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Introduction to Stem Cells

• Stem cells are defined by their ability to regenerate into different cell types, possessing unique potencies.

• Ethical concerns regarding certain types of stem cells emerged prominently in the 1990s and early 2000s, especially pertaining to embryonic stem cells.

Types of Stem Cells

Potency Types of Stem Cells

• Totipotent Stem Cells:

  • Able to develop into all cell types including extra-embryonic tissues.

  • Example: Zygote (not a stem cell by definition as it does not divide).

• Pluripotent Stem Cells:

  • Can generate all types of cells except for extra-embryonic tissue.

  • Example: Embryonic stem cells (derived from the inner cell mass of the blastocyst).

  • Capable of self-renewal (dividing to form identical cells) and differentiation into various cell types.

• Multipotent Stem Cells:

  • Can differentiate into multiple cell types within a specific tissue.

  • Examples include stem cells found in skin, blood, and brain that can yield specific cell lineages but are restricted to their tissue of origin.

• Limited Progenitor Cells:

  • Have restricted differentiation abilities to form only one cell type.

Sources of Embryonic Stem Cells

• Isolated from the inner cell mass of blastocysts during early embryonic development.

• Initially cultured on feeder layers, primarily mouse fibroblasts, which provide necessary support for growth.

• Significant potential for expansion as these cells can proliferate indefinitely while maintaining pluripotency.

Maintenance of Pluripotency

• Pluripotent stem cells require active maintenance of their pluripotent state.

• Essential growth factors and transcription factors (e.g., Oct4, SOX2, Nanog) regulate gene expression and chromatin structure, ensuring cells remain undifferentiated.

• Positive feedback loops among transcription factors preserve their expression levels, while repressing differentiation-inducing factors.

• The balance of these factors dictates the differentiation pathways the cells can follow.

Testing Pluripotency

In Vivo Testing

• Injection of cultured embryonic stem cells into a blastocyst to assess their capacity for in vivo differentiation and contribution to tissue development, leading to chimeric mice formation.

• Confirmation of pluripotency through the ability to generate all somatic cell types upon differentiation in vivo.

In Vitro Applications

• Differentiation of embryonic stem cells into various cell types (e.g., neurons, pancreatic cells) to study disease mechanisms, drug testing, or tissue regeneration.

Applications and Ethical Considerations

Disease Modeling

• Human embryonic stem cells can be genetically modified to mirror specific patient mutations, enabling the study of disease mechanisms in vitro.

• Example: Studies involving fatty acid synthase mutations in neurons derived from embryonic stem cells to investigate potential treatments.

Potential Therapies

• Embryonic stem cells hold promise for regenerative medicine, including cell replacement for conditions like Parkinson's disease.

• Accelerated cell proliferation poses risks of tumor formation (teratomas), necessitating careful differentiation and engraftment strategies.

Induced Pluripotent Stem Cells (iPSCs)

• iPSCs are derived from fully differentiated somatic cells through the introduction of key transcription factors (e.g., Oct4, SOX2, Klf4, c-Myc).

• The reprogramming process takes time (weeks) and allows for the generation of pluripotent cells without ethical concerns related to embryonic cells.

• iPSCs can differentiate into various cell types, expanding options for modeling diseases, drug testing, and potential therapies.

Summary

• Stem cells possess incredible potential for both scientific research and therapeutic applications. While embryonic stem cells provide versatile options for differentiation, advances in iPSC technology offer ethical alternatives, paving the way for innovative treatments and disease understanding.