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Category Archives: Stem Cells

Stem cell transplant – NHS

Posted: December 27, 2022 at 12:40 am

A stem cell or bone marrow transplant replaces damaged blood cells with healthy ones. It can be used to treat conditions affecting the blood cells, such as leukaemia and lymphoma.

Stem cells arespecial cells produced bybone marrow (aspongytissue found in the centre of some bones) that can turn into different types of blood cells.

The 3 maintypes of blood cellthey can become are:

A stem cell transplant involves destroying any unhealthy blood cells and replacing them with stem cells removed from the blood or bone marrow.

Stem cell transplants are used to treat conditions in which the bone marrow is damaged and is no longer able to produce healthy blood cells.

Transplants can also be carried out to replace blood cells that are damaged or destroyed as a result of intensive cancer treatment.

Conditions that stem cell transplants can be used to treat include:

A stem cell transplant will usually only be carried out if other treatments have not helped, the potential benefits of a transplant outweigh the risks and you're in relatively good health, despite your underlying condition.

A stem cell transplant can involve taking healthy stem cells from the blood or bone marrow of one person ideally a close family member with the same or similar tissue type and transferring them to another person. This is called an allogeneic transplant.

It's also possible to remove stem cells from your own body and transplant them later, after any damaged or diseased cells have been removed. This is called an autologous transplant.

Astem celltransplant has 5 main stages. These are:

Having a stem cell transplant can be an intensive and challenging experience. You'll usually need to stay in hospital forat least a few weeks until the transplant starts to take effect and itcan take up toa year or longer to fully recover.

Read more about what happens during a stem cell transplant.

Stem celltransplants arecomplicated procedures with significant risks. It's important that you're aware of both the risks and possible benefits before treatment begins.

Possible problems you can have during or after the transplant process include:

Read more about the risks of having a stem cell transplant.

Ifit is not possible to use your own stem cells for the transplant, stem cells will need to come from a donor.

To improve the chances ofthetransplant being successful, donated stem cells need tocarry a special genetic marker known as a human leukocyte antigen (HLA) that'sidentical or very similar to that of the person receiving the transplant.

The best chance of getting a match is from a brother or sister, or sometimes another close family member. If there are no matches in your close family,a search of theBritish Bone Marrow Registry will be carried out.

Most peoplewill eventually find a donor in the registry,although a small number of people may find it very hard or impossibleto find a suitable match.

The NHS Blood and Transplant website and the Anthony Nolan website have more information about stem cell and bone marrow donation.

Page last reviewed: 07 September 2022Next review due: 07 September 2025

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Stem cells: a brief history and outlook – Science in the News

Posted: December 27, 2022 at 12:40 am

Stem cells have been the object of much excitement and controversy amongst both scientists and the general population. Surprisingly, though, not everybody understands the basic properties of stem cells, let alone the fact that there is more than one type of cell that falls within the stem cell category. Here, Ill lay out the basic concepts of stem cell biology as a background for understanding the stem cell research field, where it is headed, and the enormous promise it offers for regenerative medicine.

Fertilization of an egg cell by a sperm cell results in the generation of a zygote, the single cell that, upon a myriad of divisions, gives rise to our whole body. Because of this amazing developmental potential, the zygote is said to be totipotent. Along the way, the zygote develops into the blastocyst, which implants into the mothers uterus. The blastocyst is a structure comprising about 300 cells that contains two main regions: the inner cell mass (ICM) and the trophoblast. The ICM is made of embryonic stem cells (ES cells), which are referred to as pluripotent. They are able to give rise to all the cells in an embryo proper, but not to extra-embryonic tissues, such as the placenta. The latter originate from the trophoblast [].

Even though it is hard to pinpoint exactly when or by whom what we now call stem cells were first discovered, the consensus is that the first scientists to rigorously define the key properties of a stem cell were Ernest McCulloch and James Till. In their pioneering work in mice in the 1960s, they discovered the blood-forming stem cell, the hematopoietic stem cell (HSC) [2, 3]. By definition, a stem cell must be capable of both self-renewal (undergoing cell division to make more stem cells) and differentiation into mature cell types. HSCs are said to be multipotent, as they can still give rise to multiple cell types, but only to other types of blood cells (see Figure 1, left column). They are one of many examples of adult stem cells, which are tissue-specific stem cells that are essential for organ maintenance and repair in the adult body. Muscle, for instance, also possesses a population of adult stem cells. Called satellite cells, these muscle cells are unipotent, as they can give rise to just one cell type, muscle cells.

Therefore, the foundations of stem cell research lie not with the famous (or infamous) human embryonic stem cells, but with HSCs, which have been used in human therapy (such as bone marrow transplants) for decades. Still, what ultimately fueled the enormous impact that the stem cell research field has today is undoubtedly the isolation and generation of pluripotent stem cells, which will be the main focus of the remainder of the text.

Figure 1: Varying degrees of stem cell potency. Left: The fertilized egg (totipotent) develops into a 300-cell structure, the blastocyst, which contains embryonic stem cells (ES cells) at the inner cell mass (ICM). ES cells are pluripotent and can thus give rise to all cell types in our body, including adult stem cells, which range from multipotent to unipotent. Right: An alternative route to obtain pluripotent stem cells is the generation of induced pluripotent stem cells (iPS cells) from patients. Cell types obtained by differentiation of either ES cell (Left) or iPS cells (Right) can then be studied in the dish or used for transplantation into patients. Figure drawn by Hannah Somhegyi.

