Stem cells and cloning: Future challenge BCMB 465 -Stem Cells & Cloning - 11.20.02 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 Bone, Skin, Muscle, Nerves, etc. Embryo growing on irradiated Mouse Embryo Fibroblasts Differentiation directed by growth and differentiation factors (now unknown ) Bone, Skin, Muscle, Nerves, etc.

Major Goals in Developing Transplantation Therapies from Human ES Cell Lines Human ES cells Establish pure cultures of specific cell types Test physiologic function Test methods to prevent rejection Demonstrate efficacy Demonstrate safety 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

“Therapeutic” cloning: Derivation of embryonic stem cells from the patient Solter and Gearhart, Science 1999

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