From the authors
Preface
Introduction
List of abbreviations used
A timeline of the major research that led to the discovery of stem cells
- Detecting the replicative senescence threshold of cells
- Discovery of the clonal expansion capacity of stem cells
- Discovery of the pluripotency property of stem cells
- Development of stem cell research in recent years
Stem Cell Biology
- Basic characteristics of stem cells
- Self-updating
- Cellular niche
- Peculiarities of the cell cycle in stem cells
- Telomeres and telomerase
- Asymmetric division in stem cells
- Asymmetric segregation of DNA between daughter cells
- Stem cell potency
- Molecular mechanisms of pluripotency and signaling pathways involved in maintaining the undifferentiated state of the cell
- Epigenetic regulation of chromatin structure in stem cells
- Non-coding RNAs and pluripotency
- Peculiarities of stem cell metabolism
- Commitment (commitment) of stem cells to a certain path of differentiation
- Ability to incorporate different cellular context
Molecular markers characterizing the undifferentiated state of cells
- Oct4
- Sox2
- Nanog
- Other markers typical of the undifferentiated state
Types of stem cells
- Embryonic stem cells
- Embryonic germ stem cells
- Amniotic stem cells
- Cord blood stem cells
- Placental stem cells
- Adult stem cells
- Induced pluripotent stem cells
- "Naïve" and "primed" stem cells
- It turns out that pluripotent cells aren't actually 'tabula rasa'
- Major differences between the 'naïve' and 'primed' states of pluripotent cells
- Peculiarities of the transition between the "naive" and the "prepared" state
- Cancer stem cells
- Concept of "cancer stem cell"
- Key components of cancer stem cell signaling pathways
- Induction of differentiation in cancer cells. Induction therapy
Cell differentiation and dedifferentiation
- Undifferentiated and differentiated state of the cell
- Factors controlling the process of cell differentiation
- Extracellular factors
- Intracellular factors
- DNA methylation
- Cell renewal in the adult organism
- Differentiation of epidermal cells (including squamous epithelium)
- Differentiation of blood cells
- Differentiation of muscle cells
- nerve cell differentiation
- Differentiation of non-epidermal epithelial cells
- Differentiation of cells of parenchymal organs
- Dedifferentiation and transdifferentiation
Stem cell banking. Legal, ethical and religious aspects
- Basic definitions
- Types of stem cell banks
- Types of stem cell banks according to the type of cells they receive, process and store
- Types of stem cell banks according to the order of use of the cells and the source of funding of their activities
- Normative regulation of scientific research activity on stem cells and their use
- The situation in Bulgaria regarding the legal framework for research on stem cells and their use
- Umbilical cord blood stem cell banking
- Banking "adult" stem cells
- Embryonic stem cell banking
- An overview of the views of the world's major religions on the status of embryos and fetuses as human beings
- Key parameters of stem cell banking worldwide
Immunological individuality and immune rejection
- Historical Review - Charge and Development of Transplantation Science
- Blood transfusion attempts
- Attempts at organ transplantation
- Structure and functions of the major histocompatibility complex (MHC)
- overview
- Genetics of the MHC cluster
- Nomenclature of HLA types
- Practical basics of HLA typing
- Mechanisms of immune rejection
- Types of rejection
- Mechanisms of recognizing "own" from "other"
- Peculiarities of rejection of transplanted tissues and organs
- Immunologically privileged transplants
- Strategies to overcome immune rejection of transplanted tissues, organs and cells
- Compatibility between donor and recipient
- Banks and databases of different types of stem cells with potential application for transplantation purposes
Immunological and other aspects of stem cell therapeutic applications
- Dose effect in cord blood stem cell transplantation
- Some more common side effects in cell and tissue donors and recipients
- Adverse reactions in donors
- Adverse reactions in recipients
- Graft-versus-host disease (GVHD)
- Adverse posttransplantation reactions associated with immune compromise in the recipient
- Tumorigenic properties of pluripotent stem cells
- Immunosuppressive therapy for the treatment of various human diseases and conditions
- Some more common human diseases and conditions associated with carriage of specific HLA types
- Peculiarities of the ratio of the frequency of autoimmune diseases in both sexes
Principles of work organization in stem cell banks
- Spatial and architectural organization of stem cell banks
- Standards for handling stem cells and cell products
- General requirements of good manufacturing practice
- Specific requirements of good manufacturing practice
- Documentation
- Production
- Quality control
- Other special requirements for the manufacture of medicinal preparations for therapy based on cell products
Traceability in stem cell banks
- Definitions
- Identification of the identity of the donor
- Who has the right to give consent for cell and tissue donation?
- Obtaining consent for cord blood collection
- Obtaining consent to use human embryos for scientific research purposes
- Obtaining consent to donate adult stem cells
- Donor selection criteria
- Laboratory studies of donors
- Data required and held by organizations involved in the collection, banking and use of human cells and tissues
- Traceability of samples and confidentiality of personal information
- Traceability in action: finding a suitable donor
- Selection of compatible donors
- In search of an HLA-match: how many units should be in a bank to have a chance of finding a compatible donor
Applied aspects of the knowledge of cell differentiation and transdifferentiation for the purposes of regenerative medicine
- How to make stem cells produce the specific cell type needed
- Dedifferentiation and transdifferentiation of stem cells for the treatment of human disease
- Reduction of tumorigenic potential of pluripotent stem cells
- Vectors for the transfer of genomic fragments into stem and differentiated cells
Current state of science and medicine regarding application of stem cell therapy
- Treatment with one's own stem cells - insurance for the future or rich ground for speculation
- Treatment of hereditary diseases with own stem cells
- Cancer treatment with own stem cells
- State of science and medicine regarding treatment of specific diseases and conditions
- Scientific fraud and unprofessional conduct in transplant science and stem cell research
- Difference between unprofessional conduct in science and scientific fraud
- "The chess mouse" - the simplest example of scientific fraud
- Fabricating experimental data is also a simple and effective method of committing scientific fraud
- Potential influence of big pharmaceutical companies
- Misrepresentation of experimental results due to random or systematic errors
- Cell therapy that kills
- Bad faith and/or incorrect use of the possibilities of cell therapy
Glossary of terms
Abstract (in Bulgarian)
Abstract (in English)