Martin Evans (Nobel Prize, 2007) and Matt Kauffman were the first to identify, isolate and successfully culture ES cells using mouse blastocysts in 1981 []. This discovery opened the doors to the creation of murine genetic models, which are mice that have had one or several of their genes deleted or otherwise modified to study their function in disease []. This is possible because scientists can modify the genome of a mouse in its ES cells and then inject those modified cells into mouse blastocysts. This means that when the blastocyst develops into an adult mouse, every cell its body will have the modification of interest.

The desire to use stem cells unique properties in medicine was greatly intensified when James Thomson and collaborators first isolated ES cells from human blastocysts []. For the first time, scientists could, in theory, generate all the building blocks of our body in unlimited amounts. It was possible to have cell types for testing new therapeutics and perhaps even new transplantation methods that were previously not possible. Yet, destroying human embryos to isolate cells presented ethical and technical hurdles. How could one circumvent that procedure? Sir John Gurdon showed in the early 1960s that, contrary to the prevalent belief back then, cells are not locked in their differentiation state and can be reverted to a more primitive state with a higher developmental potential. He demonstrated this principle by injecting the nucleus of a differentiated frog cell into an egg cell from which the nucleus had been removed. (This is commonly known as reproductive cloning, which was used to generate Dolly the Sheep.) When allowed to develop, this egg gave rise to a fertile adult frog, proving that differentiated cells retain the information required to give rise to all cell types in the body. More than forty years later, Shinya Yamanaka and colleagues shocked the world when they were able to convert skin cells called fibroblasts into pluripotent stem cells by altering the expression of just four genes []. This represented the birth of induced pluripotent stem cells, or iPS cells (see Figure 1, right column). The enormous importance of these findings is hard to overstate, and is perhaps best illustrated by the fact that, merely six years later, Gurdon and Yamanaka shared the Nobel Prize in Physiology or Medicine 2012 [].

Since the generation of iPS cells was first reported, the stem cell eld has expanded at an unparalleled pace. Today, these cells are the hope of personalized medicine, as they allow one to capture the unique genome of each individual in a cell type that can be used to generate, in principle, all cell types in our body, as illustrated on the right panel of Figure 1. The replacement of diseased tissues or organs without facing the barrier of immune rejection due to donor incompatibility thus becomes approachable in this era of iPS cells and is the object of intense research [].

The first proof-of-principle study showing that iPS cells can potentially be used to correct genetic diseases was carried out in the laboratory of Rudolf Jaenisch. In brief, tail tip cells from mice with a mutation causing sickle cell anemia were harvested and reprogrammed into iPS cells. The mutation was then corrected in these iPS cells, which were then differentiated into blood progenitor cells and transplanted back into the original mice, curing them []. Even though iPS cells have been found not to completely match ES cells in some instances, detailed studies have failed to find consistent differences between iPS and ES cells []. This similarity, together with the constant improvements in the efficiency and robustness of generating iPS cells, provides bright prospects for the future of stem cell research and stem cell-based treatments for degenerative diseases unapproachable with more conventional methods.

Leonardo M. R. Ferreira is a graduate student in Harvard Universitys Department of Molecular and Cellular Biology

[] Stem Cell Basics: http://stemcells.nih.gov/info/basics/Pages/Default.aspx

[] Becker, A. J., McCulloch, E.A., Till, J.E. Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells. Nature 1963. 197: 452-4

[] Siminovitch, L., McCulloch, E.A., Till, J.E. The distribution of colony-forming cells among spleen colonies. J Cell Comp Physiol 1963, 62(3): 327-336

[] Evans, M. J. and Kaufman, M. Establishment in culture of pluripotential stem cells from mouse embryos. Nature 1981, 292: 151156

[] Simmons, D. The Use of Animal Models in Studying Genetic Disease: Transgenesis and Induced Mutation. Nature Education 2008,1(1):70

[] Thomson, J. A. et al. Embryonic stem cell lines derived from human blastocysts. Science 1998, 282(5391): 1145-1147

[] Takahashi, K. and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006. 126(4): 663-76

[] The Nobel Prize in Physiology or Medicine 2012:

[] Ferreira, L.M.R. and Mostajo-Radji, M.A. How induced pluripotent stem cells are redefining personalized medicine. Gene 2013. 520(1): 1-6 [] Hanna J. et al. Treatment of sickle cell anemia mouse model with iPS cells generated from autologous skin. Science 2007. 318: 1920-1923

[] Yee,J.Turning Somatic Cells into Pluripotent Stem Cells.Nature Education 2010.3(9):25

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RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells – India Education Diary

Posted: December 27, 2022 at 12:40 am

RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells  India Education Diary

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RUDN Physician And Russian Scientists Investigate Long-term Effects Of Treating Diabetic Ulcers With Stem Cells - India Education Diary

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Stem Cell Basics | STEM Cell Information – National Institutes of Health

Posted: December 2, 2022 at 12:48 am

I. Introduction: What are stem cells, and why are they important?

Stem cells have the remarkable potential to renew themselves. They can develop into many different cell types in the body during early life and growth. Researchers study many different types of stem cells. There are several main categories: the pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) and nonembryonic or somatic stem cells (commonly called adult stem cells). Pluripotent stem cells have the ability to differentiate into all of the cells of the adult body. Adult stem cells are found in a tissue or organ and can differentiate to yield the specialized cell types of that tissue or organ.

