Stem cells and cloning: Future challenge

Stem cells are multi-, pleuri- or totipotent Stem cell derivation: from embryos, from

germ cells or from tissues Cloning of mammals is fraught with

problems and, generally, does not work– outlook for “therapeutic” cloning far better

than that for “reproductive” cloning

Embryonic stem cells Derived from pre-implantation embryo Have ability to be maintained without

differentiating, but: how long??? Appear to have developmental potential to form

all kinds of tissues, but: how is this controlled???

Embryonic Stem Cells

Embryo

Embryonic Stem Cells growing on irradiatedMouse Embryo FibroblastsDifferentiation

directed by growth and differentiation factors (now unknown )

Bone, Skin, Muscle, Nerves, etc.

Major Goals in Developing Transplantation Therapies from Human ES Cell Lines

Establish pure cultures of specific cell types

Human ES cells

Test physiologic function

Demonstrate efficacy Demonstrate safety Test methods to prevent rejection

Human Trials

Basic strategy for cloning of organisms Remove oocyte nucleus (what epigenetic

information is lost?) Replace with nucleus of somatic cell of

individual to be cloned (can somatic nucleus be “reprogrammed” to gametic state?)

Activate development (can somatic nucleus support development in entirety? Or has it lost totipotency?)

Transfer blastocyst to uterus of surrogate mother

Survival curve: Cloned embryos

Solter and Gearhart, Science 1999

“Therapeutic” cloning: Derivation of embryonic stem cells from the patient

Bush stem cell policy - 2001

Federal government will fund research on human embryonic stem cells

However, only stem cell lines derived before 9 August 2001 may be used– 60 lines asserted to be available– much question and controversy about

availability and utility of the 60 lines

Stem cell policies around the world No human embryo research permitted

– Germany, France, Switzerland, Norway, Ireland, Austria, Poland, Brazil

Use of already-derived stem cells permitted, but not the derivation– US

Both derivation and use of stem cells from spare embryos permitted– Japan, Canada, Spain, Italy, Finland, Sweden, Israel, Singapore,

Australia

Derivation and use of stem cells from embryos created for research permitted– United Kingdom, privately funded researchers in the US, de facto

policy in China