Stem Cell in Medicine PDF

Stem cell in medicine Prepared by Dr. Heba Mohamed Lecturer of microbiology and immunology dpt. Aswan university Course outline Introduction to Stem cells : definition, types and potency. Stem cell niches and sources. Clinical application...

Stem cell in medicine Prepared by Dr. Heba Mohamed Lecturer of microbiology and immunology dpt. Aswan university Course outline Introduction to Stem cells : definition, types and potency. Stem cell niches and sources. Clinical application of stem cell therapy. Challenges in stem cell therapy. Ethical consideration and regulatory roles in stem cell therapy. Stem cells are the body's raw materials — cells from which all other cells with specialized functions are generated. stem cells are undifferentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. stem cells are blank cells that can give rise to multiple tissue types such as :skin ,muscle and nerve cell. Stem cells are essentially the building block of the human body. Properties of stem cell: They are unspecialized. They do not have any tissue-specific structures that allow for specialized function Self renewal :Capable of dividing and renewing themselves for long period Potency: they can give rise to all differentiated cell Plasticity: they are undifferentiated cells that can change into various types of cells They are uncommitted until they receive signal to develop into specialized cell  Stem cell classification based on : Source Potency Embryonic Adult Totipotent Pleuripotent Multipotent Unipotent Potency of stem cell is defined by the types of more differentiated cells that the stem cell can make. Totipotent : have the ability to differentiate into all types; can form any cell of the embryo as well as the placenta – Ex: morula Pluripotent: have the ability to differentiate into almost all types except placental tissue – Ex: cells from inner cell mass of blastocyst Multipotent : can differentiate into multiple specialized cells. can only make cells within a given germ layer. For example, multipotent stem cells from a mesodermal tissue like the blood can make all the cells of the blood, but cannot make cells of a different germ layer such as neural cells (ectoderm) or liver cells (endoderm). Unipotent : these cells only produce one cell type, but have the property of self renewal which distinguishes them from the non stem cells ,Ex: muscle stem cells, cardiac stem cells Embryonic stem cells (ES cells) They are derived from the inner cell mass of a blastocyst, an early stage pre implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (ICM) results in destruction of the blastocyst, which raises ethical issues Embryonic stem cell development They are pluripotent cells , they are able to differentiate into all derivatives of the three primary germ layers: ectoderm, endoderm, and mesoderm. These include each of the more than 220 cell types in the adult body. Pluripotency distinguishes embryonic stem cells from adult stem cells found in adults; while embryonic stem cells can generate all cell types in the body, adult stem cells are multipotent and can produce only a limited number of cell types. Adult stem cell  They are thought to be an undifferentiated cell, found among differentiated cells in a tissue or organ.  The adult stem cell can renew itself and can differentiate to yield some or all of the major specialized cell types of the tissue or organ.  The primary roles of adult stem cells in a living organism are to maintain and repair the tissue in which they are found  They function to : 1. Replace physiologically lost cells e.g. Blood (Hematopoietic stem cells). GIT epithelial cells Skin & Hair (epidermis, hair follicles, and sebaceous glands are replaced by stem cells). 2. Divide in response to tissue injury or infection e.g. Skeletal Muscle regeneration as a response to exercise or injury  Sources of stem cells  Excess embryos from assisted reproductive technologies such as commonly used in fertility clinics embryos created through in vitro fertilization  Other sources of stem cells are those from umbilical cord blood, and bone marrow. In addition, neural stem cells, haematopoetic stem cells and mesenchymal stem cells can be harvested from fetal blood and fetal tissue.  Umblical cord blood (also known as placental blood). It is the blood that flows in the circulation of the developing fetus in the womb. After the baby’s birth, the left over blood in the umbilical cord and placenta is called cord blood.  This blood is a rich source of stem cells as compared to adult stem cells. able to expand rapidly. Stored cord blood stem cells from a child is the perfect match for that child. This allows for an autologous transplant if needed, with no risk of Graft- vs- Host Disease(GVHD). Cord blood stem cells are a close match for siblings or family members in case of need, with low risk of GVHD. When to collect baby’s cord blood stem cells?  If there is a family history of malignant, benign or inherited disorders. In the presence of “health risk factors”, as there are potential benefits to family in the future. If the costs are affordable and this is something of value.  Collecting cord blood stem cells This blood is collected by the physician after the baby is born and the cord is cut. It takes less than 5 minutes and there is no pain, harm or risk to mother or newborn. This cord blood containing the stem cells, is sent to a “Cord Blood Bank” either private or public where it is processed and the stem cells are preserved in liquid nitrogen.  