Pluripotent stem cells

Early mammalian embryos at the blastocyst stage contain two types of cells cells of the inner cell mass, and cells of the trophectoderm. The trophectodermal cells contribute to the placenta. The inner cell mass will ultimately develop into the specialized cell types, tissues, and organs of the entire body of the organism. Previous work with mouse embryos led to the development of a method in 1998 to derive stem cells from the inner cell mass of preimplantation human embryos and to grow human embryonic stem cells (hESCs) in the laboratory. In 2006, researchers identified conditions that would allow some mature human adult cells to be reprogrammed into an embryonic stem cell-like state. Those reprogramed stem cells are called induced pluripotent stem cells (iPSCs).

Adult stem cells

Throughout the life of the organism, populations of adult stem cells serve as an internal repair system that generates replacements for cells that are lost through normal wear and tear, injury, or disease. Adult stem cells have been identified in many organs and tissues and are generally associated with specific anatomical locations. These stem cells may remain quiescent (non-dividing) for long periods of time until they are activated by a normal need for more cells to maintain and repair tissues.

Stem cells have unique abilities to self-renew and to recreate functional tissues.

Stem cells have the ability to self-renew.

Unlike muscle cells, blood cells, or nerve cellswhich do not normally replicate stem cells may replicate many times. When a stem cell divides, the resulting two daughter cells may be: 1) both stem cells, 2) a stem cell and a more differentiated cell, or 3) both more differentiated cells. What controls the balance between these types of divisions to maintain stem cells at an appropriate level within a given tissue is not yet well known.

Discovering the mechanism behind self-renewal may make it possible to understand how cell fate (stem vs. non-stem) is regulated during normal embryonic development and post-natally, or misregulated as during aging, or even in the development of cancer. Such information may also enable scientists to grow stem cells more efficiently in the laboratory. The specific factors and conditions that allow pluripotent stem cells to remain undifferentiated are of great interest to scientists. It has taken many years of trial and error to learn to derive and maintain pluripotent stem cells in the laboratory without the cells spontaneously differentiating into specific cell types.

Stem cells have the ability to recreate functional tissues.

Pluripotent stem cells are undifferentiated; they do not have any tissue-specific characteristics (such as morphology or gene expression pattern) that allow them to perform specialized functions. Yet they can give rise to all of the differentiated cells in the body, such as heart muscle cells, blood cells, and nerve cells. On the other hand, adult stem cells differentiate to yield the specialized cell types of the tissue or organ in which they reside, and may have defining morphological features and patterns of gene expression reflective of that tissue.

Different types of stems cells have varying degrees of potency; that is, the number of different cell types that they can form. While differentiating, the cell usually goes through several stages, becoming more specialized at each step. Scientists are beginning to understand the signals that trigger each step of the differentiation process. Signals for cell differentiation include factors secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment.

How are stem cells grown in the laboratory?

Growing cells in the laboratory is known as cell culture. Stem cells can proliferate in laboratory environments in a culture dish that contains a nutrient broth known as culture medium (which is optimized for growing different types of stem cells). Most stem cells attach, divide, and spread over the surface of the dish.

The culture dish becomes crowded as the cells divide, so they need to be re-plated in the process of subculturing, which is repeated periodically many times over many months. Each cycle of subculturing is referred to as a passage. The original cells can yield millions of stem cells. At any stage in the process, batches of cells can be frozen and shipped to other laboratories for further culture and experimentation.

How do you reprogram regular cells to make iPSCs?

Differentiated cells, such as skin cells, can be reprogrammed back into a pluripotent state. Reprogramming is achieved over several weeks by forced expression of genes that are known to be master regulators of pluripotency. At the end of this process, these master regulators will remodel the expression of an entire network of genes. Features of differentiated cells will be replaced by those associated with the pluripotent state, essentially reversing the developmental process.

How are stem cells stimulated to differentiate?

As long as the pluripotent stem cells are grown in culture under appropriate conditions, they can remain undifferentiated. To generate cultures of specific types of differentiated cells, scientists may change the chemical composition of the culture medium, alter the surface of the culture dish, or modify the cells by forcing the expression of specific genes. Through years of experimentation, scientists have established some basic protocols, or recipes, for the differentiation of pluripotent stem cells into some specific cell types (see Figure 1 below).

What laboratory tests are used to identify stem cells?

At various points during the process of generating stem cell lines, scientists test the cells to see whether they exhibit the fundamental properties that make them stem cells. These tests may include:

Given their unique regenerative abilities, there are many ways in which human stem cells are being used in biomedical research and therapeutics development.

Understanding the biology of disease and testing drugs

Scientists can use stem cells to learn about human biology and for the development of therapeutics. A better understanding of the genetic and molecular signals that regulate cell division, specialization, and differentiation in stem cells can yield information about how diseases arise and suggest new strategies for therapy. Scientists can use iPSCs made from a patient and differentiate those iPSCs to create organoids (small models of organs) or tissue chips for studying diseased cells and testing drugs, with personalized results.

Cell-based therapies

An important potential application is the generation of cells and tissues for cell-based therapies, also called tissue engineering. The current need for transplantable tissues and organs far outweighs the available supply. Stem cells offer the possibility of a renewable source. There is typically a very small number of adult stem cells in each tissue, and once removed from the body, their capacity to divide is limited, making generation of large quantities of adult stem cells for therapies difficult. In contrast, pluripotent stem cells are less limited by starting material and renewal potential.

