Stem Cells: Scientific Potential and Alternatives Glenn Sauer, Ph.D. Biology Department Fairfield University.

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Presentation transcript:

Stem Cells: Scientific Potential and Alternatives Glenn Sauer, Ph.D. Biology Department Fairfield University

Scientific Principles What are stem cells? What are stem cells? How are they used? How are they used? What is the potential for therapeutic applications? What is the potential for therapeutic applications? More information: More information:

Review of Terminology DNA - deoxyribonucleic acid, makes up genes DNA - deoxyribonucleic acid, makes up genes Gene - functional unit of heredity, a segment of DNA located at a specific site on a chromosome; genes direct the formation of proteins. Gene - functional unit of heredity, a segment of DNA located at a specific site on a chromosome; genes direct the formation of proteins. Nucleus - a membrane bound structure in the cell which contains the chromosomes. Nucleus - a membrane bound structure in the cell which contains the chromosomes. Cell - the basic unit of life, all living organisms are made up of cells Cell - the basic unit of life, all living organisms are made up of cells somatic cell - a cell of the body (220 types in humans) somatic cell - a cell of the body (220 types in humans) germ cell - an egg or sperm germ cell - an egg or sperm

Differentiation of Human Tissues Early embryonic cells unspecialized Early embryonic cells unspecialized Three primary tissue layers: Three primary tissue layers: Ectoderm Ectoderm Mesoderm Mesoderm Endoderm Endoderm All tissues develop from here All tissues develop from here

Adult Stem Cells Stem cells = cells that have the ability to divide for indefinite periods and give rise to specialized cells Progenitor cells = partially specialized cells that can give rise to particular cell types

Stem Cells of the Bone Marrow

The Problem of Cell Potency Unipotent - cell divides to produce same cell type; most cells Unipotent - cell divides to produce same cell type; most cells Multipotent - can give rise to some cell types; adult stem cells Multipotent - can give rise to some cell types; adult stem cells Pluripotent - able to give rise to most cell types; embryonic, very small number of adult stem cells Pluripotent - able to give rise to most cell types; embryonic, very small number of adult stem cells Totipotent - unlimited cabability; can give rise to all cell types; only in early embryos Totipotent - unlimited cabability; can give rise to all cell types; only in early embryos

Early Embryological Development

Derivation of Human Pluripotent Stem Cells John Gearhart (1998) - embryonic germ (EG) cells cultured from gonadal ridge of 5- to 9-week old fetal tissue obtained from elective abortions. Proc. Natl. Acad. Sci. USA 95: John Gearhart (1998) - embryonic germ (EG) cells cultured from gonadal ridge of 5- to 9-week old fetal tissue obtained from elective abortions. Proc. Natl. Acad. Sci. USA 95: James Thomson (1998) - embryonic stem (ES) cells derived from inner cell mass of blastocysts created through in vitro fertilization procedures and donated for research purposes. Science 282: James Thomson (1998) - embryonic stem (ES) cells derived from inner cell mass of blastocysts created through in vitro fertilization procedures and donated for research purposes. Science 282:

Derivation of hES Cells “Excess” frozen blastocysts donated from fertility clinics “Excess” frozen blastocysts donated from fertility clinics Inner cell mass (embryo) separated from trophoblast (placenta) Inner cell mass (embryo) separated from trophoblast (placenta) Cells dissociated and cultured in laboratory Cells dissociated and cultured in laboratory Can be made to differentiate using chemical signals Can be made to differentiate using chemical signals

Applications of Pluripotent Stem Cells Basic research in human development Basic research in human development “decision-making genes” (birth defects, cancer) “decision-making genes” (birth defects, cancer) Drug development Drug development human cell lines for all cell types human cell lines for all cell types Cell therapies Cell therapies replacement tissue for degenerative conditions (Parkinson’s and Alzheimer’s disease, diabetes, heart disease, stroke, arthritis) replacement tissue for degenerative conditions (Parkinson’s and Alzheimer’s disease, diabetes, heart disease, stroke, arthritis)

