Helping Cultured Stem Cells Roll

[Anonymous]

Helping Cultured Stem Cells Roll

Researchers who study mesenchymal stem cells know that these cells hold enormous therapeutic potential to differentiate on cue into new bone or cartilage-forming cells that can regenerate damaged tissue. It is tricky to deliver these cells reliably to a site of injury or inflammation, preferably via direct infusion into the bloodstream. The problem is that typically less than 1% of cultured mesen­chymal stem cells have the ability to home in on their target once infused into the blood system.

The reason: In culture, most either lose or do not possess the needed homing receptors that typically must be displayed on the cell surface of mesenchymal stem cells. This shortcoming has led to various strategies to coax more cultured mesenchymal stem cells not only to find their targets, but also to adhere to them.

How­ever, the mesenchymal stem cells in the blood stream arrive via a rolling landing onto their target tissue. This landing helps the stem cells to decelerate and initiate the subsequent steps in the ad­hesion cascade, in­cluding firm adhesion and passage into the tissue. Cur­rent strategies have yet to mimic this natural rolling landing and trigger the natural adhesion cascade. A team of Na­tional Institute of Den­tal and Craniofacial Research (NIDCR) grantees and colleagues previously developed a versatile cell-engineering approach that allowed them to attach adhesion molecules to the surface of stem cells, improving their rolling response and thus homing ability.

Now they are taking the next step in engineering mesenchymal stem cells with self-assembled lipid vesicles on their surface that transiently present molecules that promote cell rolling. “This method presents an alternative cell membrane engineering ap­proach to introduce a ligand of interest on the cell membrane for short duration, in contrast to enzymatic and covalent modification methods….of­fers a platform that can be used to investigate engineered stem cell homing and interrogate the biology of cell homing.”

        

[drmithila]

Sources of stem cells
Veterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons.[62][63][64] There are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different donor within the same species[65][60] and autologous mesenchymal stem cells, derived from the patient prior to use in various treatments.[58] A third category, xenogenic stem cells, or stem cells derived from different species, are used primarily for research purposes, especially for human treatments.[66]
Most stem cells intended for regenerative therapy are generally isolated either from the patient’s bone marrow or from adipose tissue.[60][59] Mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments, as well as muscle, neural and other progenitor tissues, they have been the main type of stem cells studied in the treatment of diseases affecting these tissues.[63][67] The number of stem cells transplanted into damaged tissue may alter efficacy of treatment. Accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells.[60][59] Although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells.[68][69] While it is thought that bone-marrow derived stem cells are preferred for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation.[58]
New sources of mesenchymal stem cells are currently being researched, including stem cells present in the skin and dermis which are of interest because of the ease at which they can be harvested with minimal risk to the animal.[70] Hematopoetic stem cells have also been discovered to be travelling in the blood stream and possess equal differentiating ability as other mesenchymal stem cells, again with a very non-invasive harvesting technique.[71]
There has been more recent interest in the use of extra embryonic mesenchymal stem cells. Research is currently underway to examine the differentiating capabilities of stem cells found in the umbilical cord, yolk sac and placenta of different animals. These stem cells are thought to have more differentiating ability than their adult counterparts, including the ability to more readily form tissues of endodermal and ectodermal origin. [61]
[edit]Stem cells and Soft Tissue Repair
Because of the general positive healing capabilities of stem cells, they have gained interest for the treatment of cutaneous wounds. This is important interest for those with reduced healing capabilities, like diabetics and those undergoing chemotherapy. In one trial, stem cells were isolated from the Wharton’s jelly of the umbilical cord. These cells were injected directly into the wounds. Within a week, full re-epithelialization of the wounds had occurred, compared to minor re-epithelialization in the control wounds. This also showed the capabilities of mesenchymal stem cells in the repair of epidermal tissues.[72]
Soft palate defects in horses are caused by a failure of the embryo to fully close at the midline during embryogenesis. These are often not found until after they have become worse because of the difficulty in visualizing the entire soft palate. This lack of visualization is thought to also contribute to the low success rate in surgical intervention to repair the defect. As a result, the horse often has to be euthanized. Recently, the use of mesenchymal stem cells has been added to the conventional treatments. After the surgeon has sutured the palate closed, autologous mesenchymal cells are injected into the soft palate. The stem cells were found to be integrated into the healing tissue especially along the border with the old tissue. There was also a large reduction in the number of inflammatory cells present, which is thought to aid in the healing process.

