麻省理工大学：《生物材料——组织交互作用》教学讲义（英文版）CELLS FOR TISSUE

Massachusetts Institute of Technology yE图 Harvard medical school Brigham and women's hospital VA Boston Healthcare System 2.79J3.96JBE,441/HST522J TISSUE ENGINEERING STEM CELLS I.V.Yannas, Ph. D, and M. Spector, Ph D

Massachusetts In Massachusetts Institute of Technology stitute of Technology Harvard Medical School Harvard Medical School Brigham and Wo Brigham and Women’s Hospital men’s Hospital VA Boston Healthcare System VA Boston Healthcare System 2.79J/3.96J/BE.441/HST522J 2.79J/3.96J/BE.441/HST522J TISSUE ENGINEERING: TISSUE ENGINEERING: STEM CELLS STEM CELLS I.V. Yannas, Ph.D. and M. Spector, Ph.D. I.V. Yannas, Ph.D. and M. Spector, Ph.D

CELLS FOR TISSUE ENGINEERINGREGENERATIVE MEDICINE ° Autologous Differentiated parenchymal cells of same or other tissue type Stem cells(adult) Allogeneic Same as above Fetal stem cells Embryonic stem cells

CELLS FOR TISSUE CELLS FOR TISSUE ENGINEERING/REGENERATIVE MEDICINE ENGINEERING/REGENERATIVE MEDICINE • Autologous Autologous –Differentiated parenchymal cells of same or Differentiated parenchymal cells of same or other tissue type other tissue type – Stem cells (adult) Stem cells (adult) • Allogeneic Allogeneic – Same as above Same as above –Fetal stem cells Fetal stem cells –Embryonic stem cells Embryonic stem cells

WHAT ARE STEM CELLS? Cells with the capacity for unlimited or prolonged self-renewal. Cells that can produce at least one type of highly differentiated descendant

WHAT ARE STEM CELLS? WHAT ARE STEM CELLS? • Cells with the capacity for unlimited or Cells with the capacity for unlimited or prolonged self prolonged self-renewal. renewal. • Cells that can produce at least one type of Cells that can produce at least one type of highly differentiated descendant. highly differentiated descendant

http://www.nih.gov/news/stemcell/primer.htm NATIONAL INSTITUTES OF HEALTH May 2000 Stem Cells: A Primer Definitions Stem cells -cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Multipotent -giving rise to many cell types. Pluripotent-capable of giving rise to most tissues of an organIsm. Totipotent -having unlimited capability. Totipotent cells have the capacity to specialize into extraembryonic membranes and tissues, the embryo, and all postembryonic tissues and organs

http://www. http://www.nih.gov/news/stemcell stemcell/primer. /primer.htm NATIONAL INSTITUTES OF HEALTH NATIONAL INSTITUTES OF HEALTH May 2000 May 2000 Stem Cells: A Primer Stem Cells: A Primer Definitions Definitions Stem cells Stem cells - cells that have the ability to divide for indefinite cells that have the ability to divide for indefinite periods in culture and to give rise to specialized cells. periods in culture and to give rise to specialized cells. • Multipotent Multipotent -giving rise to many cell types. giving rise to many cell types. • Pluripotent Pluripotent -capable of giving rise to most tissues of an capable of giving rise to most tissues of an organism. organism. • Totipotent Totipotent - having unlimited capability. having unlimited capability. Totipotent Totipotent cells have the capacity to specialize into have the capacity to specialize into extraembryonic extraembryonic membranes and tissues, the embryo, and all postembryonic membranes and tissues, the embryo, and all postembryonic tissues and organs. tissues and organs

Pluripotent stem cells undergoLnttp://www.nih.gov/news/stemcell/primer.htm further specialization into stem cells that are committed to give rise to cells that have a particular function. These more specialized tem cells are called multipotent Totipotent Cells Multipotent stem cells are also found in adults. For example, the blood stem cell perform the critical role of continuall Pluripotent Stem Cell replenishing our supply of blood cells Blood Stem Cells Other committed Stem Cells Specialized Red Blood White Blood Cells Cells Platelets

• Pluripotent stem cells undergo further specialization into stem cells that are committed to give rise to cells that have a particular function. These more specialized stem cells are called multipotent. • Multipotent stem cells are also found in adults. For example, the blood stem cell perform the critical role of continually replenishing our supply of blood cells . http://www.nih.gov/news/stemcell/primer.htm

How are pluripotent stem cells derived? Pluripotent stem cells can be isolated directly from the inner cell mass of human embryos at the blastocyst stage and cultured to produce a pluripotent stem cell line. Pluripotent stem cells can be isolated from fetal tissue obtained from terminated pregnancies. Cells can be taken from the region of the fetus that is destined to develop into the testes or the ovaries http://www.nih.gov/news/stemcell/primer.htm