Immediately after the baby is delivered umbilical cord is clamped. After delivery of placenta , the placenta is placed on supporting frame , the cord is cleaned and needle is inserted into the umbilical vein.The umbilical cord blood is collected in a closed system and blood drained as a “standard gravity phlebotomy.” Collecting cord blood stem cells Second method involves collecting the cord blood while the placenta is still in the mother’s womb. This method has theoretically two advantages :collection begins earlier before the blood has a chance to clot. It uses the contraction of the uterus to enhance the blood drainage in addition to the gravity. Disadvantage: it is more intrusive and has the potential to interfere with after- delivery care for the mother and infant. The cord blood collected from single placenta is called a cord blood unit ranging from 60-120 ml. Advantages of embryonic Disadvantages of embryonic stem cell stem cell  Flexible - appear to have the  Difficult to differentiate potential to make any cell. uniformly and homogeneously into a target tissue.  Immortal - one embryonic  Immunogenic - embryonic stem cell line can potentially stem cells from a random provide an endless supply embryo donor are likely to be of cells with defined rejected after transplantation. characteristics.  Tumorigenic - capable of  Availability - embryos from forming tumors or promoting in vitro fertilization clinics.. tumor formation.  Destruction of developing human life. Advantages of adult stem Disadvantages of adult stem cell cell  Adult stem cells from bone  Limited quantity - can marrow and umbilical cords sometimes be difficult to appear to be as flexible as the embryonic type obtain in large numbers.  Not immunogenic - recipients  Finite - may not live as long who receive the products of as embryonic stem cells in their own stem cells will not culture. experience immune rejection.  Relative ease of procurement -  Less flexible - may be more some adult stem cells are easy difficult to reprogram to to harvest (skin, muscle, form other tissue types marrow, fat)  Non-tumorigenic-tend not to form tumors.  No harm done to the donor. Induced pluripotent stem cells (iPSCs)  Pluripotent stem cells hold promise in the field of regenrative medicin. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease iPSCs They are adult cells that have been genetically reprogrammed to an embryonic stem cell like state by being forced to express genes and factors important for maintaining the defining properties of embryonic stem cells. The iPSC technology was pioneered by Shinya Yamanaka in Kyoto ,Japan , who showed in 2006 that the introduction of four specific genes (named Myc, OCT3/4, Sox2 and KLF4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. Shinya Yamanaka was awarded the 2012 Nobel Prize for the discovery that mature cells can be reprogrammed to become pluripotent.  Applications 1- Can be used to study development Stem cells may help us understand how a complex organism develops from a fertilized egg. In the laboratory, scientists can follow stem cells as they divide and become increasingly specialized, making skin, bone, brain, and other cell types. Identifying the signals and mechanisms that determine whether a stem cell chooses to carry on replicating itself or differentiate into a specialized cell type, and into which cell type, will help us understand what controls normal development. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation. A better understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. This is an important goal of stem cell research. 2-Cell based therapies( Regenerative therapy)  The ability of stem cells to self-renew and give rise to different cells, that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.  This property is already used to restore the blood system in patients with leukaemia and other blood disorders. 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.  Stem cells may also hold the key to replacing cells lost in many other devastating diseases(experiments to graft new skin cells to treat serious burn victims, and to grow new corneas for the sight-impaired) for which there are currently no sustainable cures. In all of these uses, the goal is for the healthy cells to become integrated into the body and begin to function like the patient's own cells. Today, donated tissues and organs are often used to replace damaged tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, if they can be directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including: Parkinson's, heart disease, Alzheimer’s, spinal cord injury, stroke and diabetes. 3- can be used to study disease In many cases it is difficult to obtain the cells that are damaged in a disease, and to study them in detail. Stem cells, either carrying the disease gene or engineered to contain disease genes, offer a viable alternative. Scientists could use stem cells to model disease processes in the laboratory, and better understand what goes wrong 4- Stem cells could provide a resource for testing new medical treatments New medications could be tested for safety on specialized cells generated in large numbers from stem cell lines reducing the need for animal testing. Cancer cell lines, for example, are used to screen potential anti-tumour drugs. Obstacles to cell research Source :How to find the right type of stem cells? How to put the stem cells into the right place? Will the stem cells perform the desired function in the body?  Delivery to target areas Stem cell regenerated tissue viability Prevention of rejection Cell lines may have mutations. stem cell is unstable and mutate in culture like ordinary cells, stem cells accumulate significant numbers of mutations over time, including several that could cause them to become tumors Suppressing tumors Political and religious obstructions Inability to obtain source material due to ethical concerns