To realize the promise of stem cell therapies in diseases, scientists must be able to manipulate stem cells so that they possess the necessary characteristics for successful differentiation, transplantation, and engraftment. Scientists must also develop procedures for the administration of stem cell populations, along with the induction of vascularization (supplying blood vessels), for the regeneration and repair of three-dimensional solid tissues.

To be useful for transplant purposes, stem cells must be reproducibly made to:

While stem cells offer exciting promise for future therapies, significant technical hurdles remain that will likely only be overcome through years of intensive research.

Note: Currently, the only stem cell-based products that are approved for use by the U.S. Food and Drug Administration (FDA) for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood. These products are approved for limited use in patients with disorders that affect the body system that is involved in the production of blood (called the hematopoietic system). TheseFDA-approved stem cell products are listed on the FDA website. Bone marrow also is used for these treatments but is generally not regulated by the FDA for this use. The FDA recommends that people considering stem cell treatments make sure that the treatment is either FDA-approved or being studied under an Investigational New Drug Application (IND), which is a clinical investigation plan submitted and allowed to proceed by the FDA.

NIH conducts and funds basic, translational, and clinical research with a range of different types of stem cells. NIH-supported research with human pluripotent stem cells is conducted under the terms of theNIH Guidelines for Human Stem Cell Research. NIH awards are listed in various categories of stem cell research through theNIH Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC). NIH also supports a major adult stem cell and iPSC research initiative through theRegenerative Medicine Innovation Project.

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Donate Stem Cells | Bone Marrow Donation – American Cancer Society

Posted: November 24, 2022 at 12:35 am

People usually volunteer to donate stem cells for an allogeneic transplant either because they have a loved one or friend who needs a match or because they want to help people. Some people give their stem cells so they can get them back later if they need an autologous transplant.

Medical guidelines are in place to protect the health of potential donors, as well as the health of bone marrow and stem cell transplant patients. Many factors can affect if a person is eligible to register as a donor.

People, including cancer survivors,who want to donate stem cells or join a volunteer registry can check the eligibility list available through the registry. They can also speak with a health care provider or contact the National Marrow Donor Program to find the nearest donor center. Potential donors are asked questions to make sure they are healthy enough to donate and dont pose a risk of infection to the recipient. For more information about donor eligibility guidelines, contact Be the Match or the donor center in your area.

Be the Match (formerly the National Marrow Donor Program)Toll-free number: 1-800-MARROW-2 (1-800-627-7692)Website: http://www.bethematch.org

A simple blood test is done to learn the potential donors HLA type. There may be a one-time, tax-deductible fee of about $75 to $100 for this test. People who join a volunteer donor registry will most likely have their tissue type kept on file until they reach age 60.

Pregnant women who want to donate their babys cord blood should make arrangements for it early in the pregnancy, at least before the third trimester. Donation is safe, free, and does not affect the birth process.

If a possible stem cell donor is found to be a good match for a recipient, steps are taken to teach the donor about the transplant process and make sure they are making an informed decision. If a person decides to donate, a consent form must be signed after the risks of donating are fully discussed. The donor is not pressured to take part. Its always a choice.

If a person decides to donate, a medical exam and blood tests will be done to make sure they are in good health.

Stem cells may be collected from these 3 different sources:

Each method of collection is explained here.

This process is often called bone marrow harvest. Its done in an operating room, while the donor is under general anesthesia (given medicine to put them into a deep sleep so they dont feel pain). The marrow cells are taken from the back of the pelvic (hip) bone. The donor lies face down, and a large needle is put through the skin and into the back of the hip bone. Its pushed through the bone to the center and the thick, liquid marrow is pulled out through the needle. This is repeated several times until enough marrow has been taken out (harvested). The amount taken depends on the donors weight. Often, about 10% of the donors marrow, or about 2 pints, are collected. This takes about 1 to 2 hours. The body will replace these cells within 4 to 6 weeks. If blood was taken from the donor before the marrow donation, its often given back to the donor at this time.

After the bone marrow is harvested, the donor is taken to the recovery room while the anesthesia wears off. The donor may then be taken to a hospital room and watched until fully alert and able to eat and drink. In most cases, the donor is able to leave the hospital within a few hours or by the next morning.

The donor may have soreness, bruising, and aching at the back of the hips and lower back for a few days. Over-the-counter pain medications or nonsteroidal anti-inflammatory drugs are helpful. Some people may feel tired or weak, and have trouble walking for a few days. The donor might be told to take iron supplements until the number of red blood cells returns to normal. Most donors get back to their usual activities in 2 to 3 days. But it could take 2 or 3 weeks before they feel completely back to normal.

There arent many risks for donors and serious complications are rare. But bone marrow donation is a surgical procedure. Rare complications could include anesthesia reactions, infection, nerve or muscle damage, transfusion reactions (if a blood transfusion of someone elses blood is needed this doesnt happen if you get your own blood), or injury at the needle insertion sites. Problems such as sore throat or nausea may be caused by anesthesia.

Allogeneic stem cell donors do not have to pay for the harvesting because the recipients insurance company usually covers the cost. Even so, be sure to ask about insurance coverage before you decide to have the bone marrow harvest done.

Once the cells are collected, they are filtered through fine mesh screens. This prevents bone or fat particles from being given to the recipient. For an allogeneic or syngeneic transplant, the cells may be given to the recipient through a vein soon after they are harvested. Sometimes theyre frozen, for example, if the donor lives far away from the recipient.

