Haematopoietic Stem Cell Sciences PDF

Chapter 1 Introduction to Haematopoietic Stem Cells Medical Laboratory Sciences Haematopoietic Stem Cell Sciences Dr. Ali Abdelfattah  Headlines Embryogenesis Definition of stem cells Properties of stem cells Different types...

Chapter 1 Introduction to Haematopoietic Stem Cells Medical Laboratory Sciences Haematopoietic Stem Cell Sciences Dr. Ali Abdelfattah  Headlines Embryogenesis Definition of stem cells Properties of stem cells Different types of stem cells Applications of stem cells Challenges of stem cell research  Embryogenesis Embryology is the study of embryos and their development. Embryonic period vs Fetal period ▪ Embryonic period is first 8 weeks after fertilization including the development of the three primary germ layers that give rise to all body structures. ▪ Fetal period is a period of 30 weeks, where organs continue to grow and develop. ❑Human body composed of approximately 220 types of cells with about 50-75 trillion cells.  Embryogenesis Stages of development Fertilization: The process of fusion of the sperm with the mature ovum, producing the fertilized single mono- nucleated cell called the zygote. Cleavage: a sequence of rapid mitotic divisions (without cell growth). Cleavage starts approximately 30 hrs after fertilization. Gastrulation: A phase in which the single-layered structure (blastula) converts into a three-layered structure known as the gastrula.These three germ layers are known as the ectoderm, mesoderm, and endoderm. Organogenesis: The production and development of the organs  Embryogenesis Cleavage The morula enters the (Day 3-4) uterus approximately 4 days after fertilization. Fluid accumulates within the morula and forms blastocyst 6-7 days after Fallopian tube fertilization, the blastocyst attaches to the endometrium and (Day 5-6) implantation begins Implantation Three germ layers forms around 2 weeks after fertilization).  Embryogenesis ▪ Trophoblast: layer of outer cells that will form the placenta ▪ Blastocoel: inside the blastocyst that will form body cavity ▪ Inner cell mass (Embryoblast, ESCs): inside the blastocyst that will form the embryo Upon implantation of the blastocyst, the trophoblast will differentiate into the cytotrophoblast and the syncytiotrophoblast. ▪ The syncytiotrophoblast produces human chorionic gonadotropin (hCG). Secreted hCG enters the maternal blood circulation and is approximately sufficient by the end of the second week post fertilization to yield a positive pregnancy test. Embryogenesis The embryoblast undergoes cellular differentiation into two layers: the hypoblast, which forms the yolk sac, and the epiblast, which forms the amnion. These two layers will give rise to the three germ cell layers that will form all the body’s tissues and organs. Ectoderm generates the outer layer of the embryo and produces the skin cells and the nervous system Endoderm becomes the innermost layer of the embryo and gives rise to the cells that line the internal organs including gut, liver, lungs, and pancreas Mesoderm becomes the middle layer between the ectoderm and endoderm and generates the blood, heart, kidney, bones, and connective tissues  What Are Stem Cells? Stem cells provide the starting material for every organ and tissues Difference between stem cell and other body cells ▪ Ability to divide throughout life ▪ Ability to differentiate into many different cell types ❑ Stem cells are the mother cells that have the ability to continuously reproduce themselves and differentiate into other kinds of cells/tissues (specialized cells) The unique properties of all stem cells  Unique properties of stem cells Stem cells are unspecialized cells They do not yet have any tissue specific structures that allow them to perform specialized function. Self-renewal potential They can undergo unlimited cell division to repopulate themselves for indefinite periods Differentiation (Potency) Stem cells can differentiate under proper physiological conditions to specialized cells such as heart muscle cells, blood cells or nerve cells required to repair damaged or depleted cells Plasticity Stem cell from one tissue may be able to give rise to cell types of completely different tissue e.g. Haematopoietic stem cells becoming nerve cells or heart cells Stem cell potency  Stem cell potency ❑ Totipotent stem cells: can become any cell in body, placenta, and umbilical cord Each cell can form a complete organism ❑ Pluripotent stem cells: can become any cell in body Undifferentiated inner cell mass of blastocyst Form approximately 200 different cell types ❑ Multipotent stem cells: can become any cell within a specific tissue/organ Ability to differentiate is more limited  Stem cell potency The difference between totipotent and pluripotent cells depends on the cellular potency The difference between totipotent and pluripotent cells is only that totipotent cells can give rise to the placenta, the umbilical cord, and the embryo, while pluripotent cells can only give rise to the embryo Totipotent stem cells form around 220 different cell types Pluripotent stem cells form around 200 different cell types Stem cell potency Stem cell timeline Stem cells exist in both embryos and adults  Types of stem cell ❑Pluripotent stem cells Embryonic stem cells (ESCs) Induced pluripotent stem cells (iPSCs) ❑Multipotent stem cells Cord blood stem cells Placenta stem cells Tissue-specific stem cells (Adult stem cells) Hematopoietic stem cells (HSCs) Mesenchymal stem cells (MSCs) Intestinal stem cells Endothelial stem cells Neural stem cells  Pluripotent stem cells Pluripotency describes the ability of a cell to develop into the three primary germ cell layers of the early embryo and therefore into all cells of the adult body Embryonic stem cells (ESCs) Induced pluripotent stem cells (iPSCs)  Embryonic stem cells (ESCs) Embryonic stem cells (ESCs) are derived from inner cell mass of the blastocyst, a ball of around 50 cells, which develops 5-6 days after conception, before the embryo implants in the uterus ESCs are pluripotent stem cells ▪ These cells have self-renew potential ▪ These cells can differentiate to become almost every cell in the body  Embryonic stem cells (ESCs) Researchers extract ESCs from a 5-6 days old blastocyst ESCs can divide in culture to form a new stem cell line. The research aims to induce these cells to generate healthy tissue needed by patients.  