A new method for delivering stem cells to damaged heart muscle has shown early promise in treating severe heart failure, researchers report.

In a preliminary study, they found the tactic was safe and feasible for the 48 heart failure patients they treated. And after a year, the patients showed a modest improvement in the heart's pumping ability, on average.

It's not clear yet whether those improvements could be meaningful, said lead researcher Dr. Amit Patel, director of cardiovascular regenerative medicine at the University of Utah.

He said larger clinical trials are underway to see whether the approach could be an option for advanced heart failure.

Other experts stressed the bigger picture: Researchers have long studied stem cells as a potential therapy for heart failure -- with limited success so far.

"There's been a lot of promise, but not much of a clinical benefit yet," said Dr. Lee Goldberg, who specializes in treating heart failure at the University of Pennsylvania.

Researchers are still sorting through complicated questions, including how to best get stem cells to damaged heart muscle, said Goldberg, who was not involved in the new study.

What's "novel" in this research, he said, is the technique Patel's team used to deliver stem cells to the heart. They took stem cells from patients' bone marrow and infused them into the heart through a large vein called the coronary sinus.

Patel agreed that the technique is the advance.

"Most other techniques have infused stem cells through the arteries," Patel explained. One obstacle, he said, is that people with heart failure generally have hardened, narrowed coronary arteries, and the infused stem cells "don't always go to where they should."

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Stem Cells Show Promise in Heart Failure Treatment

Clara's Story

Clara had a severe heart attack in 2004. Before contacting us she had received adult stem cells from a company in Thailand - a process requiring at least a one week stay.

When she contacted Stemaid, she had just had an echocardiogram showing that her overall left ventricular ejection fraction was estimated to be 30 to 35%. She opted to receive one injection of 5 million Embryonic Stem Cells by Stemaid in November 2010. She arrived at 1pm and was done by 3pm the same day.

We received the following email from her in April 2011: I had an EKO last week and rate is 44%, up from the 33/35% it was before I received Stemaid's stem cells! . Are the stem cells still available and still as good?

The heart contains a small amount of stem cells, the cardiac stem cells, that are produced when there is a need for production of more heart cells or for an active replacement of damaged ones. These cardiac cells are produced in high quantity for about one week following an infarction, actively repairing the damaged areas of the heart.

However this high production stops after a week and the repair stops as well.

Initial studies showed that by introducing embryonic stem cells, the heart starts to repair again within minutes of their injection. More recent studies showed that the injection of embryonic stem cells actually triggers the production of cardiac stem cells for one week. Another week of active repair is offered each time that one receives embryonic stem cells.

If you have suffered from an infarction, we suggest a minimum of 3 injections of esc over the course of 3 weeks to get significant repair.

Some of the patients who have received Stemaid Embryonic Stem-Cells have agreed to be mentioned on our website so that we may illustrate the benefits of them.

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Heart Disease - Stemaid : Embryonic Stem-cells

Date: 01 Aug 2015

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Tanshinone IIA (TSA) is a lipophilic diterpene purified from the Chinese herb Danshen, which exhibits potent antioxidant and anti-inflammatory properties. Effect of TSA remains largely uninvestigated on the osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), which are widely used in cell-based therapy of bone diseases. In the present study, both ALP activity at day 7 and calcium content at day 24 were upregulated during the osteogenesis of mouse BM-MSCs treated with TSA (1 and 5M), demonstrating that it promoted the osteogenesis at both early and late stages. We found that TSA promoted osteogenesis and inhibited osteoclastogenesis, evident by RT-PCR analysis of osteogenic marker gene expressions. However, osteogenesis was inhibited by TSA at 20M. We further revealed that TSA (1 and 5M) upregulated BMP and Wnt signaling. Co-treatment with Wnt inhibitor DKK-1 or BMP inhibitor noggin significantly decreased the TSA-promoted osteogenesis, indicating that upregulation of BMP and Wnt signaling plays a significant role and contributes to the TSA-promoted osteogenesis. Of clinical interest, our study suggests TSA as a promising therapeutic strategy during implantation of BM-MSCs for a more effective treatment of bone diseases.

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Effects of Tanshinone IIA on osteogenic differentiation of ...

Our skin has the amazing capability to renew itself throughout our adult life. Also, our hair follicle goes through a cycle of growth and degeneration. This happens all the time in our skin even though we are not aware of it. However, even though skin renews itself we still have to help it a little bit to get better results. Stem cells play an important role in this process of skin renewal or hair growth and the purpose of this article is to discuss and provide additional information about these tiny cells that play a big part in our life.

Skin stem cell is defined as multipotent adult skin cells which are able to self-renew or differentiate into various cell lineages of the skin. These cells are active throughout our life via skin renewal process or during skin repair after injuries. These cells reside in the epidermis and hair follicle and one of their purposes is to ensure the maintenance of adult skin and hair regeneration.

The truth is, without these little cells, our skin wouldnt be able to cope with various environmental influences. Our skin is exposed to different influences 24/7, for example, washing your face with soap, going out during summer or cold winter days etc. All these factors have a big impact on our skin and it constantly has to renew itself to stay in a good condition. This is where skin stem cells step in. They make sure your skin survives the influence of constant stress, heat, cold, even makeup, soap, etc.

