STEM CELLS: The Upside STEM CELLS: The Upside and Downside of Stem Cell and Downside of Stem Cell

ScienceScience

Human ES cell colony: picture provided by Dr. Toshihiko Ezashi

StemStem

The main body or stalk of a plant

The stock of a family lineage

Specialized (differentiated) Specialized (differentiated) cellscells

Diploid, with 46 chromosomes

Haploid with 23 chromosomes

Skin stem cell

Neuronal stem cell

Intestinal stem cell

Bone marrow stem cell

The human body consists of more than The human body consists of more than 10 trillion cells of more than 250 cell 10 trillion cells of more than 250 cell

typestypes

What are stem cells?What are stem cells?

A stem cell has the ability to divide for indefinite number of divisions.

Stem cells give rise to more specialized cells when they differentiate.

There are three types of stem cell: unipotent, lineage specific stem cells, “adult” stem cells (multipotent), embryonic stem cells (pluripotent).

Real and Potential Real and Potential Applications of Stem CellsApplications of Stem Cells

Bone marrow transplantation Transplantation medicine (diabetes,

Parkinson’s Disease; stroke, arthritis, multiple sclerosis, heart failure; spinal cord lesions)

Drug testing Genetic change Other uses?

Source: NIH website “Stem cells: A Primer”

UNIPOTENT STEM CELLSUNIPOTENT STEM CELLS

M N H P

ADULT STEM CELLSADULT STEM CELLS

Undifferentiated, multipotent cells found in a differentiated tissue that can

renew themselves and (with certain limitations) differentiate to yield all the specialized cell types of the tissue from which it originated, e.g stem cells from bone marrow that can give rise to all

the blood cell types.

Stem Cells versus Progenitor Stem Cells versus Progenitor CellsCells

Niche Cells

Stem Cells

Progenitor cells

Differentiated Cells

Precursor cells

Source: NIH website “Stem cells: A Primer”

PLURIPOTENT (Adult) PLURIPOTENT (Adult) STEM CELLSSTEM CELLS

Do such cells exist? Where?

Are they an alternative to pluripotent embryonic stem cells?

ADULT STEM CELLSADULT STEM CELLS HAVE BROADHAVE BROAD

THERAPEUTIC POTENTIAL (or do THERAPEUTIC POTENTIAL (or do they?)they?)

ADULT STEM CELLSADULT STEM CELLS HAVE LIMITEDHAVE LIMITED

THERAPEUTIC POTENTIALTHERAPEUTIC POTENTIAL

Embryonic stem cellsEmbryonic stem cells

What’s all the fuss about?

EMBRYONIC STEM CELLSEMBRYONIC STEM CELLS

Primitive (undifferentiated) cells, usually from the embryo, that have

the potential to become a wide variety of specialized cell types.

Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells

From “spare” IVF embryos Therapeutic cloning, i.e. by somatic

cell nuclear transfer Induced pluripotent stem cells

Dominic Doyle

Bob Edwards and Patrick Bob Edwards and Patrick SteptoeSteptoe

Over Three Million IVF and Over Three Million IVF and Thousands of PGD Babies Thousands of PGD Babies

have been Born!have been Born!

SEXUALSEXUAL

REPRODUCTIONREPRODUCTION

HUMAN ES HUMAN ES CELLSCELLS

First isolated in 1998 from spare blastocysts donated by an

In Vitro Fertilization (IVF)program

Source: NIH website “Stem cells: A Primer”

CONCERNCONCERN

Production of new human ES cells will involve the destruction of thousands of human embryos

FactsFacts

Every year hundreds of thousands of human embryos are created by in vitro fertilization procedures designed to allow infertile couples to have children. To obtain eggs for IVF, eggs are produced by “superovulation” procedures

Many more eggs are produced and fertilized than can possibly be used.

Result: embryos are discarded or stored indefinitely.

ARE SUFFICIENT NUMBERS OF ARE SUFFICIENT NUMBERS OF EMBRYONIC STEM CELL LINES EMBRYONIC STEM CELL LINES ADEQUATE FOR DEVELOPING ADEQUATE FOR DEVELOPING

THERAPIES?THERAPIES? Different lines have different properties:

they don’t all behave the same. Existing stem cells will never be useful for

transplantation. Transplantation demands a close “match”

between the donor and the recipient, e.g. kidney transplantation. Hence there is a requirement for large numbers of cell lines with different transplantation antigens on their surfaces.

