Appendix D: Stem Cell Tables

Compendium of Scientific Publications Regarding the Isolation and Characterization of Stem Cells

The following tables provide an overview of information about stem cells that have been derived from mice and humans. The tables summarize published research that characterizes cells that are capable of developing into cells of multiple germ layers (i.e., multipotent or pluripotent) or that can generate the differentiated cell types of another tissue (i.e., plasticity) such as a bone marrow cell becoming a neuronal cell. The tables do not include information about cells considered progenitor ore precursor cells or those that can proliferate without the demonstrated ability to generate cell types of other tissues.

The tables list the tissue from which the cells were derived, the types of cells that developed, the conditions under which differentiation occurred, the methods by which the cells were characterized, and the primary references for the information.

Appendix D.i. Published Reports on Isolation and Differentiation of Mouse Stem Cells
Origin		Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Tissue	Cell Type	Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Bone marrow	Hematopoietic stem cell (HSC)	Cardiac muscle	Cardiac injury induced in mice Injected labeled HSCs into injured heart	Measurement of green fluorescent protein (GFP) in regenerating cardiac cells Measurement of cardiac-specific protein and gene expression Cardiac-function tests	Orlic et al., 2001
	HSC	Epithelial cells of the liver, skin, lung, esophagus, stomach, small and large intestine	Transplantation of HSCs into lethally irradiated female mice	Detection of antibodies to cellular and cell-surface proteins Cell staining Probing for Y chromosome-positive cells	Krause et al., 2001
	HSC	Cholangiocyte Hepatocyte	Purification of HSCs from bone marrow Transplantation of HSCs into mice with liver-enzyme deficiency	Observation of normalized liver function and regenerating hepatocytes Measurement of expression of hematopoietic and hepatic cell-surface proteins	Lagasse et al., 2000
	HSC	Platelet Red blood cell White blood cell	Hematopoietic growth factors: interleukin-3, interleukin-6, granulocyte-colony stimulating factor, erythropoietin, and thrombopoietin	Detection of antibodies to cell-surface proteins Colony-forming assays Immunophenotyping	Spangrude et al., 1991 Morrison et al., 1995
	HSC Side population (SP)	Skeletal muscle	Lethal irradiation of female mice Induced muscle injury Purified bone marrow transplanted into mice	Measurement of dystrophin expression in regenerating muscle cells Fluorescence-activated cell sorting (FACS) Probing for Y chromosome-positive cells	Gussoni et al., 1999
	Mesenchymal stem cell (MSC)	Adipocyte Chondrocyte Osteoblast Tenocyte	Dexamethasone Vitamin D₃ Bone morphogenetic protein-2 (BMP-2)	Detection of antibody binding to cell-surface proteins Immunofluorescence	Friedenstein et al., 1976 Pereira et al., 1995 Prockop, 1997
	MSC	Astrocyte Neuron	Injection of MSC into brain of immunocompromised neonatal mice	Detection of cell-surface markers by using antibodies and immunofluorescence	Kopen et al., 1999
	MSC	Astrocyte Neuron	Epidermal growth factor Brain-derived neurotrophic factor β-mercaptoethanol Retinoic acid	Immunofluorescence Cell sorting	Sanchez-Ramos et al., 2000
	MSC	Neuron	Stromal cells expanded as undifferentiated cells β-mercaptoethanol Butylated hydroxyanisole	Detection of numerous neuron-specific proteins via staining	Woodbury et al., 2000
	MSC	Skeletal muscle	5-azacytidine and amphotericin B	Observation of myotubes Staining for myocytes	Wakitani et al., 1995
	MSC and/or HSC	Astrocyte Microglia Oligodendrocyte	Induced injury to neural tissue Bone marrow transplantation	Detection of antibodies to cell-surface proteins	Eglitis and Mezey, 1997
	MSC and/or HSC	Cardiac muscle	Bone marrow transplantation of 5-azacytidine-treated cells into mice with induced cardiac muscle injury	Cell staining for cardiac muscle proteins Measurement of blood pressure Electron microscopy Observation of beating cells in vitro Measurement of atrial natriuretic peptide Staining cells for muscle proteins	Tomita et al., 1999 Makino et al., 1999