Our skin is quite sensitive and due to its constant exposure to different influences throughout the day, it can get easily damage. Damage to skin cells can be caused by pretty much everything, from soap to cigarette smoke. One of the most frequent skin cell damages are the result of:

Skin stem cells are still subjected to scientific projects where researchers are trying to discover as much as possible about them. So far, they have identified several types of these cells, and they are:

Also, some scientists suggest that there is another type of stem cells mesenchymal stem cells which can be found in dermis (layer situated below the epidermis) and hypodermis (innermost and the thickest layer of the skin). However, this claim has been branded controversial and is a subject of many arguments and disputes between scientists. It is needed to conduct more experiments to find out whether this statement really is true.

Stem cells are found in many organs and tissues, besides skin. For example, scientists have discovered stem sells in brain, heart, bone marrow, peripheral blood, skeletal muscle, teeth, liver, gut etc. Stem cells reside in a specific area of each tissue or organ and that area is called stem cell niche. The same case is with the skin as well.

The ability of stem cells to regenerate and form almost any cell type in the body inspired scientists to work on various skin products that contain stem cells. Also, they decided to investigate the effect of plant stem cells on human skin. They discovered that plant stem cells are, actually, very similar to human skin stem cells and they function in a similar way as well. This discovery made scientists turn to plants as the source of stem cells and are trying to include them into the skin products due to their effectiveness in supporting skins cellular turnover. Another similarity between plant stem cells and human skin stem cells is their ability to develop according to their environment.

Fun Fact: The inspiration to use plant stem cells in skin care came from an unusual place almost extinct apple tree from Switzerland.

The benefits of plant stem cells on human skin are versatile. They offer possibility to treat some skin conditions, heal wounds, and repair the skin after some injury faster than it would usually take. Also, they bring back elasticity to the skin, reduce the appearance of wrinkles and slow down the aging process.

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Skin Stem Cells: Benefits, Types, Medical Applications and ...

You will have a low white blood cell count after your treatment. This means you are more at risk of getting an infection. You are likely to get an infection from the normally harmless bacteria we all have in our digestive systems and on our skin.

To stop this from happening your nurse may give you tablets called gut sterilisers (antibiotics) and mouthwashes. And they will encourage you to have a shower each day.

You are also at risk of infection from food. The nurses on the ward will tell you and your relatives about the food you can and can't eat. The rules vary from hospital to hospital but you may be told that

Your room will be thoroughly cleaned every day. Your visitors will be asked to wash their hands before they come into your room. They may also have to wear disposable gloves and aprons. Visitors with coughs and colds are not allowed. Some hospitals don't allow you to have plants or flowers in your room because bacteria and fungi can grow in the soil or water, and may cause infection.

Even with all these precautions, most people do get an infection at some point and need to have antibiotics. You can help yourself by trying to do your mouth care properly and getting up to shower and have your bed changed even on the days you don't feel too good.

After a transplant you will have lost immunity to diseases you were vaccinated against as a child. The team caring for you will advise you about the immunisations you need and when. You should only have inactivated immunisations and not live ones. To lower the risk of you getting any of these infections it is important that all your family have the flu vaccine and any children have all their immunisations.

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Side effects of bone marrow and stem cell transplants ...

Hair follicle lineage and niche signals regulate hair follicle stem cells. (a) HFSCs can exist in two states. Quiescent bulge stem cells (Bu-SCs) are located in the outer layer of this niche and contribute to the generation of the outer root sheath. Primed stem cells reside in the hair germ, sandwiched between the bulge and a specialized dermal cluster known as the dermal papilla. They are responsible for generating the transit amplifying cell (TAC) matrix, which then gives rise to the hair shaft and its inner root sheath (IRS) channel. Although matrix and IRS are destroyed during catagen, many of the outer root sheath (ORS) cells are spared and generate a new bulge right next to the original one at the end of catagen. The upper ORS contributes to the outer layer of the new bulge, and the middle ORS contributes to the hair germ. Some of the lower ORS cells become the differentiated inner keratin 6+ (K6+) bulge cells, which provide inhibitory signals to Bu-SCs, raising their activation threshold for the next hair cycle. (b) During telogen, K6+ bulge cells produce BMP6 and FGF-18, dermal fibroblasts (DFs) produce BMP4 and subcutaneous adipocytes express BMP2. Together, these factors maintain Bu-SCs and hair germ in quiescence. At the transition to anagen, BMP2 and BMP4 are downregulated, whereas the expression of activation factors including noggin (NOG), FGF-7, FGF-10 and TGF-2 from dermal papillae and PDGF- from adipocyte precursor cells (APCs) is elevated. This, in turn, stimulates hair germ proliferation, and a new hair cycle is launched. Bu-SCs maintain their quiescent state until TAC matrix is generated and starts producing SHH.

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Emerging interactions between skin stem cells and their ...

Recently, Ive written about transition from iPS cell research to iPS cell large-scale manufacturing and automation. Ive described iPS cell process development in Cellular Dynamics International and New York Stem Cell Foundation Research Institute. Today, Id like to share presentations of 2 more players in the field Lonza and Roslin Cells. Both presentations were recorded at Stem Cell Meeting on the Mesa, held on October 14-16, 2013.

What was especially interesting to see a cost comparison between research and clinical-grade GMP-produced iPS cell lines:

(Screenshot from Lonza presentation at Stem Cell Meeting on the Mesa, 2013)

Interestingly, the major cost contributor in GMP-grade iPS cell production is a facility cost. I think, this is a first estimation of cost difference, presented for public.

