3.1 Types and sources of stem cells

Stem cells are the building blocks of life, capable of transforming into various cell types. They come in different flavors: embryonic, adult, and induced pluripotent. Each type has unique properties and potential uses in regenerative medicine.

Understanding stem cell types and sources is crucial for harnessing their power in treating diseases. From embryos to adult tissues, researchers are exploring diverse ways to obtain and manipulate these versatile cells, opening doors to groundbreaking therapies and scientific discoveries.

Stem cell classification

Stem cell types based on origin

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• Embryonic stem cells (ESCs) originate from the inner cell mass of a blastocyst
  • Pluripotent, capable of differentiating into all cell types of an organism except extraembryonic tissues
  • Derived from unused embryos donated from in vitro fertilization (IVF) procedures
  • High proliferative capacity and broad differentiation potential
  • Associated with ethical concerns and a higher risk of teratoma formation
• Adult stem cells (ASCs) are found in various tissues throughout the body
  • Multipotent, capable of differentiating into multiple cell types within a specific lineage
  • Can be isolated from tissues such as bone marrow, adipose tissue, dental pulp, and umbilical cord blood
  • More limited differentiation potential compared to ESCs
  • Less ethically controversial and lower risk of immune rejection in autologous transplantation
• Induced pluripotent stem cells (iPSCs) are created by reprogramming adult somatic cells to a pluripotent state
  • Reprogramming achieved using specific transcription factors (Oct4, Sox2, Klf4, and c-Myc)
  • Exhibit properties similar to ESCs, including pluripotency and high proliferative capacity
  • Can be derived from a patient's own cells (skin fibroblasts or blood cells), reducing immune rejection risk
  • Reprogramming process may introduce genetic and epigenetic abnormalities

Stem cell potency hierarchy

• Totipotent stem cells can form an entire organism, including extraembryonic tissues (placenta and yolk sac)
  • Example: Zygote and early blastomeres (up to the 4-cell stage)
• Pluripotent stem cells can differentiate into all cell types of an organism, except extraembryonic tissues
  • Examples: Embryonic stem cells and induced pluripotent stem cells
• Multipotent stem cells can differentiate into multiple cell types within a specific lineage
  • Examples: Hematopoietic stem cells (can form all blood cell types) and mesenchymal stem cells (can form bone, cartilage, and fat cells)
• Oligopotent stem cells can differentiate into a few cell types within a specific lineage
  • Example: Lymphoid progenitor cells (can form B and T lymphocytes)
• Unipotent stem cells can differentiate into only one cell type
  • Example: Spermatogonial stem cells (can form sperm cells)

Stem cell sources

Embryonic and perinatal sources

• Embryonic stem cells are derived from the inner cell mass of a blastocyst
  • Typically obtained from unused embryos donated from in vitro fertilization (IVF) procedures
  • Requires the destruction of the embryo, raising ethical concerns
• Perinatal stem cells can be obtained from extraembryonic tissues
  • Sources include the placenta, amniotic fluid, and umbilical cord tissue (Wharton's jelly)
  • Less ethically controversial compared to embryonic stem cells
  • Have a lower risk of immune rejection in allogeneic transplantation

Adult tissue sources

• Adult stem cells can be isolated from various tissues throughout the body
  • Bone marrow contains hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs)
  • Adipose tissue (fat) is a rich source of mesenchymal stem cells
  • Dental pulp from extracted teeth contains dental pulp stem cells (DPSCs)
  • Umbilical cord blood is a source of hematopoietic stem cells and mesenchymal stem cells
• Isolation methods include tissue digestion, centrifugation, and cell sorting techniques (FACS or MACS)
• Adult stem cells are less abundant in tissues compared to embryonic sources
• Autologous transplantation using adult stem cells reduces the risk of immune rejection

