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1 : 1 Concept of Stem Cells: Embryonic and Adult Stem Cells ) (Totipotent stem cell) 2) (Pluripotent stem cell) 3) (Multipotent stem cell) 3. (Embryonic stem cells) (Adult stem cells) ,., 35,000.,, 210. (stem cell) (embryonic stem cell) , : 13

2 Fig. 1. Development of embryonic stem cells from the differentiated cells of an adult.., (Fig. 1). ( ; totipotent),,... 2., (self-renewal), (Table 1).,, (Fig. 2). 14

3 Table 1. Capability of stem cell i) Proliferation ii) Self-renewal iii) Production of a large number of differentiated progeny iv) Regeneration and maintainence of tissues Fig. 2. Human stem cells. (totipotent stem cell). (blastocyst)..,. (pluripotent stem cells),, (Table 2). : 15

4 Table 2. Stem cells and organogenesis during embryonic development Germ layer Endoderm Mesoderm Ectoderm Differentiated organ/tissue Thymus Thyroid, parathyroid glands Epithelial lining of larynx, trachea, lung, respiratory tract Epithelial lining of urinary bladder, vagina, urethra Liver, pancreas, lining of gastrointestinal tract Cardiac, skeletal and smooth muscle Heart and blood vessels Bone marrow (blood) Lymphatic tissue Connective tissues, e.g. bone, cartilage, fibroblast, lipocyte Adrenal cortex Urogenital system Skin Neural tissue Adrenal medulla Pituitary gland Eyes, ears, connective tissue of head/face (hematopoietic stem cells),,, (multipotent stem cells).. 2,000, 100, 4,000. (totipotent stem cells) (pluripotent stem cells), (multipotent stem cells) (Fig. 2). 1) (Tot ipote nt ste m ce ll),. ( ). 16

5 (Fig. 2) ) (Pluripote nt ste m ce ll) (blastocyst) inner cell mass (ICM). ICM (trophoblast). ICM, ICM (pleuripotency). ICM,., 1998 Thomson.,. 3 ) (Multipote nt ste m cell),.,,. (hematopoietic stem cell),..,. (Table 3). (hematopoietic stem cell), (neural stem cell), (mesenchymal stem : 17

6 Table 3. Companies for stem cell research and development Company Location Specialization Aastrom Biosciences Geron Corp. Layton BioScience Neural Stem Biopharmaceuticals Neuronyx Inc Nexell Therapeutics Inc. Osiris Therapeutics ReNeuron Stem Cell Sciences 6Stem Cells Inc. Ann Arbor, MI Menlo Park, CA Atherton, CA Bethesda, MD Malvern, PA irvine, CA Baltimore, MD London Melbourne, Australia Sunnyvale, CA Hematopoietic stem cells Embryonic, fetal stem cells Fetal neural stem cells Fetal neural stem cells Neural stem cells Hematopoietic stem cells Mesenchymal stem cells Neural stem cells Embronic stem cells Adult neural stem cells cell).,,.,,.. Table 4. Markers for tissue- specific stem cells Organ Stem cell type Markers Bone marrow Brain Cornea Gut Heart Liver Lung Breast Pancreas Retina Skin Testes HSC MSC NSC/ependymal cells Corneal epithelial stem cells Intestinal stem cells No known stem cell Oval cells Likely to exist Mammary epithelial stem cells Pancreatic stem cells Retinal stem cells Epidermal stem cells Spermatogonial stem cells Mouse: Sca-1, c-kit, CD34: Human: KDR, CD34 Human: SH2 +, SH3 +, CD34 -, CD45 - Nestin, Notch-1 No known specific markers No known specific markers Rat: OV6, OC2, OC3, Thy-1, c-kit, CD34 Unknown Human: CALLA, MUC1 Mouse: Nestin, Neurogenin-3 Mouse and chicken: Nestin, CHX-10 Mouse: 6 bri, CD71 dim 6- and 1-integrin 18

7 ,.,,,,,,.,,,,,. (marker) (Table 4). 3. (embryonic stem cells) (adult stem cells). (embryo) 8 (Fig. 3) ,,. Fig. 3. Development of embryonic and adult stem cells : 19

8 Table 5 20

9 (Fig. 3).,. (Table 5)., (cord boold),. (Table 6). Table 6. Differences between embryonic and adult stem cells Feature Embryonic stem cells Adult stem cells Source Develop in tissue culture (in vitro) from inner cell of early embryo mass Exist in many tissue sin adult human body (in vivo) Abundance in tissues High Very low-difficult to identify, isolate and purify Ability to spontaneously differentiate Yes, in favourable tissue culture conditions Not observed, some circumstantial evidence, e.g. in the olfactory bulb Pluripotency High, i.e. can form all cells of the body Low, e.g. haematopoietic and gut Capacity to specialize into various cell and tissue types High-can develop into specialized cells from all three embryonic layers Limited-increasing evidence, e.g. bone marrow cells developing into liver cells, neurons 4. in vitro model. : 21