Example: Diabetes Insufficient insulin production in pancreas Insufficient insulin production in pancreas Insulin needed for glucose uptake Insulin needed for glucose uptake “Islet-like” cells derived from stem cells produce insulin “Islet-like” cells derived from stem cells produce insulin Eliminates need for insulin injections Eliminates need for insulin injections

Scientific Challenges Remaining Understanding of cellular events that lead to differentiation and specialization Understanding of cellular events that lead to differentiation and specialization Immunologic rejection - Can stem cells be modified to minimize tissue incompatibility? Immunologic rejection - Can stem cells be modified to minimize tissue incompatibility? Time of development and expense of treatments Time of development and expense of treatments

Rejection: Possible Solutions Genetic engineering Genetic engineering Somatic cell nuclear transfer (SCNT) Somatic cell nuclear transfer (SCNT) develops into a blastocyst develops into a blastocyst Dolly the sheep Dolly the sheep cloning (banned by Congress) cloning (banned by Congress)

The Controversy Tremendous potential Tremendous potential scientific community scientific community medical profession medical profession patient advocates patient advocates Religious/ethical conflict Religious/ethical conflict human dignity human dignity abortion issue abortion issue

When does “Human” Life Begin? Genetic view - at conception (fertilization) Genetic view - at conception (fertilization) Embryologic view - after 14 days when each embryo can produce only one individual Embryologic view - after 14 days when each embryo can produce only one individual Mental activity view - after 25 weeks when the human-specific EEG can be measured (death is defined as the loss of EEG) Mental activity view - after 25 weeks when the human-specific EEG can be measured (death is defined as the loss of EEG) Birthday view - life begins when infant is “metabolically” independent of mother Birthday view - life begins when infant is “metabolically” independent of mother

The Bush Decision - Aug 9, 2001 “We must proceed with great care” - limited approval for ongoing research. Fully funded: adult stem cells, umbilical cord Fully funded: adult stem cells, umbilical cord Restricted: embryonic (existing cell lines only) Restricted: embryonic (existing cell lines only) 64 existing lines 64 existing lines 20 in United States 20 in United States Sweden, India, Australia, Israel Sweden, India, Australia, Israel Unfunded: new donor embryos, cloned embryos Unfunded: new donor embryos, cloned embryos Total federal funding for 2001: $ 250 M

Reaction to Bush Decision Scientists Scientists some $$ better than none some $$ better than none 64 cell lines not enough 64 cell lines not enough concerns about control concerns about control Conservative Christians Conservative Christians relief that more research is not allowed relief that more research is not allowed broken campaign promise broken campaign promise Patient Advocates Patient Advocates cautious optimism cautious optimism emotional pleas for more $$ emotional pleas for more $$

Religions Ponder the Issue Roman Catholic, Evangelical Christians - opposed since stem cells are derived from the destruction of embryos Roman Catholic, Evangelical Christians - opposed since stem cells are derived from the destruction of embryos Most groups do not have official positions Most groups do not have official positions Most common positions: Most common positions: Judaism - supportive since it serves a common good (fighting disease) Judaism - supportive since it serves a common good (fighting disease) Muslim - abortion is wrong but life begins when fertilized egg touches womb Muslim - abortion is wrong but life begins when fertilized egg touches womb Presbyterian, UCC - “generally supportive” Presbyterian, UCC - “generally supportive”

State Response California voters approve Proposition 71 which provides $3 Billion for stem cell research (2004) California voters approve Proposition 71 which provides $3 Billion for stem cell research (2004) Other states approve similar measures (Connecticut, Florida, Illinois, Massachusetts, Missouri, New Hampshire, New York, Pennsylvania, Texas, Washington, Wisconsin) Other states approve similar measures (Connecticut, Florida, Illinois, Massachusetts, Missouri, New Hampshire, New York, Pennsylvania, Texas, Washington, Wisconsin)