Induced pluripotent stem cell generation

• Induced pluripotent stem cells are created by reprogramming adult somatic cells
  • Reprogramming achieved using a combination of transcription factors (Oct4, Sox2, Klf4, and c-Myc)
  • Somatic cell sources include skin fibroblasts, blood cells, and urine-derived cells
• Reprogramming methods include viral vector delivery, mRNA transfection, and small molecule compounds
• iPSCs can be derived from a patient's own cells, enabling personalized regenerative therapies
• Reprogramming efficiency is relatively low, and the process may introduce genetic and epigenetic abnormalities

Stem cell properties

Self-renewal and proliferation

• Stem cells can self-renew, maintaining their undifferentiated state through numerous cell divisions
  • Symmetric division: One stem cell divides into two identical daughter stem cells
  • Asymmetric division: One stem cell divides into one identical daughter stem cell and one differentiated cell
• High proliferative capacity allows stem cells to generate large numbers of cells for regenerative applications
  • Embryonic stem cells have the highest proliferative capacity, followed by induced pluripotent stem cells
  • Adult stem cells have a more limited proliferative capacity compared to ESCs and iPSCs

Differentiation potential

• Stem cells can differentiate into specialized cell types under appropriate conditions
  • Differentiation is triggered by specific signaling molecules, growth factors, and extracellular matrix components
  • Embryonic stem cells and induced pluripotent stem cells have the broadest differentiation potential (pluripotent)
  • Adult stem cells have a more limited differentiation potential (multipotent or unipotent)
• Directed differentiation protocols guide stem cells towards specific cell lineages
  • Examples: Neuronal differentiation, cardiomyocyte differentiation, and hepatocyte differentiation
• Differentiated cells can be used for disease modeling, drug screening, and cell replacement therapies

Homing and engraftment

• Stem cells can home to sites of injury or inflammation in the body
  • Homing is mediated by chemokines, cytokines, and adhesion molecules
  • Examples: SDF-1/CXCR4 axis in hematopoietic stem cell homing to bone marrow
• Engraftment refers to the ability of transplanted stem cells to integrate and survive in the target tissue
  • Requires appropriate cell-cell and cell-matrix interactions
  • Immunological compatibility between the donor and recipient is crucial for successful engraftment
• Strategies to enhance homing and engraftment include tissue engineering and co-transplantation with supporting cells

Ethical considerations for stem cells

Embryo destruction and moral status

• The use of embryonic stem cells is ethically controversial due to the destruction of human embryos
  • Raises concerns about the moral status of the embryo and the beginning of human life
  • Some view the embryo as a potential human being with the right to life
  • Others consider the embryo as a collection of cells without moral status until later developmental stages
• Alternative sources of pluripotent stem cells, such as induced pluripotent stem cells, circumvent this ethical issue
  • iPSCs are derived from adult somatic cells, avoiding the need for embryo destruction
  • However, the use of iPSCs may still raise concerns about the potential for misuse, such as creating genetically modified human embryos

Informed consent and commercialization

• Informed consent is essential for the donation of stem cells or somatic cells for reprogramming
  • Donors must be fully informed about the purpose of the research, potential risks, and the use of their cells
  • Consent processes must ensure voluntariness and protect donor privacy and confidentiality
• Commercialization of stem cell therapies raises ethical concerns
  • Equitable access to stem cell treatments, regardless of socioeconomic status
  • Potential exploitation of vulnerable populations, such as women in developing countries, for stem cell tourism
  • Ensuring the safety and efficacy of stem cell products through rigorous clinical trials and regulatory oversight

Chimera formation and species boundaries

• The creation of human-animal chimeras for research purposes raises ethical concerns
  • Chimeras are organisms containing cells from two or more individuals or species
  • Examples: Human stem cells injected into animal embryos to study human development and disease
  • Blurring of species boundaries and the potential for human cells to contribute to animal gametes or brains
• Ethical guidelines and regulations are needed to ensure responsible chimera research
  • Limiting the contribution of human cells to specific tissues or developmental stages
  • Prohibiting the breeding of chimeric animals to prevent the transmission of human traits
  • Ongoing dialogue between scientists, ethicists, and policymakers to address emerging ethical challenges