarette smoke, adenocarcinomas may be found in patients who have never smoked. As a class, NSCLCs are relatively insensitive to chemotherapy and radiation therapy compared with SCLC. Patients with resectable disease may be cured by surgery or surgery followed by chemotherapy. Local control can be achieved with radiation therapy in a large number of patients with unresectable disease, but cure is seen only in a small number of patients. Patients with locally advanced unresectable disease may achieve long-term survival with radiation therapy combined with chemotherapy. Patients with advanced metastatic disease may achieve improved survival and palliation of symptoms with chemotherapy, targeted agents, and other supportive measures.

Estimated new cases and deaths from lung cancer (NSCLC and SCLC combined) in the United States in 2014:[1]

Lung cancer is the leading cause of cancer-related mortality in the United States.[1] The 5-year relative survival rate from 1995 to 2001 for patients with lung cancer was 15.7%. The 5-year relative survival rate varies markedly depending on the stage at diagnosis, from 49% to 16% to 2% for patients with local, regional, and distant stage disease, respectively.[2]

NSCLC arises from the epithelial cells of the lung of the central bronchi to terminal alveoli. The histological type of NSCLC correlates with site of origin, reflecting the variation in respiratory tract epithelium of the bronchi to alveoli. Squamous cell carcinoma usually starts near a central bronchus. Adenocarcinoma and bronchioloalveolar carcinoma usually originate in peripheral lung tissue.

Anatomy of the respiratory system.

Smoking-related lung carcinogenesis is a multistep process. Squamous cell carcinoma and adenocarcinoma have defined premalignant precursor lesions. Before becoming invasive, lung epithelium may undergo morphological changes that include the following:

Dysplasia and carcinoma in situ are considered the principal premalignant lesions because they are more likely to progress to invasive cancer and less likely to spontaneously regress.

In addition, after resection of a lung cancer, there is a 1% to 2% risk per patient per year that a second lung cancer will occur.[3]

NSCLC is a heterogeneous aggregate of histologies. The most common histologies include the following:

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Non-Small Cell Lung Cancer Treatment - National Cancer ...

Non-small cell lung cancer | University of Maryland …

Description

An in-depth report on the causes, diagnosis, treatment, and prevention of non-small cell lung cancer (NSCLC).

Lung cancer - non-small cell; NSCLC

Risk:

Treatment:

Although lung cancer accounts for only 15% of all newly-diagnosed cancers in the United States, it is the leading cause of cancer death in U.S. men and women. It is more deadly than colon, breast, and prostate cancers combined. About 160,000 patients die from lung cancer each year. Death rates have been declining in men over the past decade, and they have about stabilized in women.

The lungs are two spongy organs surrounded by a thin moist membrane called the pleura. Each lung is composed of smooth, shiny lobes: the right lung has three lobes, and the left has two. About 90% of the lung is filled with air. Only 10% is solid tissue.

The major features of the lungs include the bronchi, the bronchioles, and the alveoli. The alveoli are the microscopic blood vessel-lined sacks in which oxygen and carbon dioxide gas are exchanged.

Lung cancer develops when genetic mutations (changes) occur in a normal cell within the lung. As a result, the cell becomes abnormal in shape and behavior, and reproduces endlessly. The abnormal cells form a tumor that, if not surgically removed, invades neighboring blood vessels and lymph nodes and spreads to nearby sites. Eventually, the cancer can spread (metastasize) to locations throughout the body.

The two major categories of lung cancer are small cell lung cancer and non-small cell lung cancer. Most lung cancers are non-small cell cancer, the subject of this report. Less common cancers of the lung are known as carcinoids, cylindromas, and certain sarcomas (cancer in soft tissues). Some experts believe all primary lung cancers come from a single common cancerous (malignant) stem cell. As it copies itself, that stem cell can develop into any one of these cancer types in different people.

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Non-small cell lung cancer | University of Maryland ...

Stem Cell Research Facts – Adult Stem Cell Success

"I Will Walk Again" The Laura Dominguez Story If there was ever a woman on a mission, its Laura Dominguez. Doctors once told her shed never walk again. And while shes not ready to run a marathon, shes already proving them wrong, with the best yet to come.

An oil spill on a San Antonio freeway is blamed for the car crash that sent Laura and her brother directly into a retaining wall one summer afternoon in 2001. Laura was just 16 years old at the time and the crash left her completely paralyzed from the neck down. Surgeons say she suffered whats known as a C6 vertebrae fracture that severely damaged her spinal cord.

I refused to accept their prognosis that I never would walk again and began searching for other options, says Laura. After stays in several hospitals for nearly a year, Laura and her mother relocated to San Diego, CA so that she could undergo extensive physical therapy. While in California, they met a family whose daughter was suffering from a similar spinal cord injury. They were also looking for other alternatives to deal with spinal cord injuries.

After extensive research and consultations with medical experts in the field of spinal cord injuries, they decided to explore a groundbreaking new surgical procedure using adult stem cells pioneered by Dr. Carlos Lima of Portugal.

The surgery involved the removal of tissue from the olfactory sinus area at the back of the nose--and transplanting it into the spinal cord at the injury site. Both procedures, the harvesting of the tissue and the transplant, were done at the same time. Laura was the tenth person in the world and the second American to have this procedure done and was featured in a special report by PBS called Miracle Cell. (Link to Miracle Cell (PBS) Episode)

Following the surgery she returned to California where she continued with the physical therapy regimen, then eventually returned home to San Antonio. Upon her return home, an MRI revealed her spinal cord was beginning to heal. Approximately 70% of the lesion now looked like normal spinal cord tissue. More importantly to Laura, she began to regain feeling in parts of her upper body and within six months of the surgery regained feeling down to her abdomen.