Stem Cell Research Enhancement Act Would allow use of surplus in vitro fertilization embryos with donor permission (2005) Would allow use of surplus in vitro fertilization embryos with donor permission (2005) Passed House of Representatives ( ) and Senate (63-37) Passed House of Representatives ( ) and Senate (63-37) Vetoed by George Bush (2006) Vetoed by George Bush (2006) Stem Cell Therapeutic and Research Act of 2005 (enacted) Stem Cell Therapeutic and Research Act of 2005 (enacted) Provides funds for adult stem cell therapies and umbilical cord stem cells Provides funds for adult stem cell therapies and umbilical cord stem cells

Current Situation Barack Obama executive order allows research with new stem cell lines (2009) Barack Obama executive order allows research with new stem cell lines (2009) BUT Dickey Amendment to 1995 Appropriations Bill bans funds for human cloning or any research that voluntarily destroys embryos. BUT Dickey Amendment to 1995 Appropriations Bill bans funds for human cloning or any research that voluntarily destroys embryos. RESULT  Research Labs using state funds to create stem cell lines and federal funds to work with the cells RESULT  Research Labs using state funds to create stem cell lines and federal funds to work with the cells

Alternatives to hES Cells Umbilical cord blood Umbilical cord blood Contains hematopoietic and mesenchymal stem cells (lower potency than hES) Contains hematopoietic and mesenchymal stem cells (lower potency than hES) Patient specific Patient specific Cord blood banks Cord blood banks $2000 collection and $125/year storage fees $2000 collection and $125/year storage fees Some public banks for donated cells Some public banks for donated cells

Alternatives to hES Cells Induced Pluripotent Stem Cells (iPS) Induced Pluripotent Stem Cells (iPS)

Alternatives to hES Cells Induced Pluripotent Stem Cells (iPS) Induced Pluripotent Stem Cells (iPS) Uses Oct4, Sox2, Klf4 and c-Myc genes Uses Oct4, Sox2, Klf4 and c-Myc genes Show higher potency than cord cells Show higher potency than cord cells Low efficiency (recent improvements) Low efficiency (recent improvements) Other problems Other problems Abnormal aging Abnormal aging Tumor production Tumor production Incomplete reprogramming Incomplete reprogramming

Alternatives to hES Cells Direct Cell Reprogramming Direct Cell Reprogramming Turns one cell directly into another Turns one cell directly into another (ex. Skin cell  Neuron) (ex. Skin cell  Neuron) Uses mRNA, no viral vector Uses mRNA, no viral vector Eliminates need for stem cells Eliminates need for stem cells Potential and problems are uncertain Potential and problems are uncertain

Autologous Stem Cell Therapies Self-donation of mesenchymal stem cells Self-donation of mesenchymal stem cells Injected (with or without chemical treatment) into injury site Injected (with or without chemical treatment) into injury site Not FDA approved Not FDA approved Clinical trials underway (heart attack, spinal cord injury, etc.) Clinical trials underway (heart attack, spinal cord injury, etc.) Many Americans seek overseas options Many Americans seek overseas options No proven effectiveness No proven effectiveness Costly Costly High pressure sales tactics High pressure sales tactics

Questions? The United States has been criticized by some for being too restrictive to stem cell-based research and therapies. Should U.S. laws be relaxed to be more accommodating to those wishing treatment? The United States has been criticized by some for being too restrictive to stem cell-based research and therapies. Should U.S. laws be relaxed to be more accommodating to those wishing treatment? A recent study by Duke University predicted that by the year 2050, regenerative procedures based on stem cell and other biotechnologies could extend an average human life span by up to 100 years. Is this a desirable goal? A recent study by Duke University predicted that by the year 2050, regenerative procedures based on stem cell and other biotechnologies could extend an average human life span by up to 100 years. Is this a desirable goal? Many biotechnologies are vastly expensive, yet much of the basic research supporting these developments is paid for by taxpayers. Who should benefit? Many biotechnologies are vastly expensive, yet much of the basic research supporting these developments is paid for by taxpayers. Who should benefit?