	MSC and/or HSC	Hepatocyte	Suppression of liver cell proliferation Induced injury to liver Bone marrow transplantation	Staining cells Antibody labeling of cell-surface markers	Taniguchi et al., 1996 Petersen et al., 1999 Theise et al., 2000
	MSC and/or HSC	Neuron	Induced neural tissue injury Bone marrow transplantation into female mice	Detection of antibodies to cell-surface proteins Probing for Y chromosome-containing neurons	Mezey et al., 2000 Brazelton et al., 2000
	MSC, HSC, or side population (SP)	Cardiac muscle Skeletal muscle	Lethal irradiation of mice Bone marrow transplantation from normal male donor mice into mice with induced muscle degeneration	Probing for Y chromosome-containing muscle cells Detection of expression of myoregulatory proteins	Bittner et al., 1999
	MSC, HSC, or SP	Skeletal muscle	Induced muscle tissue injury Transplantation of genetically marked bone marrow into immunodeficient mice	Histologic observation of muscle regeneration Detection of antibodies to cell-surface proteins Myogenic differentiation factor transcript expression	Ferrari et al., 1998
	SP	Cardiomyocyte Vascular endothelia	Transplanted into lethally irradiated mice with ischemic damage to cardiac tissue	Immunohistochemistry Staining for cardiomyocte marker (alpha-actin) and endothelial marker (flt-1)	Jackson et al., 2001
Brain	Neural stem cell (NSC)	Astrocyte Neuron Oligodendrocyte	Basic fibroblast growth factor Epidermal growth factor	Detection of antibodies to neural cell-specific proteins	Reynolds et al., 1996 Doetsch et al., 1999 Johansson et al., 1999
	NSC	Red blood cell White blood cell	Transplantation of NSC into irradiated mice	Flow cytometry analysis Genetic labeling assay Detection of antibodies to cell surface proteins	Bjornson et al., 1999
	NSC	Skeletal muscle	Transplantation of NSCs into mice In vitro co-culture with myogenic cells	Observation of differentiated skeletal muscle cells Analysis of muscle cell-specific proteins and gene expression	Galli et al., 2000
Embryoblastocyst inner-cell mass	Embryonic stem (ES)	Adipocyte	Retinoic acid Insulin, T3 (thyroid hormone), and Leukemia inhibitory factor (LIF)	Observation of adipocyte differentiation Measurement of adipocyte enzyme activity Measurement of adipocyte-specific gene expression	Dani et al., 1997
	ES	Astrocyte Glial precursor Oligodendrocyte	Cells cultured in neurogenic medium with basic fibroblast growth factor Epidermal growth factor Platelet-derived growth factor Transplanted glial precursor cells into myelin-deficient mice	Observation of spinal cord remyelination Electron microscopy Antibodies to neural cell-specific proteins	Brustle et al., 1999
	ES	Astrocyte Midbrain neuron Neural precursor Neuron Oligodendrocyte	Retinoic acid Cell selection through transgene conferring drug resistance Co-culture with stromal cells	Examination of cell morphology and neuron-specific markers Cell-specific markers Detection of dopamine production	Bain et al., 1995 Strubing et al., 1995 Li et al., 1998 Lee et al., 2000 Kawasaki et al., 2000
	ES	Astrocyte Neuron Oligodendrocyte	Retinoic acid	Observation of functional synapses Measurement of neurotransmitters	Slager, et al., 1993 Gottlieb, et al., 1999
	ES	Astrocyte Oligodendrocyte	Retinoic acid Fetal calf serum (10%) β-mercaptoethanol	Antibodies to neural cell-specific proteins Cytochemistry	Fraichard et al., 1995
	ES	Cardiac muscle Skeletal muscle Smooth muscle	Retinoic acid Dimethyl sulfoxide Transplantation of muscle cells into mice	Histology Detection of cell-specific proteins Cytochemistry	Dinsmore et al., 1996
	ES	Cardiomyocyte	LIF, retinoic acid Fibroblast feeder cells	Histology and observation of beating cardiomyocyte Detection of specific cardiac cell-gene expression and cardiomyocyte surface proteins	Doetschman et al., 1985 Maltsev et al., 1993 Wobus et al., 1995
	ES	Cardiomyocyte	LIF Cell selection through genetic labeling of ES Injection of ES into mouse heart	Detection of genetically labeled cardiomyocytes Electrophysiological studies	Bader et al., 2000