For several days before starting the donation process, the donor is given a daily injection (shot) of a drug that causes the bone marrow to make and release a lot of stem cells into the blood. Filgrastim can cause some side effects, the most common being bone pain and headaches. These may be helped by over-the-counter pain medications or nonsteroidal anti-inflammatory drugs. Nausea, sleeping problems, low-grade (mild) fevers, and tiredness are other possible effects. These go away once the injections are finished and collection is completed.

After the shots, blood is removed through a catheter (a thin, flexible plastic tube) thats put in a large vein in the arm. Its then cycled through a machine that separates the stem cells from the other blood cells. The stem cells are kept while the rest of the blood is returned to the donor, often through the same catheter. (In some cases, a catheter may be put in each arm one takes out blood and the other puts it back.) This process is called apheresis. It takes about 2 to 4 hours and is done as an outpatient procedure. Often the process needs to be repeated daily for a few days, until enough stem cells have been collected.

Possible side effects of the catheter can include trouble placing the catheter in the vein, blockage of the catheter, or infection of the catheter or at the area where it enters the vein. Blood clots are another possible side effect. During the apheresis procedure, donors may have problems caused by low calcium levels from the anti-coagulant drug used to keep the blood from clotting in the machine. These can include feeling lightheaded or tingly, and having chills or muscle cramps. These go away after donation is complete, but may be treated by giving the donor calcium supplements.

The process of donating cells for yourself (autologous stem cell donation) is pretty much the same as when someone donates them for someone else (allogeneic donation). Its just that in autologous stem cell donation the donor is also the recipient, giving stem cells for their own use later on. For some people, there are a few differences. For instance, sometimes chemotherapy (chemo) is given before the growth factor drug is used to tell the body to make stem cells. Also, sometimes it can be hard to get enough stem cells from a person with cancer. Even after several days of apheresis, there may not be enough for the transplant. This is more likely to be a problem if the patient has had certain kinds of chemo in the past, or if they have an illness that affects their bone marrow.

Cord blood is the blood thats left in the placenta and umbilical cord after a baby is born. Collecting it does not pose any health risk to the infant or the mother. Cord blood transplants use blood that would otherwise be thrown away. After the umbilical cord is clamped and cut, the placenta and umbilical cord are cleaned. The cord blood is put into a sterile container, mixed with a preservative, and frozen until needed.

Some parents choose to donate their infants cord blood to a public blood bank, so that it may be used by anyone who needs it. Many hospitals collect cord blood for donation, which makes it easier for parents to donate. Parents can donate their newborns cord blood to volunteer or public cord blood banks at no cost. For more about donating your newborns cord blood, call 1-800-MARROW2 (1-800-627-7692) or visit Be the Match.

Other parents store their newborns cord blood in private cord blood banks just in case the child or a close relative needs it someday. If you want to donate or bank (save) your childs cord blood, youll need to arrange it before the baby is born. Some banks require you to set it up before the 28th week of pregnancy, although others accept later setups. Among other things, youll be asked to answer health questions and sign a consent form.

Parents may want to bank their childs cord blood if the family has a history of diseases that may benefit from stem cell transplant. There are several private companies offer this service. But here are some things to think about:

More information on private family cord blood banking can be found at the Parents Guide to Cord Blood Foundation. You can visit their website at http://www.parentsguidecordblood.org.

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Neural stem cell – Wikipedia

Posted: November 24, 2022 at 12:35 am

Precursor cells of neurons and glia during embryonic development

Neural stem cells (NSCs) are self-renewing, multipotent cells that firstly generate the radial glial progenitor cells that generate the neurons and glia of the nervous system of all animals during embryonic development.[1] Some neural progenitor stem cells persist in highly restricted regions in the adult vertebrate brain and continue to produce neurons throughout life. Differences in the size of the central nervous system are among the most important distinctions between the species and thus mutations in the genes that regulate the size of the neural stem cell compartment are among the most important drivers of vertebrate evolution. [2]

Stem cells are characterized by their capacity to differentiate into multiple cell types.[3] They undergo symmetric or asymmetric cell division into two daughter cells. In symmetric cell division, both daughter cells are also stem cells. In asymmetric division, a stem cell produces one stem cell and one specialized cell.[4] NSCs primarily differentiate into neurons, astrocytes, and oligodendrocytes.

In the adult mammalian brain, the subgranular zone in the hippocampal dentate gyrus, the subventricular zone around the lateral ventricles, and the hypothalamus (precisely in the dorsal 1, 2 region and the "hypothalamic proliferative region, located in the adjacent median eminence) have been reported to contain neural stem cells.[5]

There are two basic types of stem cell: adult stem cells, which are limited in their ability to differentiate, and embryonic stem cells (ESCs), which are pluripotent and have the capability of differentiating into any cell type.[3]

Neural stem cells are more specialized than ESCs because they only generate radial glial cells that give rise to the neurons and to glia of the central nervous system (CNS).[4] During the embryonic development of vertebrates, NSCs transition into radial glial cells (RGCs) also known as radial glial progenitor cells, (RGPs) and reside in a transient zone called the ventricular zone (VZ).[1][6] Neurons are generated in large numbers by (RGPs) during a specific period of embryonic development through the process of neurogenesis, and continue to be generated in adult life in restricted regions of the adult brain.[7] Adult NSCs differentiate into new neurons within the adult subventricular zone (SVZ), a remnant of the embryonic germinal neuroepithelium, as well as the dentate gyrus of the hippocampus.[7]