The framework for establishing clinical-grade iPS cell manufacturing, nicely outlined in the recent article. Id also recommend you to read the following open access articles:

Tagged as: cost, iPS, manufacturing

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Clinical GMP-grade iPS cell production - Stem Cell Assays

The stem cell controversy is the consideration of the ethics of research involving the development, usage, and destruction of human embryos. Most commonly, this controversy focuses on embryonic stem cells. Not all stem cell research involves the creation, usage and destruction of human embryos. For example, adult stem cells, amniotic stem cells and induced pluripotent stem cells do not involve creating, using or destroying human embryos and thus are minimally, if at all, controversial.

The use of stem cells has been happening for decades. In 1998, scientists discovered how to extract stem cells from human embryos. This discovery led to moral ethics questions concerning research involving embryo cells, such as what restrictions should be made on studies using these types of cells? At what point does one consider life to begin? Is it just to destroy an embryo cell if it has the potential to cure countless numbers of patients? Political leaders are debating how to regulate and fund research studies that involve the techniques used to remove the embryo cells. No clear consensus has emerged. Other recent discoveries may extinguish the need for embryonic stem cells.[1]

Since stem cells have the ability to differentiate into any type of cell, they offer something in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed thanks to their ability to repair extensive tissue damage.[2]

Great levels of success and potential have been shown from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Embryonic stem cells can become all cell types of the body which is called totipotent. Adult stem cells are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity may exist, increasing the number of cell types a given adult stem cell can become. In addition, embryonic stem cells are considered more useful for nervous system therapies, because researchers have struggled to identify and isolate neural progenitors from adult tissues[citation needed]. Embryonic stem cells, however, might be rejected by the immune system - a problem which wouldn't occur if the patient received his or her own stem cells.

Some stem cell researchers are working to develop techniques of isolating stem cells that are as potent as embryonic stem cells, but do not require a human embryo.

Some believe that human skin cells can be coaxed to "de-differentiate" and revert to an embryonic state. Researchers at Harvard University, led by Kevin Eggan, have attempted to transfer the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[3] Another study published in August 2006 also indicates that differentiated cells can be reprogrammed to an embryonic-like state by introducing four specific factors, resulting in induced pluripotent stem cells.[4]

Researchers at Advanced Cell Technology, led by Robert Lanza, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[5] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[6] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos. "These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health (NIH) to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[7]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when utilized correctly, "can be differentiated towards cell types such as fat, bone, muscle, blood vessel, nerve and liver cells". The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs as well".[8]

The status of the human embryo and human embryonic stem cell research is a controversial issue as, with the present state of technology, the creation of a human embryonic stem cell line requires the destruction of a human embryo. Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They believe that embryonic stem cell research instrumentalizes and violates the sanctity of life and is tantamount to murder.[9] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, there have been estimates of at least 400,000 such embryos.[10] This has led some opponents of abortion, such as Senator Orrin Hatch, to support human embryonic stem cell research.[11] See Also Embryo donation.

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Stem cell controversy - Wikipedia, the free encyclopedia

Understanding Cancer -- Diagnosis and Treatment How Is Cancer Diagnosed?

The earlier cancer is diagnosed and treated, the better the chance of its being cured. Some types of cancer -- such as those of the skin, breast, mouth, testicles, prostate, and rectum -- may be detected by routine self-exam or other screening measures before the symptoms become serious. Most cases of cancer are detected and diagnosed after a tumor can be felt or when other symptoms develop. In a few cases, cancer is diagnosed incidentally as a result of evaluating or treating other medical conditions.

Cancer diagnosis begins with a thorough physical exam and a complete medical history. Laboratory studies of blood, urine, and stool can detect abnormalities that may indicate cancer. When a tumor is suspected, imaging tests such as X-rays, computed tomography (CT), magnetic resonance imaging (MRI), ultrasound, and fiber-optic endoscopy examinations help doctors determine the cancer's location and size. To confirm the diagnosis of most cancers , a biopsy needs to be performed in which a tissue sample is removed from the suspected tumor and studied under a microscope to check for cancer cells.

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Cancer Center: Types, Symptoms, Causes, Tests, and ...

Characterization of isolated human SHEDs and DPSCs for use in transplantation studies. Flow cytometry analysis showed that the SHEDs and DPSCs expressed a set of mesenchymal stem cell (MSC) markers (i.e., CD90, CD73, and CD105), but not endothelial/hematopoietic markers (i.e., CD34, CD45, CD11b/c, and HLA-DR) (Table 1). Like human BMSCs, both the SHEDs and DPSCs exhibited adipogenic, chondrogenic, and osteogenic differentiation as described previously (refs. 16, 17, and data not shown). The majority of SHEDs and DPSCs coexpressed several neural lineage markers: nestin (neural stem cells), doublecortin (DCX; neuronal progenitor cells), III-tubulin (early neuronal cells), NeuN (mature neurons), GFAP (neural stem cells and astrocytes), S-100 (Schwann cells), and A2B5 and CNPase (oligodendrocyte progenitor cells), but not adenomatous polyposis coli (APC) or myelin basic protein (MBP) (mature oligodendrocytes) (Figure 1A and Table 1). This expression profile was confirmed by immunohistochemical analyses (Figure 1B).

