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Stem Cell Types And Their Use In Internal Stem Cell Therapeutics

Introduction

This short paper will focus on stem cell therapeutics where stem cells are injected into the patient, as opposed to other stem cell-based therapeutics where the cells, or their products (such as proteins released from the stem cell) are applied topically to the patient. As injectables, stem cells have been demonstrated to be the most important therapeutic for many diseases and conditions because of three important characteristics that they possess. First, stem cells are unspecialized cells that can replenish their numbers for long periods through cell division. Second, after receiving certain chemical signals, they can differentiate, or transform into specialized cells with specific functions, such as a heart cell or nerve cell.  Third, and research and clinical practice suggests this aspect of stem cells may be their most important, stem cells have been shown to release and respond to a number of tissue regenerating proteins, including growth factors and cytokines. These three important characteristics distinguish stem cells from other cells in the body that do not possess these characteristics and therefore cannot be used in cellular therapeutics nearly as effectively as can the stem cells.

2.    Classification Of Stem Cell Type

Stem cells are often classified by the extent to which they can differentiate into different mature cell types, (but this classification does not specify what the cell types are able to release and respond to as signaling molecules):

    A. Totipotent stem cells can differentiate into any cell type in the adult body, and into the placenta to nourishe the embryo. A fertilized egg is a type of Totipotent stem cell. Cells produced in the first few divisions of the fertilized egg are also Totipotent.

    B. Pluripotent stem cells are descendants of the Totipotent stem cells of the embryo. These cells, which develop about four days after fertilization, can differentiate into any cell type, except for Totipotent stem cells and the cells of the placenta.

    C. Multipotent stem cells are descendants of Pluripotent stem cells and antecedents of specialized cells in particular tissues. For example, hematopoietic stem cells, found primarily in the bone marrow, give rise to all of the cells found in the blood, including red blood cells, white blood cells, and platelets. Another example are the neural stem cells that can differentiate into nerve cells and neural support cells called Glia.

    D. Progenitor cells (or Unipotent stem cells) can produce only one cell type. As an example, Erythroid Progenitor cells differentiate into only red blood cells. At the end of the long chain of cell divisions are “terminally differentiated” cells, such as a liver cell or lung cell, that are permanently committed to specific functions. These cells stay committed to their functions for the life of the organism or until a tumor develops. In the case of a tumor, the cells differentiate, or return to a less mature state. Research continues on both adult and embryonic stem cells to determine the characteristics and potential of both to cure disease.

Stem cells is a term used to describe all cells that can give rise to cells of multiple tissue types. However, there are different types of stems cells. Totipotent cells, like the cells of a fertilized egg in the first few days after fertilization, can give rise to a fully functional organism. During normal development, the Totipotent cells become more specialized and are considered Pluripotent, meaning that they can give rise to every cell type in the body, but will not give rise to the placenta or supporting tissues necessary for fetal development. Because their potential is not total, they are not Totipotent and they are not embryos. Pluripotent stem cells undergo further specialization into stem cells committed to generating cells that are specialized for a particular function. Multipotent cells can give rise to the cell types found in the tissue from which they were derived, such as blood stem cells that give rise only to red blood cells, white blood cells and platelets, or skin stem cells that give rise only to the various types of skin cells.

3.    Stem Cells Used For Cell Therapy

Stem cell therapy can be defined as a group of new techniques and technologies that rely on replacing diseased or dysfunctional cells with healthy, functioning cells, or replacing the molecules that the transplanted stem cells normally release into the area of tissue that is the recipient of the therapy. These new techniques are being applied to a wide range of human diseases, including many types of cancer, neurological diseases such as Parkinson’s,  Lou Gehrig’s disease, multiple schlerosis, spinal cord injuries, and diabetes. Further, replacing dysfunctional cells in the retina with new ones may someday cure even presently incurable neurodegenerative eye diseases such as glaucoma and macular degeneration. To understand how cell therapy works, we need to understand the role of cells in the body.

4. The function of cells

Cells are the basic building blocks of the human body. These tiny structures compose the skin, muscles, brain, bones and all of the internal organs. They also hold many of the keys to how our bodies function. Cells serve both a structural and a functional role in the body, performing an almost endless variety of actions to sustain the body’s tissues and organs underlying our mentation and our actions.

There are thousands of different specialized cell types in the adult body. All of these cells perform very specific functions for the tissue or organ in which they reside. Specialized cells in the heart muscle intrinsically “beat” rhythmically through the internal propagation of electrical signals are an example, while the cells of the pancreas produce and secrete insulin to help the body convert food to energy are another example. These two mature cells types have been differentiated, or dedicated, to performing their special tasks. Until recently, scientific evidence suggested that under normal conditions, once a cell has become specialized, it cannot be changed into a different type of cell.

Like the body itself, cells have a finite life span and will eventually die. Most of the cells in the body divide and duplicate throughout life, but some cells either don’t replenish themselves, or do so in such small numbers that they cannot replace themselves fast enough when faced with disease or injury where a large number of cells are destroyed at one instance.

5. How stem cell therapy works

While cells are indispensable in performing vital functions for the body, they can also exist outside the body using special scientific laboratory techniques. The cells can live and divide outside the body in “cultures,” utilizing special solutions in test tubes or Petrie dishes. This ability of certain cell types to live isolated from other cells under controlled conditions has allowed scientists to study them independently of the organ or system in which they are normally a part. Through the isolation and targeted manipulation of cells, biotech companies are finding ways to identify young, regenerating cells that can be used to replace damaged or dead cells in diseased or damaged organs. This therapy is similar to the process of organ transplant, however in stem cell therapy the treatment consists of the transplantation of cells rather than organs. The cells that have shown by far the most promise of supplying diseased and damaged organs with healthy new ones are called stem cells.