Adult NSCs were first isolated from mouse striatum in the early 1990s. They are capable of forming multipotent neurospheres when cultured in vitro. Neurospheres can produce self-renewing and proliferating specialized cells. These neurospheres can differentiate to form the specified neurons, glial cells, and oligodendrocytes.[7] In previous studies, cultured neurospheres have been transplanted into the brains of immunodeficient neonatal mice and have shown engraftment, proliferation, and neural differentiation.[7]

NSCs are stimulated to begin differentiation via exogenous cues from the microenvironment, or stem cell niche. Some neural cells are migrated from the SVZ along the rostral migratory stream which contains a marrow-like structure with ependymal cells and astrocytes when stimulated. The ependymal cells and astrocytes form glial tubes used by migrating neuroblasts. The astrocytes in the tubes provide support for the migrating cells as well as insulation from electrical and chemical signals released from surrounding cells. The astrocytes are the primary precursors for rapid cell amplification. The neuroblasts form tight chains and migrate towards the specified site of cell damage to repair or replace neural cells. One example is a neuroblast migrating towards the olfactory bulb to differentiate into periglomercular or granule neurons which have a radial migration pattern rather than a tangential one.[8]

Neural stem cell proliferation declines as a consequence of aging.[9] Various approaches have been taken to counteract this age-related decline.[10] Because FOX proteins regulate neural stem cell homeostasis,[11] FOX proteins have been used to protect neural stem cells by inhibiting Wnt signaling.[12]

Epidermal growth factor (EGF) and fibroblast growth factor (FGF) are mitogens that promote neural progenitor and stem cell growth in vitro, though other factors synthesized by the neural progenitor and stem cell populations are also required for optimal growth.[13] It is hypothesized that neurogenesis in the adult brain originates from NSCs. The origin and identity of NSCs in the adult brain remain to be defined.

The most widely accepted model of an adult NSC is a radial, glial fibrillary acidic protein-positive cell. Quiescent stem cells are Type B that are able to remain in the quiescent state due to the renewable tissue provided by the specific niches composed of blood vessels, astrocytes, microglia, ependymal cells, and extracellular matrix present within the brain. These niches provide nourishment, structural support, and protection for the stem cells until they are activated by external stimuli. Once activated, the Type B cells develop into Type C cells, active proliferating intermediate cells, which then divide into neuroblasts consisting of Type A cells. The undifferentiated neuroblasts form chains that migrate and develop into mature neurons. In the olfactory bulb, they mature into GABAergic granule neurons, while in the hippocampus they mature into dentate granule cells.[14]

Epigenetic modifications are important regulators of gene expression in differentiating neural stem cells. Key epigenetic modifications include DNA cytosine methylation to form 5-methylcytosine and 5-methylcytosine demethylation.[15][16] These types of modification are critical for cell fate determination in the developing and adult mammalian brain.

DNA cytosine methylation is catalyzed by DNA methyltransferases (DNMTs). Methylcytosine demethylation is catalyzed in several distinct steps by TET enzymes that carry out oxidative reactions (e.g. 5-methylcytosine to 5-hydroxymethylcytosine) and enzymes of the DNA base excision repair (BER) pathway.[15]

NSCs have an important role during development producing the enormous diversity of neurons, astrocytes and oligodendrocytes in the developing CNS. They also have important role in adult animals, for instance in learning and hippocampal plasticity in the adult mice in addition to supplying neurons to the olfactory bulb in mice.[7]

Notably the role of NSCs during diseases is now being elucidated by several research groups around the world. The responses during stroke, multiple sclerosis, and Parkinson's disease in animal models and humans is part of the current investigation. The results of this ongoing investigation may have future applications to treat human neurological diseases.[7]

Neural stem cells have been shown to engage in migration and replacement of dying neurons in classical experiments performed by Sanjay Magavi and Jeffrey Macklis.[17] Using a laser-induced damage of cortical layers, Magavi showed that SVZ neural progenitors expressing Doublecortin, a critical molecule for migration of neuroblasts, migrated long distances to the area of damage and differentiated into mature neurons expressing NeuN marker. In addition, Masato Nakafuku's group from Japan showed for the first time the role of hippocampal stem cells during stroke in mice.[18] These results demonstrated that NSCs can engage in the adult brain as a result of injury. Furthermore, in 2004 Evan Y. Snyder's group showed that NSCs migrate to brain tumors in a directed fashion. Jaime Imitola, M.D and colleagues from Harvard demonstrated for the first time, a molecular mechanism for the responses of NSCs to injury. They showed that chemokines released during injury such as SDF-1a were responsible for the directed migration of human and mouse NSCs to areas of injury in mice.[19] Since then other molecules have been found to participate in the responses of NSCs to injury. All these results have been widely reproduced and expanded by other investigators joining the classical work of Richard L. Sidman in autoradiography to visualize neurogenesis during development, and neurogenesis in the adult by Joseph Altman in the 1960s, as evidence of the responses of adult NSCs activities and neurogenesis during homeostasis and injury.