 

        

[drsushant]

Medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering.
A number of current stem cell treatments already exists, although they are not commonly used because they tend to be experimental and not very cost-effective.
In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat cancer, spinal cord injuries, and muscle damage, amongst a number of other diseases and impairments.
For more information about the topic Stem cell treatments, read the full article at Wikipedia.org, or see the following related articles:
Embryonic stem cell — Embryonic stem cells (ESCs) are stem cells derived from the undifferentiated inner mass cells of a human embryo. Embryonic stem cells are … > read more
Bone marrow transplant — Bone marrow transplantation (BMT) or hematopoietic stem cell transplantation (HSCT) is a medical procedure in the field of hematology and oncology … > read more
Natural killer cell — Natural killer cells (also known as NK cells, K cells, and killer cells) are a type of lymphocyte (a white blood cell) and a component of innate … > read more
Metastasis — Metastasis is the spread of cancer from its primary site to other places in the body (e.g., brain, liver). Cancer cells can break away from a primary .

 

        

[drmithila]

Embryonic stem cells (ES cells) are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo.[1] Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the embryoblast or inner cell mass (ICM) results in destruction of the fertilized human embryo, which raises ethical issues. Those issues include whether or not a human life at the embryonic stage should be granted the moral status of a human being as it is with a child or an adult.Safety: reducing the risk of teratoma and other cancers as a side effect

The major concern with the possible transplantation of ESC into patients as therapies is their ability to form tumors including teratoma.[20] Safety issues prompted the FDA to place a hold on the first ESC clinical trial however no tumors were observed.
The main strategy to enhance the safety of ESC for potential clinical use is to differentiate the ESC into specific cell types (e.g. neurons, muscle, liver cells) that have reduced or eliminated ability to cause tumors. Following differentiation, the cells are subjected to sorting by flow cytometry for further purification. ESC are predicted to be inherently safer than IPS cells because they are not genetically modified with genes such as c-Myc that are linked to cancer. Nonetheless, ESC express very high levels of the iPS inducing genes and these genes including Myc are essential for ESC self-renewal and pluripotency,[21] and potential strategies to improve safety by eliminating Myc expression are unlikely to preserve the cells’ "stemness"Embryonic stem cells have the potential to grow indefinitely in a laboratory environment and can differentiate into almost all types of bodily tissue. This makes embryonic stem cells a prospect for cellular therapies to treat a wide range of diseases.[18]
]Human potential and humanity
This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:
Embryos are not equivalent to human life while they are still incapable of surviving outside the womb (i.e. they only have the potential for life).
More than a third of zygotes do not implant after conception.[19][20] Thus, far more embryos are lost due to chance than are proposed to be used for embryonic stem cell research or treatments.
Blastocysts are a cluster of human cells that have not differentiated into distinct organ tissue; making cells of the inner cell mass no more "human" than a skin cell.[18]
Some parties contend that embryos are not humans, believing that the life of Homo sapiens only begins when the heartbeat develops, which is during the 5th week of pregnancy,[21] or when the brain begins developing activity, which has been detected at 54 days after conception.[22]
Efficiency
In vitro fertilization (IVF) generates large numbers of unused embryos (e.g. 70,000 in Australia alone).[18] Many of these thousands of IVF embryos are slated for destruction. Using them for scientific research uses a resource that would otherwise be wasted.[18]
While the destruction of human embryos is required to establish a stem cell line, no new embryos have to be destroyed to work with existing stem cell lines. It would be wasteful not to continue to make use of these cell lines as a resource.[18]
Abortions are legal in many countries and jurisdictions. The argument then follows that if these embryos are being destroyed anyway, why not use them for stem cell research or treatments?
Superiority
This is usually presented as a counter-argument to using adult stem cells as an alternative that doesn’t involve embryonic destruction.
Embryonic stem cells make up a significant proportion of a developing embryo, while adult stem cells exist as minor populations within a mature individual (e.g. in every 1,000 cells of the bone marrow, only 1 will be a usable stem cell). Thus, embryonic stem cells are likely to be easier to isolate and grow ex vivo than adult stem cells.[18]
Embryonic stem cells divide more rapidly than adult stem cells, potentially making it easier to generate large numbers of cells for therapeutic means. In contrast, adult stem cell might not divide fast enough to offer immediate treatment.[18]
Embryonic stem cells have greater plasticity, potentially allowing them to treat a wider range of diseases.[18]
Adult stem cells from the patient’s own body might not be effective in treatment of genetic disorders. Allogeneic embryonic stem cell transplantation (i.e. from a healthy donor) may be more practical in these cases than gene therapy of a patient’s own cell.[18]
DNA abnormalities found in adult stem cells that are caused by toxins and sunlight may make them poorly suited for treatment.[18]
Embryonic stem cells have been shown to be effective in treating heart damage in mice.[18]
Embryonic stem cells have the potential to cure chronic and degenerative diseases which current medicine has been unable to effectively treat.
Individuality
Before the primitive streak is formed when the embryo attaches to the uterus at approximately 14 days after fertilization, a single fertilized egg can split in two to form identical twins, or a pair of embryos that would have resulted in fraternal twins can fuse together and develop into one person (a tetragametic chimera). Since a fertilized egg has the potential to be two individuals or half of one, some believe it can only be considered a potential person, not an actual one. Those who subscribe to this belief then hold that destroying a blastocyst for embryonic stem cells is ethical.
]Viability
Viability is another standard under which embryos and fetuses have been regarded as human lives. In the United States, the 1973 Supreme Court case of Roe v. Wade concluded that viability determined the permissibility of abortions performed for reasons other than the protection of the woman’s health, defining viability as the point at which a fetus is "potentially able to live outside the mother’s womb, albeit with artificial aid."[24] The point of viability was 24 to 28 weeks when the case was decided and has since moved to about 22 weeks due to advancement in medical technology. Embryos used in medical research for stem cells are well below development that would enable viability.
Moral and ethical concerns
Many questions arise of this concern, Julian Savulescu [25] lists several arguments.
It is liable to abuse. It violates a person’s right to individuality, autonomy, self-hood. It allows eugenic selection.
His journal goes into details of the advantages of using stem cell lines mainly for therapeutic reasons with great emphasis on control. The main reason is that if this regeneration practice goes un-checked, there will be someone out there that will be "playing God."
Better alternatives"
This argument is used by opponents of embryonic destruction as well as researchers specializing in adult stem cell research.
Pro-life supporters often claim that the use of adult stem cells from sources such as umbilical cord blood has consistently produced more promising results than the use of embryonic stem cells.[26] Furthermore, adult stem cell research may be able to make greater advances if less money and resources were channeled into embryonic stem cell research.Embryonic stem cells have never produced therapies (to date, adult stem cells have been used in treatment). Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.
This argument remains hotly debated on both sides. Those critical of embryonic stem cell research point to a current lack of practical treatments, while supporters argue that advances will come with more time and that breakthroughs cannot be predicted.

