Stem Cells and the Maintenance of Adult Tissues

Chapt 17 2. Stem cells have great potential

Adult stem cells

Embryonic stem cells

In early development, cells proliferate rapidly, then differentiate to form specialized cells of adult tissues

Most differentiated cells in adult animals are no longer capable of proliferation.

If cells are lost, replace by proliferation of cells derived from self-renewing stem cells.

Stem Cells,Maintenance of Adult Tissues

1. Some differentiated cells can proliferate to repair damaged tissues Fibroblasts in connective tissue proliferate in response to platelet-derived growth factor (PDGF) released at wound

Endothelial cells lining blood vessels proliferate to form new blood vessels (repair and regrowth of damaged tissue) Triggered by vascular endothelial growth factor (VEGF), from cells that lack oxygen

Fig. 17.13,14, 15

Stem Cells and the Maintenance of Adult Tissues

2. Adult Stem cells:

Less differentiated, self-renewing cells in most adult tissues.

Retain capacity to proliferate, replace differentiated cells throughout lifetime of animal.

** Divide to produce one daughter cell that remains stem cell and one that divides, differentiates

Ex. blood cells, sperm, epithelial cells skin, intestine

Fig. 17.17

Fig 17.18 Formation of blood cells

Hematopoietic (blood-forming) stem cells were the first identified (1961): • distinct types • specialized functions• Short life span• from bone marrow

Stem Cells and Maintenance of Adult Tissues

Epithelial cells that line intestines live only a few days before they die

Fig. 17.19

Stem Cells and the Maintenance of Adult Tissues

Adult stem cells potential utility in medicine.

Hematopoietic stem cell transplantation (or bone marrow transplantation) important role in treatment of cancers.

Cord blood is source of hematopoietic stem cellsEpithelial stem cells - skin grafts for burns, wounds, and ulcers.

Fig. 17.22

Embryonic Stem Cells and Therapeutic Cloning

3. Embryonic stem cells (ES)

Grow indefinitely as pure stem cell populations Pluripotency — capacity to develop into all of

different types of cells in adult tissues.

Enormous interest - basic science and clinical applications.

Distinction cloning cells versus cloning organisms

Embryonic Stem Cells and Therapeutic Cloning

ES cells first cultured from mouse embryos in 1981.Mouse ES cells important experimental tool: Can introduce altered genes into mice. Model system to study molecular basis of cell differentiation

Fig. 17.23 ES cells can differentiate: Martin Expt: neuron-like, endodermal, cartilage

Embryonic Stem Cells and Therapeutic Cloning

Mouse ES cells need growth factor LIF, to maintain undifferentiated state (leukemia inhibitory factor)

LIF signals through JAK/STAT path If LIF is removed, cells aggregate and differentiate. Different growth factors direct differentiation along specific paths

Model for future human therapeutics:Diseases like Parkinson’s, diabetes

Human ES cell lines exist

Fig. 17.24

Embryonic Stem Cells and Therapeutic Cloning

1997 Dolly the sheep cloned: Somatic cell nuclear transfer

process This cloning in mammals is

difficult and inefficient Possible therapeutic cloning

Fig. 17.25

Embryonic Stem Cells and Therapeutic Cloning

Therapeutic cloning: Nucleus from adult human cell

transferred to enucleated egg Resulting embryo cells used to

produce differentiated cells for transplantation therapy.

Bypasses problem of tissue rejection

Problems with therapeutic cloning: Low efficiency of generating embryos

by somatic cell nuclear transfer. Ethical concerns:

• Possible cloning of humans (reproductive cloning),

• destruction of embryos

Fig. 17.26 therapeutic cloning for personalized tissue transplants

Embryonic Stem Cells and Therapeutic Cloning

Induced pluripotent stem cells: Very recent procedures may overcome technical, ethical difficulties

Reprogram somatic cells to resemble embryonic stem cells.

Only 4 key transcription factorsreprogram adult mouse somatic cells

Oct4, Sox2, Klf4, c-Myc) Also adult human fibroblasts

Fig. 17.27