Characterization of the SHEDs and DPSCs used for transplantation. (A) Flow cytometry analysis of the neural cell lineage markers expressed in SHEDs. Note that most of the SHEDs and DPSCs coexpressed neural stem and multiple progenitor markers, but not mature oligodendrocytes (APC and MBP). (B) Confocal images showing SHEDs coexpressed nestin, GFAP, and DCX. SHEDs also expressed markers for oligodendrocyte progenitor cells (A2B5 and CNPase), but not for mature oligodendrocytes (APC and MBP). Scale bar: 10 m. (C) Real-time RT-PCR analysis of the expression of neurotrophic factors. Results are expressed as fold increase compared with the level expressed in skin fibroblasts. Data represent the average measurements for each cell type from 3 independent donors. This set of experiments was repeated twice and yielded similar results. Data represent the mean SEM. *P < 0.01 compared with BMSCs and fibroblasts (Fbs).

Flow cytometry of stem cells from humans

Next, we examined the expression of representative neurotrophic factors by real-time PCR. Both the SHEDs and DPSCs expressed glial cellderived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) at more than 3 to 5 times the levels expressed by skin-derived fibroblasts or BMSCs (Figure 1C).

We further characterized the transcriptomes of SHEDs and BMSCs by cDNA microarray analysis. This gene expression analysis revealed a 2.0-fold difference in the expression of 3,318 of 41,078 genes between SHEDs and BMSCs. Of these, 1,718 genes were expressed at higher levels in the SHEDs and 1,593 genes were expressed at lower levels (data not shown). The top 30 genes showing higher expression in the SHEDs were in the following ontology categories: extracellular and cell surface region, cell proliferation, and tissue/embryonic development (Table 2).

Functional gene classification in SHEDs versus BMSCs

SHEDs and DPSCs promoted locomotor recovery after SCI. To compare the neuroregenerative activities of human SHEDs and DPSCs with those of human BMSCs and human skin fibroblasts, we transplanted the cells into the completely transected SCs, as described in Methods, and evaluated locomotion recovery using the Basso, Beattie, Bresnahan locomotor rating scale (BBB scale) (24). Remarkably, the animals that received SHEDs or DPSCs exhibited a significantly higher BBB score during the entire observation period, compared with BMSC-transplanted, fibroblast-transplanted, or PBS-injected control rats (Figure 2A). Importantly, their superior recoveries were evident soon after the operation, during the acute phase of SCI. After the recovery period (5 weeks after the operation), the rats that had received SHEDs were able to move 3 joints of hind limb coordinately and walk without weight support (P < 0.01; Supplemental Videos 1 and 2), while the BMSC- or fibroblast-transplanted rats exhibited only subtle movements of 12 joints. These results demonstrate that the transplantation of SHEDs or DPSCs during the acute phase of SCI significantly improved the recovery of hind limb locomotor function. Since the level of recovery was similar in the SHED- and DPSC-transplanted rats, we focused on the phenotypical examination of SHED-transplanted rats to elucidate how tooth-derived stem cells promoted the regeneration of the completely transected rat SC.

Engrafted SHEDs promote functional recovery of the completely transected SC. (A) Time course of functional recovery of hind limbs after complete transection of the SC. A total of 1 106 SHEDs, DPSCs, BMSCs, or fibroblasts were transplanted into the SCI immediately after transection. Data represent the mean SEM. **P < 0.001, *P < 0.01 compared with SCI models injected with PBS. (BD) Representative images (B and C) and quantification (D) of NF-Mpositive nerve fibers in sagittal sections of a completely transected SC, at 8 weeks after SCI. Dashed lines outline the SC. Insets are magnified images of boxed areas in B and C. (D) Nerve fiber quantification, representing the average of 3 experiments performed under the same conditions. The x axis indicates specific locations along the rostrocaudal axis of the SC (3 mm rostral and caudal to the epicenter), and y axis indicates the percentage of NF-Mpositive fibers compared with that of the sham-operated SCs at the ninth thoracic spinal vertebrate (Th9) level. Data represent the mean SEM. *P < 0.05 compared with SCI models injected with PBS. Scale bars: 100 m and inset 20 m (B) and 50 m (C). Asterisks in B and C indicate the epicenter of the lesion.

SHEDs regenerated the transected corticospinal tract and raphespinal serotonergic axons. To examine whether engrafted SHEDs affect the preservation of neurofilaments, we performed immunohistochemical analyses with an antineurofilament M (NF-M) mAb, 8 weeks after transection. Compared with the PBS-treated control SCs, the SHED-transplanted SCs exhibited greater preservation of NF-positive axons from 3 mm rostral to 3 mm caudal to the transected lesion site (Figure 2, B and C; asterisk indicates epicenter). The percentages of NF-positive axons in the epicenter of the SHED-transplanted and control SCs were 35.8% 13.0% and 8.7% 3.4%, respectively, relative to sham-treated SCs (Figure 2D).

