Regenerative Medicine PDF

Pharmaceutical Biotechnology Regenerative Medicine Dr. Esra’a Alomari 2022/2023 Course Number: 05027125 Dr. Esra'a Alomari Regenerative medicine Regenerative medicine is the branch of medicine that develops methods to regrow, repair or repla...

Pharmaceutical Biotechnology Regenerative Medicine Dr. Esra’a Alomari 2022/2023 Course Number: 05027125 Dr. Esra'a Alomari Regenerative medicine Regenerative medicine is the branch of medicine that develops methods to regrow, repair or replace damaged or diseased cells, organs or tissues. Regenerative medicine therapy, including cell therapy, gene therapy, and therapeutic tissue engineering, provides unprecedent potential to treat, modify, reverse, or cure previously intractable diseases, such as cancer and organ failures. Regeneration in humans happens at three levels: Molecular: This includes small molecules that are the building blocks of your body, like DNA, fats, and carbohydrates. Cellular: This includes cell structures like neurons or axons that are responsible for cell growth and reproduction in your body. Tissue: This includes blood, skin, bone, or muscle. Fully differentiated cells or groups of cells (organs and tissues) are currently in routine medical use. Such products include cells or tissues used for the purposes of transplantation, as well as a small number of engineered cell-based products. Dr. Esra'a Alomari Transplantation Transplantation entails the transfer of living cells/tissue/organs from a donor to a recipient. Autologous transplantation: In some cases (e.g. many skin grafting procedures) the donor and recipient are actually the same individuals. Allogeneic transplantation: the donor and recipient are different individuals. Common forms of transplantation include: whole blood transfusions. bone marrow transplantations. skin grafting. transplantation of a wide range of organs, including kidneys, liver, pancreas, lungs and heart. v Tissue/organs destined for transplant are rarely considered to be pharmaceutical products. Dr. Esra'a Alomari v Tissue- or cell-engineered’ products represent a small but significant subgroup of cell-based products. Such products also consist of/contain fully differentiated cells but do undergo some modification or formulation in vitro prior to their medical use. Examples include: Carticel: Apligraf: a skin substitute used in the treatment of certain ulcers, which is composed of keratinocytes and fibroblasts derived from human neonatal foreskin tissue and bovine collagen. Dr. Esra'a Alomari Stem cells Stem cells are usually defined as undifferentiated cells capable of self-renewal that can differentiate into more than one specialized cell type. Stem cells have two key properties: 1. The ability to self-renew, dividing in a way that makes copies of themself. 2. The ability to differentiate, giving rise to the mature types of cells that make up organs and tissues. Dr. Esra'a Alomari  Stem cells Stem cell therapy is a form of regenerative medicine designed to repair damaged cells within the body by reducing inflammation and modulating the immune system. Stem cell therapies have been used to treat autoimmune, inflammatory, neurological, orthopedic conditions and traumatic injuries with studies conducted on use for Crohn's disease, Multiple Sclerosis, Lupus, COPD, Parkinson's, ALS, Stroke recovery and more. Such cells are classified on the basis of their original source as either embryonic or adult stem cells. Dr. Esra'a Alomari Embryonic stem cells Embryonic stem cells have been derived from a variety of species including humans. They described pluripotent, as they can generate all different types of cells in the body. Embryonic stem cells are derived from pre-implant-stage human embryos, usually at the blastocyst stage. The blastocyst is a thin-walled hollow structure containing a cluster of cells, known as the inner cell mass, from which the embryo arises. Dr. Esra'a Alomari Embryonic stem cells Human embryonic stem cells are derived from blastocytes that were created by IVF. Treatment of blastocysts with pronase (a cocktail of proteolytic enzymes), to degrade the outer protective membrane known as the ‘zona pellucida’. The blastocysts are next treated with anti-human whole serum antibody and guinea pig complement, which triggers complement-mediated lysis of the blastocyst outer cell layers (the trophoblast), allowing recovery of The culture vessels often contain a layer of ‘feeder’ the inner cell mass. cells (e.g. mouse fibroblasts), irradiated in order to prevent their growth and division. The latter cells are then cultured under defined conditions in order to allow them to multiply while remaining undifferentiated. Dr. Esra'a Alomari Embryonic stem cells Feeder layer function: a) to provide a suitable substratum with which embryonic stem cells can interact, aiding in their growth and division. b) feeder cells can release often ill-defined nutrients into the medium, which can again support stem cell growth. v The presence of a feeder cell layer would represent a complication in the downstream processing of stem cells for therapeutic use and could represent a potential source of pathogenic contaminants. Ø The feeder layer is replaced by: Fibronectin: a glycoprotein found on the cell surface. Matrigel: a protein-rich membrane extract from a mouse sarcoma cell line). Dr. Esra'a Alomari Embryonic stem cells Research is going to identify an optimal cell culture medium composition that will facilitate strong cell growth while remaining in an undifferentiated state. Basic animal cell culture media are often supplemented with serum as a nutrient source. It is known that the addition of the cytokine LIF (Leukemia inhibitory factor) can sustain mouse embryonic stem cells in the undifferentiated state, but LIF alone cannot achieve this in the context of human embryonic stem cells. The application of such cells in regenerative medicine requires the subsequent controlled differentiation of such cells to generate a specific desired cell type. (e.g. a specific neuron type to treat a specific neurodegenerative disease). The process by which any stem cell differentiates naturally to form a specific cell is hugely complex and understood only in outline and only for a few cell types. Differentiation is dependent upon several concerted signals from effector molecules such as cytokines. A major challenge is to gain a more complete understanding of how differentiation into specific cell types is driven and controlled. Only with such knowledge will come the ability to grow specific cells (and ultimately tissue/organ types) from stem cells for the purposes of regenerative medicine. Dr. Esra'a Alomari  Dopaminergic-like neurons represents a significant milestone in the attempt to apply regenerative medicine to the treatment of Parkinson’s disease. Cell types have been achieved in one or more of three ways: 1. manipulation of culture media composition. 2. alteration of the surface characteristics of the matrix on which the cells are grown (e.g. adhesive feeder cells or specific protein-based matrices). 3. the introduction of specific regulatory genes into the stem cells themselves. Dr. Esra'a Alomari Adult stem cells Somatic stem cells, commonly referred to as adult stem cells (ASCs) or tissue-specific stem cells, are present throughout various tissues in the body. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. (The main physiological role appears to be to maintain and to repair) These cells can renew themselves and can differentiate to yield the major cell types characteristic of the tissue in which they reside. There are typically a small number of stem cells in each tissue. Due to their small number and rate of division (growth), it is difficult to grow adult stem cells in large numbers. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting. Dr. Esra'a Alomari Adult stem cells Dr. Esra'a Alomari Induced pluripotent stem cells Dr. Esra'a Alomari  Stem cells can be administered: § IV Stem Cell Therapy § Intrathecal (directly into the spinal canal) § Site injections into problem areas (Knee, hips, hands). The method of administration can have different effects on a patient and should be thoroughly considered prior to select a route. Dr. Esra'a Alomari Disease-or patient-specific pluripotent stem cells One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patient-specific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur. Dr. Esra'a Alomari