Lecture - Stem Cells: Difference between revisions

Revision as of 17:56, 10 October 2011

Introduction

Week 1 human development

Embryology is all about stem cells, a single cell (zygote) divides and differentiates to form all the tissues throughout the body. Furthermore within some tissues, stem cells remain to continuously replace cells that are lost through the life of that tissue. In recent years Scientific and general interest in this topic has increased due to the many issues that surround this specialised cell type. This lecture will introduce the various types/sources of stem cells as well as their practical and therapeutic potentials. A brief discussion of the pros and cons of different types of stem cells currently investigated in the field of medical research will be discussed.

Textbooks

Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8^th ed.). Philadelphia: Saunders.

(chapter links only work with a UNSW connection).

Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4^th ed.). New York; Edinburgh: Churchill Livingstone.

(chapter links only work with a UNSW connection).

Hill, M.A. (2011) UNSW Embryology (11^th ed.). Sydney:UNSW.

Links: Embryology Textbooks | NIH - Regenerative Medicine 2006

Embryonic vs Adult Stem Cells

Embryonic Stem Cell Advantages

Pluripotency - ability to differentiateinto any cell type.
Immortal - one cell can supply endless amounts of cells.
Easily available - human embryos from fertility clinics.

Embryonic Stem Cell Disadvantages

Unstable - difficult to control differentiation into specific cell type.
Immunogenic - potential immune rejection when transplanted into patients.
Teratomas - tumor composed of tissues from 3 embryonic germ layers.
Ethical Controversy - unethical for those who believes that life begins at conception.

Adult Stem Cell Advantages

Already ‘specialised’ - induction of differentiation into specific cell types will be easier.
Plasticity - Recent evidences suggest wider than previously thought ranges of tissue types can be derived.
No Immune-rejection - if used in autologous transplantations.
No Teratomas - unlike ES cells.
No Ethical Controversy - sourced from adult tissues.

Adult Stem Cell Disadvantages

Minimal quantity - number of isolatable cells may be small.
Finite life-span - may have limited lifespan in culture.
Ageing - stem cells from aged individuals may have higher chance of genetic damage due to ageing.
Immunogenic - potential immune rejection if donor cells are derived from another individual.

Inducible Stem Cell

embryonic stem cell signalling regulation

Human iPS cell clones^[1]

Yamanaka Factors

A set of 4 transcription factors when introduced into cells induces stem cell formation.^[2] These four transcription factors can be expressed from doxycycline (dox)-inducible lentiviral vectors. The only culture difference in iPS cells and human embryonic stem cell culture is that iPS cell culture require 100ng/ml of bFGF in the culture media.

Outline of the MEF reprogramming protocol 1 Outline of the MEF reprogramming protocol 2 | stained with anti-Rex1, Sox2 and SSEA1 antibodies

OCT4 Transcription factors containing the POU homeodomain
MYC The MYC protooncogene encodes a DNA-binding factor that can activate and repress transcription. Ectopic expression of c-Myc can also cause tumorigenicity in offspring.
SOX2 SRY-RELATED HMG-BOX GENE 2
KLF4 Kruppel-like factor 4, zinc finger protein, transcription factor which acts as both an activator and repressor.

More recently shown that Oct4 together with either Klf4 or c-Myc is sufficient to generate iPS cells from neural stem cells.^[3]

Thompson Factor