Regeneration of both the corticospinal tract (CST) and the descending serotonergic raphespinal axons is important for the recovery of hind limb locomotor function in rat SCI. We therefore examined whether these axons had extended beyond the epicenter in the SHED-transplanted SCs. The CST axons were traced with the anterograde tracer biotinylated dextran amine (BDA), which was injected into the sensorimotor cortex. The serotonergic raphespinal axons were immunohistochemically detected by a mAb that specifically reacts with serotonin (5-hydroxytryptamine [5-HT]), which is synthesized within the brain stem. We found that both BDA- and 5-HTpositive fibers extended as far as 3 mm caudal to the epicenter in the SHED-transplanted but not the control group (Figures 3 and 4). Furthermore, some BDA- and 5-HTpositive boutons could be seen apposed to neurons in the caudal stump (Figure 3D and Figure 4C), suggesting that the regenerated axons had established new neural connections. Notably, although the number of descending axons extending beyond the epicenter was small, we observed many of them penetrating the scar tissue of the rostral stump (Figure 3A and Figure 4A). The percentages of 5-HTpositive axons of the SHED-transplanted SCs at 1 and 3 mm rostral to the epicenter were 58.9% 3.9% and 78.3% 7.4% relative to sham-treated SC, respectively (Figure 4D). These results demonstrate that the engrafted SHEDs promoted the recovery of hind limb locomotion via the preservation and regeneration of transected axons, even in the microenvironment of the damaged CNS.

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Human Dental Pulp-Derived Stem Cells Promote Locomotor ...

High levels of active TGF- in the bone marrow and abnormalities in bone remodeling are associated with multiple skeletal disorders. Genetic mutations in the TGF- signaling pathway cause premature activation of matrix latent TGF- and may manifest with various skeletal defects. There are additional diseases that result in high levels of active TGF-, which may contribute to the pathology. Here, we discuss how abnormal TGF- signaling results in uncoupled bone remodeling, mainly by loss of site-directed recruitment of MSCs that causes aberrant bone formation. Direct or indirect inhibition of TGF- signaling may provide potential therapeutic options for these disorders.

Genetic disorders. The critical role of TGF-1 in the reversal phase of bone remodeling is demonstrated by the range of skeletal disorders resulting from mutations in genes involved in TGF-1 signaling. Camurati-Engelmann disease (CED), characterized by a fusiform thickening of the diaphysis of the long bones and skull, is caused by mutations in TGFB1 that result in premature activation of TGF-1 (7174). Approximately 11 different TGFB1 mutations have been identified from families affected by CED (75, 76). All of the mutations are located in the region encoding LAP, either destabilizing LAP disulfide bridging or affecting secretion of the protein, both of which increase TGF-1 signaling, as confirmed by in vitro cell cultures and mouse models. Bone histology sections from patients with CED show decreased trabecular connectivity despite normal bone histomorphometric parameters with respect to osteoblast and osteoclast numbers (76, 77), suggestive of uncoupled bone remodeling. In vitro, the ratio of active to total TGF-1 in conditioned medium from cells expressing the CED mutant TGF-1 is significantly higher and enhances MSC migration (18). Targeted recruitment of MSCs to the bone-remodeling site is likely disrupted, secondary to loss of a TGF- gradient.

Elevations in TGF- signaling have also been observed in many genetic connective tissue disorders with craniofacial, skeletal, skin, and cardiovascular manifestations, including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), and Shprintzen-Goldberg syndrome (SGS). MFS is caused by mutations in fibrillin and often results in aortic dilation, myopia, bone overgrowth, and joint laxity. Fibrillin is deposited in the ECM and normally binds TGF-, rendering it inactive. In MFS, the decreased level of fibrillin enhances TGF- activity (78). LDS is caused by inactivating mutations in genes encoding TRI and TRII (79). Physical manifestations include arterial aneurysms, hypertelorism, bifid uvula/cleft palate, and bone overgrowth resulting in arachnodactyly, joint laxity, and scoliosis. Pathologic analyses of affected tissue suggest chronically elevated TGF- signaling, despite the inactivating mutation (79). The mechanism of enhanced TGF- signaling remains under investigation. SGS is caused by mutations in the v-ski avian sarcoma viral oncogene homolog (SKI; refs. 80, 81) and causes physical features similar to those of MFS plus craniosynostosis. SKI negatively regulates SMAD-dependent TGF- signaling by impeding SMAD2 and SMAD3 activation, preventing nuclear translocation of the SMAD4 complex, and inhibiting TGF- target gene output by competing with p300/CBP for SMAD binding and recruiting transcriptional repressor proteins, such as mSin3A and HDACs (8284).

The neurocutaneous syndrome neurofibromatosis type 1 (NF1) has been noted to have skeletal features similar to those of CED, MFS, and LDS, including kyphoscoliosis, osteoporosis, and tibial pseudoarthrosis. Hyperactive TGF-1 signaling has been implicated as the primary factor underlying the pathophysiology of the osseous defects in Nf1fl/Col2.3Cre mice, a model of NF1 that closely recapitulates the skeletal abnormalities found in human disease (85). The exact mechanisms mediating mutant neurofibrominassociated enhancement of TGF- production and signaling remain unknown.