1.How to direct their differentiation efficiently into specific cell types (e.g. pancreas, brain neurons).

2. How to deliver them efficiently for tissue repair.

3. How to prevent immune rejection.

EMBRYONIC STEM EMBRYONIC STEM CELLS FOR THERAPYCELLS FOR THERAPY

Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells

From “spare” IVF embryos Therapeutic cloning, i.e. by somatic

cell nuclear transfer Induced pluripotent stem cells

NUCLEAR NUCLEAR TRANSPLANTATION TRANSPLANTATION TO PRODUCE STEM TO PRODUCE STEM

CELLSCELLS

February 1997February 1997 Cloning of Dolly reportedCloning of Dolly reported

Somatic Cell Nuclear Transfer Somatic Cell Nuclear Transfer “Reproductive Cloning”“Reproductive Cloning”

SheepCattleGoatMulePigCatMouseRatRabbit

Day 5

“Therapeutic

ABILITY TO PRODUCE ABILITY TO PRODUCE STEM CELLS STEM CELLS

GENETICALLYGENETICALLY

IDENTICAL TO PATIENTIDENTICAL TO PATIENT

HOW DOES THIS RELATE HOW DOES THIS RELATE TO HUMAN CLONING???TO HUMAN CLONING???

CONCERNCONCERN

NUCLEAR TRANSPLANTATION WILL BE

USED TO CLONE HUMAN BABIES.

NUCLEAR NUCLEAR TRANSPLANTATION TO TRANSPLANTATION TO PRODUCE STEM CELLSPRODUCE STEM CELLS

• NO EMBRYONIC OR FETAL DEVELOPMENT BEYOND 200 CELL STAGE (SIZE OF TIP OF PIN)

• NO TRANSFER TO UTERUS• BLASTOCYST OR STEM CELLS ALONE

CANNOT PRODUCE A NEW INDIVIDUAL

CONCERNCONCERN

Production of new human ES cells by somatic cell nuclear transfer will require an unlimited number of human oocytes from women

donors

Day 5

CONCERNCONCERN

HUMAN EGG HUMAN EGG DONORS DONORS

WILL BE EXPLOITEDWILL BE EXPLOITED

Establishment of Human Establishment of Human Embryonic Stem CellsEmbryonic Stem Cells

From “spare” IVF embryos Therapeutic cloning, i.e. by somatic

cell nuclear transfer Induced pluripotent stem cells

Pluripotent stem cells from adult fibroblasts

Nanog; Oct4 (POU domain transcription factor 5); Sox2, sex determining region Y-box 2 (SRY); Klf4 (Kruppel-like factor 4); c-Myc viral oncogene homolog; Lin28 homolog

Lin28Nanog

Takahashi (Yamanaka et al., Cell,2007Yu (Thomson) et al. Science 2007 Diagram from Zhares & Scholer, Cell 2007)

0 2 3-1

GFP-PFF

30

Images of iPPC picked at day 30

20% O24% O2

Thank you

IssuesIssues When does life begin? Missouri statutes

indicate that human life begins at the moment of conception

The new constitutional amendment and what it means

But the sperm and the egg are alive The transition from an embryo to a baby is a

gradual one Are embryos that cannot form a placenta or

that are doomed to die before the differentiation of the main organ systems individuals?

ARE SUFFICIENT ARE SUFFICIENT NUMBERS OF EMBRYONIC NUMBERS OF EMBRYONIC

STEM CELL LINES STEM CELL LINES ADEQUATE FOR ADEQUATE FOR

DEVELOPING THERAPIES?DEVELOPING THERAPIES?

Some QuestionsSome Questions

The status of hES cells. Are they the equivalent of embryos? Persons?

What are the objections to using spare embryos?

Are there alternatives to using hES cell lines for tissue replacement? Adult stem cells?

Can hES cells be produced by developing cell lines from a biopsy of an embryo?

Can embryos be created that lack any potential to develop into babies?