1

complexity

egg sperm

Development

developmental capacitydevelopmental stage

adult differentiated

Progressive restriction

Lecture 10 – Stem cells and regenerative

medicine

Zygote (fertilized egg)

Embryo

Blastocyst

Developmental potential – mammals

2

Differentiated

Developmental potential – plants

Culture leads to dedifferentiation

callus formation

Embryo formation

Differentiated plant cells are totipotent!genomic equivalence

Plant is genetically identical - cloningPlant growth

Lecture 10 – Stem cells and regenerative

medicine

3

Cloning with somatic, differentiated cells

Lecture 10 – Stem cells and regenerative

medicine

4

Stem Cell: undifferentiated, capable of continuous proliferation

Pluripotent: 3 germ layers (endoderm, mesoderm, ectoderm)

Totipotent: all cell types (embryonic & extraembryonic)

Developmental potential – mammals

Asymmetric division

Stem Cell Niche

Lecture 10 – Stem cells and regenerative

medicine

ES cells from ICM

5

Developmental potential – mesenschymal stem cells (MSC) in mammals

Specification of Developmental fates

Distinct gene expression

programs!

Lecture 10 – Stem cells and regenerative

medicine

6

Pluripotent

developmental capacity

Differentiated

Genomic equivalence

multipotent

bonemuscle

nerve

embryonicstem cells

Tissue Rejection

Adult stem cells: skin, intestine, blood… Bone:

a. hematopoieticb. multipotent stromal cells

bone/muscle

Lecture 10 – Stem cells and regenerative

medicine

Therapeutic cloning

Cell/tissue immune compatibility

7

Gene Therapy – direct vs. cell based

Lecture 10 – Stem cells and regenerative

medicine

8

Pluripotent stem cells

Potential usesRepair mutation, reimplant patient cells

OCT4, SOX2, KLF4, MYC

- induce pluripotency • Oct4, SOX2, KLF4, cMyc• genetically corrected iPS cells

- reintroduce cells

- induce cell type desired

- use fibroblast, repair defect

Lecture 10 – Stem cells and regenerative

medicine

9

Pluripotent stem cells 2008 - Eggan labadult fibroblasts - patient matched!OCT4, SOX2, KLF4, MYC

Lecture 10 – Stem cells and regenerative

medicine