Osteoarthritis. While genetic disorders are rare, they have provided critical insight into the pathophysiology of more common disorders. Uncoupled bone remodeling accompanies the onset of osteoarthritis. TGF-1 is activated in subchondral bone in response to altered mechanical loading in an anterior cruciate ligament transection (ACLT) mouse model of osteoarthritis (86). High levels of active TGF-1 induced formation of nestin+ MSC clusters via activation of ALK5-SMAD2/3. MSCs underwent osteoblast differentiation in these clusters, leading to formation of marrow osteoid islets. Transgenic expression of active TGF-1 in osteoblastic cells alone was sufficient to induce osteoarthritis, whereas direct inhibition of TGF- activity in subchondral bone attenuated the degeneration of articular cartilage. Knockout of Tgfbr2 in nestin+ MSCs reduced osteoarthritis development after ACLT compared with wild-type mice, which confirmed that MSCs are the target cell population of TGF- signaling. High levels of active TGF-1 in subchondral bone likely disrupt the TGF- gradient and interfere with targeted migration of MSCs. Furthermore, mutations of ECM proteins that bind to latent TGF-s, such as small leucine-rich proteoglycans (87) and fibrillin (88), or mutations in genes involved in activation of TGF-, such as in CED (76) and LDS (89), are associated with high osteoarthritis incidence. Osteoblast differentiation of MSCs in aberrant locations appears histologically as subchondral bone osteoid islets and alters the thickness of the subchondral plate and calcified cartilage zone, changes known to be associated with osteoarthritis (90, 91). A computer-simulated model found that a minor increase in the size of the subchondral bone (1%2%) causes significant changes in the mechanical load properties on articular cartilage, which likely leads to degeneration (86). Importantly, inhibition of the TGF- signaling pathway delayed the development of osteoarthritis in both mouse and rat models (86).

MSCs in bone loss. Aging leads to deterioration of tissue and organ function. Skeletal aging is especially dramatic: bone loss in both women and men begins as early as the third decade, immediately after peak bone mass. Aging bone loss occurs when bone formation does not adequately compensate for osteoclast bone resorption during remodeling. Age-associated osteoporosis was previously believed to be due to a decline in survival and function of osteoblasts and osteoprogenitors; however, recent work by Park and colleagues found that mature osteoblasts and osteoprogenitors are actually nonreplicative cells and require constant replenishment from bone marrow MSCs (92). When MSCs fail to migrate to bone-resorptive sites or are unable to commit and differentiate into osteoblasts, new bone formation is impaired. Therefore, insufficient recruitment of MSCs, or their differentiation to osteoblasts, at the bone remodeling surface may contribute to the decline in bone formation in the elderly.

There are multiple hypotheses regarding the decreased osteogenic potential of MSCs during aging. For example, during aging, the bone marrow environment has an increased concentration of ROS and lipid oxidation that may decrease osteoblast differentiation, yet increase osteoclast activity (93, 94). MSCs also undergo senescence, which decreases proliferative capacity and contributes to decreased bone formation (95, 96). Cellular senescence involves the secretion of a plethora of factors, including TGF-, which induces expression of cyclin-dependent kinase inhibitors 2A and 2B (p16INK4A and p15INK4B, respectively; refs. 97).

Microgravity experienced by astronauts during spaceflight causes severe physiological alterations in the human body, including a 1%2% loss of bone mass every month during spaceflight (98). Several studies have shown decreases in osteoblastic markers of bone formation and increases in bone resorption (99101). The underlying molecular mechanisms responsible for the apparent concurrent decrease in bone formation and increase in bone resorption remain under investigation. Work by the McDonald group suggests that bone remodeling may become uncoupled under zero-gravity conditions secondary to decreased RhoA activity and resultant changes in actin stress fiber formation (102). In modeled microgravity, cultured human MSCs exhibit disruption of F-actin stress fibers within three hours of initiation of microgravity; the fibers are completely absent after seven days. RhoA activity is significantly reduced, and introduction of an adenoviral construct expressing constitutively active RhoA can reverse the elimination of stress fibers, significantly increasing markers of osteoblast differentiation (102). Under zero-gravity conditions, RhoA is unable to bind to its receptor, and a sufficient number of MSCs may not be able to migrate correctly to the bone-resorptive site for osteoblast differentiation, ultimately leading to bone loss with every cycle of remodeling.

Bone metastases are a frequent complication of cancer and often have both osteolytic and osteoblastic features, indicative of dysregulated bone remodeling. The importance of the bone marrow microenvironment contributing to the spread of cancer was first described in 1889 (103), postulating that tumor cells can grow only if they are in a conducive environment. Activation of matrix TGF- during bone remodeling plays a central role in the initiation of bone metastases and tumor expansion by regulating osteolytic and prometastatic factors (reviewed in refs. 104110). For example, TGF- can induce osteoclastic bone destruction by upregulating tumor cell expression of PTHrP and IL-11. Additionally, upregulation of CXCR4 by TGF- may home cancer cells to bones.

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JCI - Bone marrow mesenchymal stem cells and TGF- ...

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 ...

World J Stem Cells. 2014 Apr 26; 6(2): 120133.

Venkata Ramesh Dasari, Krishna Kumar Veeravalli, Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, United States

Dzung H Dinh, Department of Neurosurgery and Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, Peoria, IL 61656, United States

Correspondence to: Dzung H Dinh, MD, Department of Neurosurgery and Illinois Neurological Institute, University of Illinois College of Medicine at Peoria, One Illini Drive, Peoria, IL 61605, United States. ude.ciu@hnidd

Telephone: +1- 309-6552642 Fax: +1-309-6713442

Received 2013 Oct 30; Revised 2014 Feb 19; Accepted 2014 Mar 11.