A key question in stem cell research and therapy is, do adult stem cells have the same therapeutic capability as embryonic stem cells? For many years, scientists have conducted studies to determine whether the stem cells in adult tissue have the same developmental capability as embryonic stem cells. The answer is yes and no, depending on the exact capability that is required for the therapeutic regimen. If we think of using stem cells for the conversion of the stem cell into a new, differentiated cell type (e.g. turning the stem cell into a heart cell) then the general consensus is that adult stem cells seem to be less versatile. However, if we think of stem cells as a means for repairing tissue through the release of “healing-molecules” into the damaged tissue, then adult stem cells may prove to be more effective then embryonic stem cells. Thus therapies for different types of conditions may require one or the other type of stem cell, or may require both the embryonic and the adult stem cell for proper reparation of the tissue.

6 The current use of cell therapies

Even though most of the work done in this field has been experimental in the USA, most scientists here find cell therapy so promising that they believe in a short time stem cell therapy will be routine. And while many  uses of stem cell therapy may be years away, there are a few forms of this technique that have already been in use for years. Bone marrow transplants are an example of cell therapy in which the stem cells in a donor’s marrow are used to replace the blood cells of the victims of leukemia and other cancers. Cell therapy is also being used in experiments to graft new skin cells to treat serious burn victims and diabetic ulcer wounds, and to grow new corneas for the sight-impaired. In all of these uses, the goal is for the healthy cells to become integrated into the body, acting as new cells that begin to function like the patient’s own cells and/or releasing growth factors and proteins into the damaged tissue to begin the regeneration process.

Thus far results of such experiments have exceeded expectations. In a recent advance, pancreatic cells grown from stem cells were implanted into the body of a diabetic and began to produce and release insulin. Results of the aforementioned therapies have caused great optimism in the scientific and medical communities. However, there are a number of scientific challenges that must be overcome before we can harness the complete power of stem cells for therapeutic use.

7. Current challenges of stem cell therapies

One of the first challenges to be overcome before stem cell therapies become commonplace is the difficulty of identifying stem cells in tissue cultures, which contain numerous types of confounding cells. While scientists are discovering new cell types almost every day, estimates are that thousands of human cell types exist. The process of identifying any desired type of stem cell will involve painstaking research. A second challenge, once stem cells are identified and isolated, the right biochemical solution must be developed to cause these progenitor cells to differentiate into the desired cell type, or to release their “healing-molecules.” This too will require a great deal of experimentation.

A third challenge arises when the cells are implanted into a person. The cells must be integrated into the patient’s own tissues and organs and function in concert with the body’s natural cells. Cardiac cells that beat in a cell culture, for example, may not beat in rhythm with a patient’s own heart cells. And neural stem cells injected into a damaged brain must become “wired into” the brain’s intricate network of cells and their connections in order to work properly.

Another challenge is the common phenomenon of tissue rejection. Similar to organ transplants, the body’s immune cells will recognize transplanted cells as “foreign,” setting off an immune reaction that could cause the transplant to fail and possibly endanger the patient. Yet another concern is the possible risk of inducing cancer. Cancers result  when cells lose their internal stop mechanisms and keep dividing when further proliferation is no longer desirable. Researchers must find a delicate balance between fostering the growth of new cells to replenish damaged tissues , while preventing them to overgrow and become cancerous. Recent studies suggest that these obstacles can be overcome and the power of stem cells can be fully harnessed.

Beyond the scientific and medical challenges, there are also ethical, social, financial and political issues affecting this new industry. One of the hardest issues for this industry to overcome is that patients are generally offered stem cell therapy after all other treatments have been exhausted, therefore limiting the chance for success. As is natural in the business world, success of stem cell therapy poses a serious financial threat to many other conventional treatments, and there are, therefore, powerful forces that using their power to minimize this industry’s successes and magnify its failures.

8. Some aspects of future stem cell therapy

Despite the many challenges facing scientists, most believe that stem cell therapy will revolutionize medicine. With the use of cell therapies, we may soon have dramatic cures for cancer, Parkinson’s, diabetes, kidney disease, multiple sclerosis, muscular degeneration, glaucoma, and many other diseases. Stem cell therapies have also shown great promise in helping to repair catastrophic wounds from burn and diabetic ulcers, spinal injuries, sickle cell anemia, and helping victims of paralysis regain movement. Stem cell therapies also provide the possibility that the human life span could be greatly extended due to the replenishment of tissues in aging organs. Perhaps one day we’ll be able to grow our own organs for transplantation from our own stem cells, eliminating the danger of organ rejection. While we will undoubtedly advance stem cell therapy one day to a full realization of its potential, in practice today as we speak, many humans around the world are experiencing better lives because of stem cell therapeutics in one form or another.

 

George Daley, MD, PhD, discusses new and advanced techniques for developing iPS cells.

In a proof-of-concept study, Mayo Clinic investigators have demonstrated that induced pluripotent stem (iPS) cells can be used to treat heart disease. iPS cells are stem cells converted from adult cells. In this study, the researchers reprogrammed ordinary fibroblasts, cells that contribute to scars such as those resulting from a heart attack, converting them into stem cells that fix heart damage caused by infarction. The findings appear in the current online issue of the journal Circulation. Timothy Nelson, MD, Ph.D., first author on the Mayo Clinic study, talks about the study and it’s findings.
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Pluripotent Stem Cells

Pluripotent cells of the early embryo originate all types of somatic cells and germ cells of adult organism. Pluripotent stems cell lines were derived from mammalian embryos and adult tissues using different techniques and from different sources. Despite different origin, all pluripotent stem cell lines demonstrate considerable similarity of the major biological properties. This book examines the fundamental mechanisms which regulate normal development of pluripotent cells into different lineage

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