	ES	Cardiomyocyte	LIF Purification of cardiomyocytes from ES culture by genetic labeling and selection	Observation of functional cardiomyocyte grafts in heart Immunohistology	Klug et al., 1996
	ES	Cardiomyocyte	Culture of ES with LIF Selection of cardiomyocytes through genetic labeling Injection of cardiomyocytes into mouse heart	Microscopy and cell receptor studies Observation of cardiomyocyte differentiation and contractility Analysis of cardiomyocyte gene expression	Westfall et al., 1997
	ES	Chondrocyte (cartilage-forming cell)	BMP-2 and BMP-4	Staining of mature chondrocytes Measurement of chondrocyte-specific gene expression and proteins	Kramer et al., 2000
	ES	Dendritic (immune cell)	Culture on stromal cell layer Interleukin-3 Granulocyte-macrophage stimulating factor	Immune-function assays Immunophenotyping	Fairchild et al., 2000
	ES	Embryoid bodies (EBs) consisting of structures that contain tissues of the three embryonic germ layers: endoderm, mesoderm, and ectoderm Teratocarcinoma	ES cultured in suspension without feeder cell layer Absence of LIF Injection of ESs into mice	Observation of differentiation into multiple tissue types of the germ layers of blood, skeletal and cardiac muscle, primitive gastrointestinal and neural tissue Growth of tumor containing tissues from embryonic germ layer	Evans and Kaufman, 1981
	ES	ES self-renewal	LIF Culture on feeder cell layer	Observation of extensive ES proliferation and self-renewal	Evans and Kaufman, 1981
	ES	Endothelial	Culture on collagen substrate Hematopoietic growth factors Semisolid media EB implanted peritoneal cavity	Observation of capillary formation	Risau et al., 1988
	ES	Endothelial Smooth muscle Vascular progenitor	Culture over collagen-IV matrix Absence of LIF Vascular endothelial growth factor	Electron microscopy: observation of endothelial and smooth muscle vascular structures Detection of endothelial cell marker by immunochemistry Detection of smooth muscle markers by immunochemistry	Yamashita et al., 2000
	ES	HSC and erythroid	Interleukin-6 Absence of LIF and cell feeder layer Culture on collagen substrate Hematopoietic growth factors Semisolid media BMP-4	Antibodies against surface markers FACS Immunophenotyping	Wiles and Keller, 1991 Johansson and Wiles, 1995 Perkins et al., 1998
	ES	Keratinocyte (skin)	β-mercaptoethanol Implantation of ES cells in mice	Microscopy Immunofluorescence Observation of skin tissue differentiation Measurement of keratin	Bagutti et al., 1996
	ES	Lymphoid precursor Lymphocyte	Culture of ES in low oxygen concentration (5%) without hematopoietic growth factors	Antibodies to lymphoid cell-surface proteins Analysis of antibody production and lymphocyte receptors	Potocnik et al., 1994
	ES	Macrophage	Interleukin-3 and macrophage colony stimulating factor	Immunophenotyping Immune-function assays	Lieschke and Dunn, 1995
	ES	Mast	Lethal mutations in ES cells Culture of EBs in media containing interleukin-3, stem cell factor	Transplantation of cells into mast cell-deficient mice Immunologic- and inflammation-function tests Analysis of gene expression	Johansson and Wiles, 1995 Tsai et al., 2000
	ES	Melanocyte	Dexamethasone Stromal cell layer Steel factor	Morphology studies Reactivity to growth factors Expression of melanogenic markers	Yamane et al., 1999
	ES	Neuron	Expression of noggin cDNA in ES Expression of neuronal determination gene EB exposed to retinoic acid	Detection of antibodies to neuronal proteins	O'Shea, 1999
	ES	Oligodendrocyte	Retinoic acid Induced spinal cord injury Transplantation of ES-derived cells into spinal cord of mice	Detection of remyelination in spinal cord Antibodies to oligodendrocyte-specific proteins	Liu et al., 2000
	ES	Osteoblast (bone cell)	Co-cultured with fetal mouse osteoblasts Dexamethasone, retinoic acid, ascorbic acid, β-glycerophosphate	Microscopy; observation of mineralized bone nodules Histochemistry	Buttery et al., 2001
	ES	Pancreatic	Insertion of insulin-gene promoter into ES	Antibodies to cellular proteins Measurement of insulin, glucagon, somatostatin Observation of islet-like organization of cells Transplantation of cells into diabetic mice with resultant lowering of blood glucose	Soria et al., 2000