Induced pluripotent stem cells (iPSCs) ❑ Scientists have recently discovered how to turn adult stem cells (multipotent stem cells ) into pluripotent stem cells. These cells are called induced pluripotent stem cells (iPSCs). They can differentiate into all types of specialized cells in the body. This means they can potentially produce new cells for any organ or tissue. iPSCs are generated by process known as “de-differentiate” It is a process by which cells develop in reverse and become less specialized, from a more differentiated to a less differentiated state. To create iPSCs, scientists genetically reprogram the adult stem cells so they behave like embryonic stem cells.  Induced pluripotent stem cells (iPSCs) ❑ Scientists are hoping that the cells can be made from someone’s own skin to treat a disease. This will help prevent the immune system from rejecting an organ transplant. Research is underway to find ways to produce iPSCs safely  Multipotent stem cells ❑ Multipotent stem cells can develop into more than one cell type, but are more limited than pluripotent cells ❑ Multipotent stem cells have the capacity to self-renew and to develop into multiple specialised cell types present in a specific tissue or organ ❑ Types of Multipotent stem cells Cord blood stem cells Placenta stem cells Tissue-specific stem cells (Adult stem cells) Hematopoietic stem cells (HSCs) Mesenchymal stem cells (MSCs) Intestinal stem cells Endothelial stem cells Neural stem cells  Cord blood stem cells Cord blood stem cells are harvested from the umbilical cord after childbirth. These cells can be frozen in cell banks for use in the future Cord blood stem cell transplants are less prone to rejection than either bone marrow or peripheral blood stem cells. This is probably because the cells have not yet developed the features that can be recognized and attacked by the recipient's These cells have been successfully used immune system to treat and cure chronic blood-related disorders such as Sickle cell disease, Thalassemia, and Leukaemia  Placenta stem cells Placenta is a good source of multipotent stem cells Placental stem cells, like umbilical cord blood, can be used to cure chronic blood- related disorders such as sickle cell disease, Thalassemia, and Leukaemia. The placenta is comprised of many stem cells that are also found within cord tissue. However, cord blood stem cells are a pure source of fetal stem cells, whereas the placenta is a mix of stem cells, some of which are maternal. Therefore, stem cells from the placenta can be contaminated with trace amounts of maternal cells, not easily isolated from fetal cells.  Adult stem cells (Tissue specific stem cells) Adult stem cells have a misleading name, because they are also found in infants and children. These stem cells come from developed organs and tissues in the body. In contrast to the ESCs, which are pluripotent, adult stem cells have a more restricted differentiation capacity and are usually lineage specific. Adult stem cells act as a repair system for the body, replacing damaged tissue in the same area in which they are found, such as blood, skin or intestinal tissues. Embryonic vs Adult Stem Cells Embryonic stem cells Adult stem cells Pluripotent stem cells, Multipotent stem cells Differentiate into any cell types Differentiate into some cell types Known Source Unknown source Large numbers can be harvested Limited numbers, more difficult from embryos to isolate May cause immune rejection Less likely to cause immune rejection, since the patient’s own cells can be used Ethical issues - when does life No ethical issues begin?  Adult stem cells (Tissue specific stem cells) Hematopoietic stem cells (HSCs) Mesenchymal stem cells (MSCs) Intestinal stem cells Endothelial stem cells Neural stem cells  Haematopoietic stem cells Haematopoietic stem cells (HSCs) are multipotent stem cells and have both the self-renewal potential (HSCs replication and maintenance) to sustain HSCs pool size and the differentiation potential (formation of functional blood cells) to sustain mature blood cells homeostasis HSCs are anatomically localised in a specialised microenvironment that provides soluble factors that are essential for HSC regulation. This unique microenvironment is called the HSC niches  Haematopoietic stem cells The term haematopoiesis describes the formation of all types of blood cells from a small pool of HSCs  Mesenchymal stem cells (MSCs) MSCs are multipotent stem cells and make the different specialized cells found in the skeletal tissues.  Applications of stem cells Numerous diseases and damaged organs could potentially be treated with cell therapy. Stem cells can be used to generate healthy and functioning specialized cells, which can then replace diseased or dysfunctional cells. It is similar to the process of organ transplantation only the treatment consists of transplanting cells instead of organs ▪ Stem cell transplantation (SCT) is 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 malignant diseases in order to restore the normal blood cell production, such as leukaemia, lymphoma or myeloma  Applications of stem cells Cell therapy is also being used in experiments to graft new skin cells to treat serious burn victims, grow new corneas for the sight-impaired, and stems cells might be trained to become pancreatic islets cells needed to secrete insulin to treat patients with type I diabetes. Stem cells could allow scientists to test new drugs using human cell line which could speed up new drug development. It would allow quicker and safer development of new drugs. ❖ 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.  Challenges of stem cell research Is stem cell research ethical? Embryonic stem cells - Morally objectionable Harvesting ESCs destroy the blastocyst. This is murder when does life begin? o If the embryo is inanimate matter, then the resistance to embryonic stem cell research is unreasonable. o If the embryo is alive matter, then embryonic stem cell research is immoral. ✓ ESCs are unstable and mutate in culture. They accumulate significant numbers of mutations over time and may become tumours Umbilical cord stem cells - Morally acceptable The umbilical cord is no longer required once the delivery has been completed. Adult stem cells - morally acceptable