Improvements in sensory feelings have continued until the present time. She can feel down to her hips, and has regained feeling and some movement in her legs. Lauras upper body has gained more strength and balance and one of the most evident improvements has been her ability to stand and remain standing, using a walker, and with minimal assistance. When she stands she can contract her quadriceps and hamstring muscles.

Every week it seems Im able to do something new, something different that I hadnt done the week before, says Laura.

Now Lauras story is poised to take a new, potentially groundbreaking turn. In the Fall of 2009, she traveled again to Portugal where adult stem cells were extracted from her nose for culturing. As this story is written, she is preparing to fly back to Portugal where scar tissue at her injury site will be removed and her own adult stem cells injected in the area of her original wound.

The Laura Dominguez story is not complete. The next chapter may or may not yield the results she seeksbut no one can deny the determination and courage of Laura. For her part, she has one goal in mind: I will walk again.

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Stem Cell Research Facts - Adult Stem Cell Success

Generating Mice from Induced Pluripotent Stem Cells | Protocol

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JoVE Biology

Michael J. Boland1, Jennifer L. Hazen1, Kristopher L. Nazor1, Alberto R. Rodriguez2, Greg Martin2, Sergey Kupriyanov2, Kristin K. Baldwin1

1Dorris Neuroscience Center & Department of Cell Biology, The Scripps Research Institute, 2Mouse Genetics Core Facility, The Scripps Research Institute

Generating induced pluripotent stem cell (iPSC) lines produces lines of differing developmental potential even when they pass standard tests for pluripotency. Here we describe a protocol to produce mice derived entirely from iPSCs, which defines the iPSC lines as possessing full pluripotency1.

Date Published: 11/29/2012, Issue 69; doi: 10.3791/4003

Keywords: Stem Cell Biology, Issue 69, Molecular Biology, Developmental Biology, Medicine, Cellular Biology, Induced pluripotent stem cells, iPSC, stem cells, reprogramming, developmental potential, tetraploid embryo complementation, mouse

Boland, M. J., Hazen, J. L., Nazor, K. L., Rodriguez, A. R., Martin, G., Kupriyanov, S., et al. Generation of Mice Derived from Induced Pluripotent Stem Cells. J. Vis. Exp. (69), e4003, doi:10.3791/4003 (2012).

The production of induced pluripotent stem cells (iPSCs) from somatic cells provides a means to create valuable tools for basic research and may also produce a source of patient-matched cells for regenerative therapies. iPSCs may be generated using multiple protocols and derived from multiple cell sources. Once generated, iPSCs are tested using a variety of assays including immunostaining for pluripotency markers, generation of three germ layers in embryoid bodies and teratomas, comparisons of gene expression with embryonic stem cells (ESCs) and production of chimeric mice with or without germline contribution2. Importantly, iPSC lines that pass these tests still vary in their capacity to produce different differentiated cell types2. This has made it difficult to establish which iPSC derivation protocols, donor cell sources or selection methods are most useful for different applications.

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Generating Mice from Induced Pluripotent Stem Cells | Protocol

induced pluripotent stem cells – RCN Corporation

Stem cells are cells that divide by mitosis to form either

How the choice is made is still unknown. However, several genes have been found whose activity prevents a daughter cell from differentiating.

The only totipotent cells are the fertilized egg and the first 4 or so cells produced by its cleavage (as shown by the ability of mammals to produce identical twins, triplets, etc.).

In mammals, the expression totipotent stem cells is a misnomer totipotent cells cannot make more of themselves.

Three types of pluripotent stem cells occur naturally:

All three of these types of pluripotent stem cells

In mice and rats, embryonic stem cells can also:

Using genetic manipulation in the laboratory, pluripotent stem cells can now be generated from differentiated cells. These induced pluripotent stem cells (iPSCs) are described below.

Multipotent stem cells are found in adult animals; perhaps most organs in the body (e.g., brain, liver, lungs) contain them where they can replace dead or damaged cells. These adult stem cells may also be the cells that when one accumulates sufficient mutations produce a clone of cancer cells.

Examples:

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induced pluripotent stem cells - RCN Corporation

Adult Stem Cells 101 | Boston Children’s Hospital

Although commonly used and accepted, the term "adult stem cells" is a little misleading, since these cells are actually found in infants and children as well as in adults. Adult stem cells produce the different kinds of cells that maintain the bodys tissues and organs, and, importantly, they have the ability to divide and reproduce indefinitely. These cells typically produce the type of tissue in which they are found. Adult stem cells are sometimes also called somatic stem cells.

Various types of adult stem cells have been identified in many organs and tissues. They range from cells that are able to form many different kinds of tissues to more specialized cells that form just some of the cells of a particular tissue or organ. Mesenchymal stem cells, for example, are adult stem cells that form fat cells, cartilage, bone, tendon, ligaments, muscle cells, skin cells and even nerve cells. In contrast, hematopoietic stem cells give rise to blood cells only (red cells, white cells and platelets), while neural stem cells form only cells in the nervous system.

Often confused with adult stem cell, progenitor cells are early descendants of stem cells that can differentiate to form one or more kinds of cells, but cannot divide and reproduce indefinitely.

Some tissues and organs have more adult stem cells than others. Those organs with fewer or no stem cells (the heart, for example) dont readily regenerate when they are injured or diseased.

Scientists around the world are actively studying ways to isolate different kinds of adult stem cells, to control and expand the rate at which they make copies of themselves, and to learn how to direct them to form the specific cell types needed for treatment.

Learn more about adult stem cells by clicking on these links:

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Adult Stem Cells 101 | Boston Children's Hospital