The search for additional mechanisms that operate in the injury environment and how they influence the responses of NSCs during acute and chronic disease is matter of intense research.[20]

Cell death is a characteristic of acute CNS disorders as well as neurodegenerative disease. The loss of cells is amplified by the lack of regenerative abilities for cell replacement and repair in the CNS. One way to circumvent this is to use cell replacement therapy via regenerative NSCs. NSCs can be cultured in vitro as neurospheres. These neurospheres are composed of neural stem cells and progenitors (NSPCs) with growth factors such as EGF and FGF. The withdrawal of these growth factors activate differentiation into neurons, astrocytes, or oligodendrocytes which can be transplanted within the brain at the site of injury. The benefits of this therapeutic approach have been examined in Parkinson's disease, Huntington's disease, and multiple sclerosis. NSPCs induce neural repair via intrinsic properties of neuroprotection and immunomodulation. Some possible routes of transplantation include intracerebral transplantation and xenotransplantation.[21][22]

An alternative therapeutic approach to the transplantation of NSPCs is the pharmacological activation of endogenous NSPCs (eNSPCs). Activated eNSPCs produce neurotrophic factors, several treatments that activate a pathway that involves the phosphorylation of STAT3 on the serine residue and subsequent elevation of Hes3 expression (STAT3-Ser/Hes3 Signaling Axis) oppose neuronal death and disease progression in models of neurological disorder.[23][24]

Human midbrain-derived neural progenitor cells (hmNPCs) have the ability to differentiate down multiple neural cell lineages that lead to neurospheres as well as multiple neural phenotypes. The hmNPC can be used to develop a 3D in vitro model of the human CNS. There are two ways to culture the hmNPCs, the adherent monolayer and the neurosphere culture systems. The neurosphere culture system has previously been used to isolate and expand CNS stem cells by its ability to aggregate and proliferate hmNPCs under serum-free media conditions as well as with the presence of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF2). Initially, the hmNPCs were isolated and expanded before performing a 2D differentiation which was used to produce a single-cell suspension. This single-cell suspension helped achieve a homogenous 3D structure of uniform aggregate size. The 3D aggregation formed neurospheres which was used to form an in vitro 3D CNS model.[25]

Traumatic brain injury (TBI) can deform the brain tissue, leading to necrosis primary damage which can then cascade and activate secondary damage such as excitotoxicity, inflammation, ischemia, and the breakdown of the blood-brain-barrier. Damage can escalate and eventually lead to apoptosis or cell death. Current treatments focus on preventing further damage by stabilizing bleeding, decreasing intracranial pressure and inflammation, and inhibiting pro-apoptotic cascades. In order to repair TBI damage, an upcoming therapeutic option involves the use of NSCs derived from the embryonic peri-ventricular region. Stem cells can be cultured in a favorable 3-dimensional, low cytotoxic environment, a hydrogel, that will increase NSC survival when injected into TBI patients. The intracerebrally injected, primed NSCs were seen to migrate to damaged tissue and differentiate into oligodendrocytes or neuronal cells that secreted neuroprotective factors.[26][27]

Galectin-1 is expressed in adult NSCs and has been shown to have a physiological role in the treatment of neurological disorders in animal models. There are two approaches to using NSCs as a therapeutic treatment: (1) stimulate intrinsic NSCs to promote proliferation in order to replace injured tissue, and (2) transplant NSCs into the damaged brain area in order to allow the NSCs to restore the tissue. Lentivirus vectors were used to infect human NSCs (hNSCs) with Galectin-1 which were later transplanted into the damaged tissue. The hGal-1-hNSCs induced better and faster brain recovery of the injured tissue as well as a reduction in motor and sensory deficits as compared to only hNSC transplantation.[8]

Neural stem cells are routinely studied in vitro using a method referred to as the Neurosphere Assay (or Neurosphere culture system), first developed by Reynolds and Weiss.[28] Neurospheres are intrinsically heterogeneous cellular entities almost entirely formed by a small fraction (1 to 5%) of slowly dividing neural stem cells and by their progeny, a population of fast-dividing nestin-positive progenitor cells.[28][29][30] The total number of these progenitors determines the size of a neurosphere and, as a result, disparities in sphere size within different neurosphere populations may reflect alterations in the proliferation, survival and/or differentiation status of their neural progenitors. Indeed, it has been reported that loss of 1-integrin in a neurosphere culture does not significantly affect the capacity of 1-integrin deficient stem cells to form new neurospheres, but it influences the size of the neurosphere: 1-integrin deficient neurospheres were overall smaller due to increased cell death and reduced proliferation.[31]

While the Neurosphere Assay has been the method of choice for isolation, expansion and even the enumeration of neural stem and progenitor cells, several recent publications have highlighted some of the limitations of the neurosphere culture system as a method for determining neural stem cell frequencies.[32] In collaboration with Reynolds, STEMCELL Technologies has developed a collagen-based assay, called the Neural Colony-Forming Cell (NCFC) Assay, for the quantification of neural stem cells. Importantly, this assay allows discrimination between neural stem and progenitor cells.[33]

The first evidence that neurogenesis occurs in certain regions of the adult mammalian brain came from [3H]-thymidine labeling studies conducted by Altman and Das in 1965 which showed postnatal hippocampal neurogenesis in young rats.[34] In 1989, Sally Temple described multipotent, self-renewing progenitor and stem cells in the subventricular zone (SVZ) of the mouse brain.[35] In 1992, Brent A. Reynolds and Samuel Weiss were the first to isolate neural progenitor and stem cells from the adult striatal tissue, including the SVZ one of the neurogenic areas of adult mice brain tissue.[28] In the same year the team of Constance Cepko and Evan Y. Snyder were the first to isolate multipotent cells from the mouse cerebellum and stably transfected them with the oncogene v-myc.[36] This molecule is one of the genes widely used now to reprogram adult non-stem cells into pluripotent stem cells. Since then, neural progenitor and stem cells have been isolated from various areas of the adult central nervous system, including non-neurogenic areas, such as the spinal cord, and from various species including humans.[37][38]

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Stem Cells- Definition, Properties, Types, Uses, Challenges

Posted: November 6, 2022 at 1:50 am

Stem Cells Definition

Stem cells are unique cells present in the body that have the potential to differentiate into various cell types or divide indefinitely to produce other stem cells.