10 ,.,,. (Fig. 4).,.,,.., 1..,,.,, Heart disease (e.g. replace muscle and arteries) Spinal cord injuries (e.g. replace nerve cells) Burn injuries (e.g. provide new skin tissue) Stem cells Parkinson's disease (e.g. replace nerve cells) Alzheimer's disease (e.g. replace damaged nerve cells) Type-1 diabetes (e.g. add healthy pancreatic cells) Fig. 4. Therapeutic use of stem cells in human disease 22

11 .,.,..,..,. 5. in vivo. in vivo. NIH McKay 1997,,, bfgf EGF embryoid body PDGF. embryoid body in vitro Washington Choi McDonald. (retinoic acid) embryoid body.,.. Rhesus monkey, 1995 Rhesus monkey. (cell therapy).,. : 23

12 . NIST Osiris Therapeutics 2...,,,.. Ahrendt SA, Decker PA, Doffek K, Wang B, Xu L, Demeure MJ, Jen J, Sidransky D. Microsatellite instability at selected tetranucleotide repeats is associated with p53 mutations in non-small cell lung cancer. Cancer Res, 2000, 60, Barinaga M. Fetal neuron grafts pave the way for stem cell therapies. Science, 2000, 287, Bjorklund A. The use of neural stem cells for gene therapy in the central nervous system. J Gene Med, 1999, 1, Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL. Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science, 1999, 283, Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, Duncan ID, McKay RD. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science, 1999, 285, Brustle O, Spiro AC, Karram K, Choudhary K, Okabe S, McKay RD. In vitro-generated neural precursors participate in mammalian brain development. Proc Natl Acad Sci USA, 1997, 94, Evans MJ, Kaufman MH. Establishment in culture of pluripotential cells from mouse embryos. Nature, 1981, 292, Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, Snyder EY. Engraftable human neural stem cells respond to developmental 24

13 cues, replace neurons, and express foreign genes. Nat Biotechnol, 1998, 16, Fricker RA, Carpenter MK, Winkler C, Greco C, Gates MA, Bjorklund A. Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain. J Neurosci, 1999, 19, Gage FH, Ray J, Fisher LJ. Isolation, characterization, and use of stem cells from the CNS. Annu Rev Neurosci, 1995, 18, Gage FH. Mammalian neural stem cells. Science, 2000, 287, Jackson KA, Majka SM, Wulf GG, Goodell MA. Stem cells: a minireview. J Cell Biochem Suppl, 2002, Suppl 38, 1-6. Keller R. Stem cells on the way to restorative medicine. Immunol Lett, 2002, 83, Lindvall O. Engineering neurons for Parkinson's disease. Nat Biotechnol, 1999, 17, Lindvall O. Neural transplantation: a hope for patients with Parkinson's disease. Neuroreport, 1997, 8, Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci USA, 1981, 78, McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI, Choi DW. Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med, 1999, 5, Olanow CW, Kordower JH, Freeman TB. Fetal nigral transplantation as a therapy for Parkinson's disease. Trends Neurosci, 1996, 19, Panchision D, Hazel T, McKay R. Plasticity and stem cells in the vertebrate nervous system. Curr Opin Cell Biol, 1998, 10, Reubinoff BE, Pera MF, Fong CY, Trounson A, Bongso A. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol, 2000, 18, Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science, 1992, 255, Semsarian C. Stem cells in cardiovascular disease: from cell biology to clinical therapy. Intern Med J, 2002, 32, Shamblott MJ, Axelman J, Wang S, Bugg EM, Littlefield JW, Donovan PJ, Blumenthal PD, : 25

14 Huggins GR, Gearhart JD. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc Natl Acad Sci USA, 1998, 95, Snyder EY, Deitcher DL, Walsh C, Arnold-Aldea S, Hartwieg EA, Cepko CL. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell, 1992, 68, Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science, 1998, 282, Thomson JA, Kalishman J, Golos TG, Durning M, Harris CP, Becker RA, Hearn JP. Isolation of a primate embryonic stem cell line. Proc Natl Acad Sci USA, 1995, 92, van der Kooy D, Weiss S. Why stem cells? Science, 2000, 287, Vogel G. Can old cells learn new tricks? Science, 2000, 287, Wilmut I, Campbell K, Tudge C: The second creation, The age of biological control by the scientists who cloned Dolly Headlind, London, Yandava BD, Billinghurst LL, Snyder EY. "Global" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci USA, 1999, 96,

Osteoblast Progenitor Cells Derived from Umbilical Cord Blood 167 μ μ α α μ β μ μ α μ μ μ μ β μ

Osteoblast Progenitor Cells Derived from Umbilical Cord Blood 167 μ μ α α μ β μ μ α μ μ μ μ β μ Differentiation of Osteoblast Progenitor Cells from Human Umbilical Cord Blood Seung-Jin Hong 1, Eun-A Lee 3, Gue-Tae Chae 2 and Hoon Han 1 Departments of 1 Microbiology and Immunology, 2 Pathology, College