With technological advances in basic research, the intricate mechanism of secondary delayed spinal cord injury (SCI) continues to unravel at a rapid pace. However, despite our deeper understanding of the molecular changes occurring after initial insult to the spinal cord, the cure for paralysis remains elusive. Current treatment of SCI is limited to early administration of high dose steroids to mitigate the harmful effect of cord edema that occurs after SCI and to reduce the cascade of secondary delayed SCI. Recent evident-based clinical studies have cast doubt on the clinical benefit of steroids in SCI and intense focus on stem cell-based therapy has yielded some encouraging results. An array of mesenchymal stem cells (MSCs) from various sources with novel and promising strategies are being developed to improve function after SCI. In this review, we briefly discuss the pathophysiology of spinal cord injuries and characteristics and the potential sources of MSCs that can be used in the treatment of SCI. We will discuss the progress of MSCs application in research, focusing on the neuroprotective properties of MSCs. Finally, we will discuss the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

Keywords: Spinal cord injury, Mesenchymal stem cells, Bone marrow stromal cells, Umbilical cord derived mesenchymal stem cells, Adipose tissue derived mesenchymal stem cells

Core tip: Despite our deeper understanding of the molecular changes that occurs after the spinal cord injury (SCI), the cure for paralysis remains elusive. In this review, the pathophysiology of SCI and characteristics and potential sources of mesenchymal stem cells (MSCs) that can be used in the treatment of SCI were discussed. We also discussed the progress of application of MSCs in research focusing on the neuroprotective properties of MSCs. Finally, we discussed the results from preclinical and clinical trials involving stem cell-based therapy in SCI.

Traumatic spinal cord injury (SCI) continues to be a devastating injury to affected individuals and their families and exacts an enormous financial, psychological and emotional cost to them and to society. Despite years of research, the cure for paralysis remains elusive and current treatment is limited to early administration of high dose steroids and acute surgical intervention to minimize cord edema and the subsequent cascade of secondary delayed injury[1-3]. Recent advances in neurosciences and regenerative medicine have drawn attention to novel research methodologies for the treatment of SCI. In this review, we present our current understanding of spinal cord injury pathophysiology and the application of mesenchymal stem cells (MSCs) in the treatment of SCI. This review will be more useful for basic and clinical investigators in academia, industry and regulatory agencies as well as allied health professionals who are involved in stem cell research.

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Mesenchymal stem cells in the treatment of spinal cord ...

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Haematopoietic stem cells and early lymphoid progenitors ...

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 ...

Sickle-cell disease (SCD), also known as sickle-cell anaemia (SCA) and drepanocytosis, is a hereditary blood disorder, characterized by an abnormality in the oxygen-carrying haemoglobin molecule in red blood cells. This leads to a propensity for the cells to assume an abnormal, rigid, sickle-like shape under certain circumstances. Sickle-cell disease is associated with a number of acute and chronic health problems, such as severe infections, attacks of severe pain ("sickle-cell crisis"), and stroke, and there is an increased risk of death.

Sickle-cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene, one from each parent. Several subtypes exist, depending on the exact mutation in each haemoglobin gene. A person with a single abnormal copy does not experience symptoms and is said to have sickle-cell trait. Such people are also referred to as carriers.

The complications of sickle-cell disease can be prevented to a large extent with vaccination, preventive antibiotics, blood transfusion, and the drug hydroxyurea/hydroxycarbamide. A small proportion requires a transplant of bone marrow cells.

Almost 300,000 children are born with a form of sickle-cell disease every year, mostly in sub-Saharan Africa, but also in other parts of the world such as the West Indies and in people of African origin elsewhere in the world. In 2013 it resulted in 176,000 deaths up from 113,000 deaths in 1990.[1] The condition was first described in the medical literature by the American physician James B. Herrick in 1910, and in the 1940s and 1950s contributions by Nobel prize-winner Linus Pauling made it the first disease where the exact genetic and molecular defect was elucidated.

Sickle-cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.[2]

The terms "sickle-cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD. SCD results in anemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, sequestration crisis, haemolytic crisis, and others. Most episodes of sickle-cell crises last between five and seven days.[3] "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."[4]

The vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Painful crises are treated with hydration, analgesics, and blood transfusion; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia devices are commonly used in this setting. Vaso-occlusive crisis involving organs such as the penis[5] or lungs are considered an emergency and treated with red-blood cell transfusions. Incentive spirometry, a technique to encourage deep breathing to minimise the development of atelectasis, is recommended.[6]

Because of its narrow vessels and function in clearing defective red blood cells, the spleen is frequently affected.[7] It is usually infarcted before the end of childhood in individuals suffering from sickle-cell anemia. This spleen damage increases the risk of infection from encapsulated organisms;[8][9] preventive antibiotics and vaccinations are recommended for those lacking proper spleen function.

Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in hemoglobin levels with the potential for hypovolemic shock. Sequestration crises are considered an emergency. If not treated, patients may die within 12 hours due to circulatory failure. Management is supportive, sometimes with blood transfusion. These crises are transient, they continue for 34 hours and may last for one day.[10]

Acute chest syndrome (ACS) is defined by at least two of the following signs or symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality, respiratory symptoms, or hypoxemia.[11] It is the second-most common complication and it accounts for about 25% of deaths in patients with SCD, majority of cases present with vaso-occlusive crises then they develop ACS.[12][13] Nevertheless, about 80% of patients have vaso-occlusive crises during ACS.

More here:
Sickle-cell disease - Wikipedia, the free encyclopedia

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 ...