How are pluripotent stem cells derived? How are pluripotent stem cells derived? • Pluripotent stem cells can be isolated directly Pluripotent stem cells can be isolated directly from the inner cell mass of human embryos at from the inner cell mass of human embryos at the blastocyst blastocyst stage and cultured to produce a stage and cultured to produce a pluripotent stem cell line. pluripotent stem cell line. • Pluripotent stem cells can be isolated from fetal Pluripotent stem cells can be isolated from fetal tissue obtained from terminated pregnancies. tissue obtained from terminated pregnancies. Cells can be taken from the region of the fetus Cells can be taken from the region of the fetus that is destined to develop into the testes or the that is destined to develop into the testes or the ovaries. ovaries. http://www.nih.gov/news/stemcell/primer.htm

http://www.nih.gov/news/stemcellprimer.htm Potential Applications of pluripotent Stem cells Help to understand the events that occur during development. identification of the factors involved in the cell specialization; decision-making"genes Change the way drugs are developed and tested for safety. new medications could be initially tested using human cell lines Generation of cells and tissue that could be used for so-called cell therapies. donated organs and tissues are often used to replace ailing or destroyed tissue. the number of people suffering from these disorders far outstrips the number of organs available for transplantation

http://www.nih.gov/news/stemcell/primer.htm Potential Applications of Pluripotent Potential Applications of Pluripotent Stem Cells Stem Cells • Help to understand the events Help to understand the events that occur during development. that occur during development. – identification of the factors involved in the cell identification of the factors involved in the cell specialization; "decision specialization; "decision -making" genes . making" genes . • Change the way drugs are developed and tested for safety. Change the way drugs are developed and tested for safety. – new medications could be initially tested using human cell new medications could be initially tested using human cell lines. • Generation of cells and tissue that could be used for so Generation of cells and tissue that could be used for so -called "cell therapies." "cell therapies." – donated organs and tissues are often us donated organs and tissues are often used to replace ailing ed to replace ailing or destroyed tissue. or destroyed tissue. – the number of people suffering from these disorders far the number of people suffering from these disorders far outstrips the number of organs available for outstrips the number of organs available for transplantation. transplantation

http://www.nih.gov/news/stemcellprimer.htm Adult stem cells Multipotent stem cells can be found in some types of adult tissue. In fact, stem cells are needed to replenish the supply cells in our body that normally wear out(e.g, the blood stem cell). Multipotent stem cells have not been found for all types of adult tissue, but discoveries in this area of research are Increasing. neuronal stem cells have been isolated from the rat and mouse nervous systems. The experience in humans is more limited a kind of cell that may be a neuronal stem cell has been isolated from adult brain tissue

http://www.nih.gov/news/stemcell/primer.htm Adult Stem Cells Adult Stem Cells • Multipotent stem cells can be found in some types of Multipotent stem cells can be found in some types of adult tissue. In fact, stem cells are needed to replenish adult tissue. In fact, stem cells are needed to replenish the supply cells in our body that normally wear out ( the supply cells in our body that normally wear out (e.g., the blood stem cell). the blood stem cell). • Multipotent stem cells have not been found for all types Multipotent stem cells have not been found for all types of adult tissue, but discoveries in this area of research are of adult tissue, but discoveries in this area of research are increasing. increasing. – neuronal stem cells have been isolated from the rat neuronal stem cells have been isolated from the rat and mouse nervous systems. The experience in and mouse nervous systems. The experience in humans is more limited. humans is more limited. – a kind of cell that may be a neuronal stem cell has a kind of cell that may be a neuronal stem cell has been isolated from adult brain tissue. been isolated from adult brain tissue

Do adult stem cells have the same potential as pluripotent stem cells blood stem cells could change course and produce cellsas Until recently, little evidence that multipotent cells such other than a blood stem cell or a specific type of blood cell. In animals. it has been shown that some adult stem cells are able to develop into other types of specialized cells. In mice neural stem cells placed into the bone marrow appeared to produce a variety of blood cell types. In rats, stem cells found in the bone marrow were able to produce liver cells Even after a stem cell has begun to specialize, the adult stem cell may, under certain conditions, be more flexible than first thought http://www.nih.gov/news/stemcell/primer.htm

Do adult stem cells have the same stem cells have the same potential as pluripotent stem cells? potential as pluripotent stem cells? • Until recently, little evidence th Until recently, little evidence that multipotent cells such as at multipotent cells such as blood stem cells could change course and produce cells blood stem cells could change course and produce cells other than a blood stem cell or a specific type of blood cell. other than a blood stem cell or a specific type of blood cell. – – In animals, it has been shown th In animals, it has been shown that some adult stem cells are abl adult stem cells are able to develop into other types of specialized cells. develop into other types of specialized cells. – – In mice neural stem In mice neural stem cells placed cells placed into the bone marrow appeared t into the bone marrow appeared to produce a variety of blood cell types. produce a variety of blood cell types. – – In rats, stem cells found in the bone marrow were able to produc In rats, stem cells found in the bone marrow were able to produce liver cells. liver cells. • Even after a stem cell has begun to specialize, the adult Even after a stem cell has begun to specialize, the adult stem cell may, under certain conditions, be more flexible stem cell may, under certain conditions, be more flexible than first thought. than first thought. http://www.nih.gov/news/stemcell/primer.htm

Why not just pursue research with adult stem cells? Multipotent cells have great potential for use in cell therapies with the following advantages. Transplantation of ex vivo-manipulated autologous cells would not likely result in rejection. Reduce or even avoid the practice of using stem cells derived from human embryos or human fetal tissue sources that trouble many people on ethical grounds. http://www.nih.gov/news/stemcell/primer.htm

Why not just pursue research with Why not just pursue research with adult stem cells? adult stem cells? • Multipotent cells have great potential for use in cell Multipotent cells have great potential for use in cell therapies with the following advantages. therapies with the following advantages. – Transplantation of Transplantation of ex vivo ex vivo -manipulated autologous manipulated autologous cells would not likely result in rejection. cells would not likely result in rejection. – Reduce or even avoid the practice of using stem cells Reduce or even avoid the practice of using stem cells derived from human embryos or human fetal tissue, derived from human embryos or human fetal tissue, sources that trouble many people on ethical grounds. sources that trouble many people on ethical grounds. http://www.nih.gov/news/stemcell/primer.htm