Figure: Stem Cell Renewal and Differentiation. Image Source: Maharaj Institute of Immune Regenerative Medicine.

All the stem cells found throughout all living systems have three important properties. These properties can be visualized in vitro by a process called clonogenic assays, where a single cell is assessed for its ability to differentiate.

The following are some properties of stem cells:

Figure: Techniques for generating embryonic stem cell cultures. Image Source: John Wiley & Sons, Inc. (Nico Heins et al.)

Depending on the source of the stem cells or where they are present, stem cells are divided into various types;

Figure: Human Embryonic Stem Cells Differentiation. Image created with biorender.com

Figure: Preliminary Evidence of Plasticity Among Nonhuman Adult Stem Cells. Image Source: NIH Stem Cell Information.

Figure: Progress in therapies based on iPSCs. Image Source: Nature Reviews Genetics (R. Grant Rowe & George Q. Daley).

Figure: Mesenchymal stem cells (MSCs). Image Source: PromoCell GmbH.

Some of the common and well-known examples of stem cell research are:

Stem cell research has been used in various areas because of their properties. Some of the common applications of stem cells research include;

Because of different ethical and other issues related to stem cell research, there are some limitations or challenges of stem cell research. Some of these are:

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Brothers from Karnataka, Prapul and Prajwal donated their stem cells, save two blood cancer patients – APN News

Posted: November 6, 2022 at 1:50 am

Brothers from Karnataka, Prapul and Prajwal donated their stem cells, save two blood cancer patients  APN News

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Getting These Stem Cells Treatments: Crippled Ronnie Coleman Gives a Positive Update on His Ability to Walk – EssentiallySports

Posted: October 21, 2022 at 2:49 am

Getting These Stem Cells Treatments: Crippled Ronnie Coleman Gives a Positive Update on His Ability to Walk  EssentiallySports

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Getting These Stem Cells Treatments: Crippled Ronnie Coleman Gives a Positive Update on His Ability to Walk - EssentiallySports

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Cornell Prof Explains Relevance of Creating Mouse Embryos from Stem Cells – Cornell University The Cornell Daily Sun

Posted: October 13, 2022 at 2:02 am

In August 2022, NIH researchers from the University of Cambridge successfully created a synthetic mouse embryo model using cultured mice stem cells. This project aimed at using stem cells to express specific genes that would lead to the development of these mouse stem cells into embryos.

Stem cells are undifferentiated cells that developed into specialized cells with specific functions.

Prof. John Schimenti, biomedical sciences, explained the processes involved in this project as well as its implications for the future of scientific research.

There are many different types of stem cells and the relevant type for these experiments are called embryonic stem cells. These are totally undifferentiated and in the right context, could make all cells in the body by giving rise to more differentiated cells, Schimenti said.

The stem cells are placed in a culture medium, which optimizes their growth by stimulating cell-to-cell communication. This communication is necessary because cells use signaling during embryonic development.

This system of cell communication as a means of embryonic development is similar to the process of natural embryonic development in mammalian pregnancies such as humans.

During fertilization, the fertilized eggs cells divide into an embryo as it implants into the uterus.

Scientists had applied this knowledge by taking embryonic stem cells extracted in the lab and combining them with these early embryos. They were then placed in the uterus of a mouse subject and the resulting fetus contained cells that were partly, if not entirely, from the stem cells.

While the fetus develops, the mother starts to grow a new organ called the placenta, which supplies the fetus with the necessary nutrients as well as oxygen and glucose. The placenta guides the development of organs, acts as an immunological barrier to protect the fetus against infections, and synthesizes fatty acids and cholesterol, among other critical functions.

However, scientists found it challenging to mimic this natural environment in a petri dish because there was no placenta, which would have normally supplied the right balance of nutrients to the developing embryo.

To direct the development of the synthetic embryo, the researchers in this project started with embryonic stem cells that were completely undifferentiated. They then differentiated some of them into two different cell types by adding the corresponding developed cells.

The first group of differentiated cells would ultimately form the placenta and the other would become the yolk sac, a membranous structure attached to an embryo where the embryos first blood cells are made.

There are three different types of cells present: the unadulterated embryonic stem cells and the two partially differentiated helper tissues. They are mixed together after doing experiments to figure out the right ratios of factors like gas and nutrient levels, Schimenti said.

The project, starting in 2012, culminated in a synthetic embryo with a semi-functioning brain and heart. The organs were semi functioning because while they did work, they were not enough to independently sustain life.

This outcome significantly adds to the understanding of not only stem cells but the science of embryonic development because it allows scientists to experiment with embryonic development in real time. The University provides a unique opportunity to engage more with these concepts through its initiatives for stem cell research such as the Ansary Center for Stem Cell Therapeutics and the later established Cornell Stem Cell Program.

Moving forward with this breakthrough, researchers at the University continue to refine the different aspects of stem cell research by pushing development further and improving the efficiency of the organs being developed.

Despite this scientific breakthrough, there is still more to contribute in the study of the relationship between stem cells and regenerative medicine.

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