See comment in PubMed Commons below N Engl J Med. 2012 Oct 18;367(16):1487-96. doi: 10.1056/NEJMoa1203517. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Couban S, Ehninger G, Johnston L, Maziarz RT, Pulsipher MA, Porter DL, Mineishi S, McCarty JM, Khan SP, Anderlini P, Bensinger WI, Leitman SF, Rowley SD, Bredeson C, Carter SL, Horowitz MM, Confer DL; Blood and Marrow Transplant Clinical Trials Network. Collaborators (182)

Horowitz MM, Carter SL, Confer DL, DiFronzo N, Wagner E, Merritt W, Wu R, Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, Couban S, Anderlini P, Bensinger WI, Leitman SF, Rowley SD, Carter SL, Karanes C, Horowitz MM, Confer DL, Allen C, Colby C, Gurgol C, Knust K, Foley A, King R, Mitchell P, Couban S, Pulsipher MA, Ehninger G, Johnston L, Khan SP, Maziarz RT, McCarty JM, Mineishi S, Porter DL, Bredeson C, Anasetti C, Lee S, Waller EK, Wingard JR, Cutler CS, Westervelt P, Woolfrey A, Logan BR, Carter SL, Lee SJ, Waller EK, Anasetti C, Logan BR, Lee SJ, Stadtmauer E, Wingard J, Vose J, Lazarus H, Cowan M, Wingard J, Westervelt P, Litzow M, Wu R, Geller N, Carter S, Confer D, Horowitz M, Poland N, Krance R, Carrum G, Agura E, Nademanee A, Sahdev I, Cutler C, Horwitz ME, Kurtzberg J, Waller EK, Woolfrey A, Rowley S, Brochstein J, Leber B, Wasi P, Roy J, Jansen J, Stiff PJ, Khan S, Devine S, Maziarz R, Nemecek E, Huebsch L, Couban S, McCarthy P, Johnston L, Shaughnessy P, Savoie L, Ball E, Vaughan W, Cowan M, Horn B, Wingard J, Silverman M, Abhyankar S, McGuirk J, Yanovich S, Ferrara J, Weisdorf D, Faber E Jr, Selby G, Rooms LM, Porter D, Agha M, Anderlini P, Lipton J, Pulsipher MA, Pulsipher MA, Shepherd J, Toze C, Kassim A, Frangoul H, McCarty J, Hurd D, DiPersio J, Westervelt P, Shenoy S, Agura E, Culler E, Axelrod F, Chambers L, Senaldi E, Nguyen KA, Engelman E, Hartzman R, Sutor L, Dickson L, Nademanee A, Khalife G, Lenes BA, Eames G, Sibley D, Gale P, Antin J, Ehninger G, Newberg NR, Gammon R, Montgomery M, Mair B, Rossmann S, Wada R, Waxman D, Ranlett R, Silverman M, Herzig G, Fried M, Atkinson E, Weitekamp L, Bigelow C, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Miller JP, Price T, Young C, Hilbert R, Oh D, Cable C, Smith JW, Kalmin ND, Schultheiss K, Beck T, Lankiewicz MW, Sharp D.

Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia.

We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37).

The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, -3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse.

We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute-National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.).

Survival after Randomization in the Intention-to-Treat Analysis

The P value is from a stratified binomial comparison at the 2-year point. The P value from a stratified log-rank test was also not significant. A total of 75 patients in each group were still alive at 36 months.

N Engl J Med. 2012 October 18;367(16):10.1056/NEJMoa1203517.

Outcomes after Transplantation, According to Study Group

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Peripheral-blood stem cells versus bone marrow from ...

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ProgeniDerm Anti-Senescence Skin Stem Cell Serum ...

Tobi is a six-year-old cocker spaniel whose hind legs were paralyzed after he suffered a herniated disc in his spine. Although Tobi will never fully regain the use of his legs, he has benefitted from a clinical trial involving stem cell transplantation in dogs that is currently underway at North Carolina State University.

See video presentation: Stem cell treatments for paralyzed dogs.

Dr. Natasha Olby, professor of neurology at the NC State College of Veterinary Medicine, specializes in researching treatments for long-term paralysis in dogs. According to Dr. Olby, even in the case of severe spinal cord injury all may not be lost in terms of spinal cord function there may still be salvageable, living nerves and nerve fibers, or axons, bridging the site of the injury that could still transmit signals if they had a little help.

Obviously, researchers would love to be able to replace all the lost neurons and axons and restore normal connections in a damaged spinal cord. But that sort of treatment is not yet possible. On the other hand, targeting surviving nerves and axons that are still crossing the site of the injury and restoring their conductivity is more attainable.

Often, these damaged nerves have lost the myelin sheath, fatty material that coats axons and allows them to conduct signals. Dr. Olby wants to restore the myelin sheath to these surviving axons by taking fat cells from the patient and turning them into stem cells that can be combined with nerve cells and injected into the site of the damage, regrowing the sheath. Even though she is still in the early stages of a randomized clinical trial, the results thus far are encouraging.

Dogs like Tobi will not be the only beneficiaries of Dr. Olbys research. If the therapy produces positive results in dogs, then translating the treatment to humans is a natural next step. And in humans, even very small improvements have the capacity to radically transform quality of life.

Even if this procedure produced an effect in a person as small as giving him or her partial control of one finger, that could allow the patient to use a computer, which opens up a whole new world of possibilities in terms of communication and interaction with the outside world, Dr. Olby says.

-- Tracey Peake

Dr. Olbys research is funded by the Morris Animal Foundation and is one of the clinical trials underway in the Neurology Service within the Randall B. Terry, Jr. Companion Animal Veterinary Medical Center. For more information on the clinical trial, visit the "call for patients" web page.

Posted Feb. 14, 2012

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CVM Stem Cell Study Benefits Dogs with Spinal Cord Injuries