 

        

[Drsumitra]

To build a tooth, a detailed recipe to instruct cells to differentiate towards proper lineages and form dental cells is needed. Researchers in the group of Professor Irma Thesleff at the Institute of Biotechnology in Helsinki, Finland have now found a marker for dental stem cells. They showed that the transcription factor Sox2 is specifically expressed in stem cells of the mouse front tooth.
Despite the development of new bioengineering protocols, building a tooth from stem cells remains a distant goal. Demand for it exists as loss of teeth affects oral health, quality of life, as well as one’s appearance. To build a tooth, a detailed recipe to instruct cells to differentiate towards proper lineages and form dental cells is needed. However, the study of stem cells requires their isolation and a lack of a specific marker has hindered studies so far.
Researchers in the group of Professor Irma Thesleff at the Institute of Biotechnology in Helsinki, Finland have now found a marker for dental stem cells. They showed that the transcription factor Sox2 is specifically expressed in stem cells of the mouse incisor (front tooth). The mouse incisor grows continuously throughout life and this growth is fueled by stem cells located at the base of the tooth. These cells offer an excellent model to study dental stem cells.
The researchers developed a method to record the division, movement, and specification of these cells. By tracing the descendants of genetically labeled cells, they also showed that Sox2 positive stem cells give rise to enamel-forming ameloblasts as well as other cell lineages of the tooth.
– Although human teeth don’t grow continuously, the mechanisms that control and regulate their growth are similar as in mouse teeth. Therefore, the discovery of Sox2 as a marker for dental stem cells is an important step toward developing a complete bioengineered tooth. In the future, it may be possible to grow new teeth from stem cells to replace lost ones, says researcher Emma Juuri, a co-author of the study

 

        

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