	ES	Pancreatic islet-like	Serum-free media Absence of feeder-cell layer Basic fibroblast growth factor Nicotinamide	Detection of antibodies to cellular and cell-surface proteins	Lumelsky et al., 2001
	ES	Skeletal muscle	Overexpression of insulin-like growth factor-2 in ES through gene insertion Dimethyl sulfoxide	Observation of myocyte differentiation Measurement of myocyte-specific gene expression and proteins	Prelle et al., 2000
	ES	Skeletal muscle	Transforming growth factor-beta and retinoic acid ES co-culture with stromal cells Fetal calf serum β-mercaptoethanol	Observation of myocyte differentiation Detection of functional muscle cell receptors Measurement of myocyte-specific gene expression	Slager et al., 1993 Rohwedel et al., 1994
	ES	Smooth muscle	Retinoic acid and db-cAMP Culture over collagen IV matrix Vascular endothelial growth factor Platelet-derived growth factor-BB	Electron microscopy observation of vascular structures Detection of smooth muscle markers: SMA, CGA7	Drab et al., 1997 Yamashita et al., 2000
	ES	Smooth muscle	Platelet-derived growth factor	FACS Detection of smooth muscle cell proteins	Hirashima et al., 1999
	ES	White blood cell	Interleukin-3 Transplantation of ESs into lymphocyte-deficient mice	Measurement of lymphocyte-specific gene expression Radioimmunoassay	Wiles and Keller, 1991
	ES	White blood cell	Transplantation of ES cells into lymphocyte-deficient mice	Histology Immunophenotyping Antibodies to cell-specific proteins	Rathjen et al., 1998
Gonadal ridge (fetal)	Embryonic primordial germ cell	Endoderm Mesoderm Ectoderm	"Reprogramming" primordial germ cells: culture of primordial germ cell with LIF, basic fibroblast growth factor and Steel factor	Histology Immunocytochemistry	Matsui et al., 1992
Liver	HSC	HSC All blood cell lineages	Enrichment of cell populations through immunoselection Purification of CD45⁺ liver cells Selection of cells with HSC markers Transplantation of HSCs into lethally irradiated mice	Colony-forming assays Detection of in vitro growth of hematopoietic colonies by flow cytometry and cell sorting Liver-derived cells reconstituted from bone marrow of transplanted mice FACS	Taniguchi et al., 199
Pancreas	Pancreatic ductal epithelial cell	Alpha, beta, and delta pancreatic islet	Stem cells isolated from prediabetic adult, nonobese mice Cells cultured for an extensive period Pancreatic cells transplanted into diabetic mice	Analysis of pancreatic cell gene expression and differentiation markers Glucose challenge test in vitro Observation of reversal of insulin-dependent diabetes in mice with transplants	Ramiya et al., 2000
	Unselected pancreatic cells	Hepatocyte	Pancreatic cells transplanted into mice with liver-enzyme deficiency	Detection of normalized liver function in mice Histological evidence of donor-derived hepatocytes	Wang et al., 2001
Skeletal muscle	Muscle	Adipocyte	Long-chain fatty acids Thiazolidinediones	Assays of adipocyte enzyme function Observation of adipocyte differentiation Detection of adipocyte-specific gene expression	Grimaldi et al., 1997
	Muscle	Osteoclast and osteocyte Osteoprogenitor	Exposure of donor cells to BMP-2 Retroviral transfection of cells with vector and transplantation into severe combined immunodeficient mice (SCID)	Detection of ectopic bone formation Detection of muscle-derived cells Co-localization with osteocalcin-producing cells in newly formed bone matrix	Bosch et al., 2000
	Muscle Satellite	HSC Myocyte precursor	Isolation of transcription factor Pax7 as a gene expressed specifically in satellite cell-derived myoblasts	Detection of Pax7^-/- and Pax7⁺ muscle cells in hematopoietic and myogenic cells	Seale et al., 2000
	Muscle Satellite or SP	All blood cell lineages HSC	Transplant of muscle-derived cells into lethally irradiated mice	Observation of engraftment of muscle cells in bone marrow Antibodies to hematopoietic cell markers FACS	Jackson et al., 1999 Gussoni et al., 1999
	Satellite	Myocyte Myocyte precursor	Induced tissue injury; mechanical and denervation stress Transcription factor expression	Detection of myocyte progenitor and myocyte-specific proteins and mRNA transcripts	Megeney et al., 199
Spinal cord	NSC	Astrocyte Neuron Oligodendrocyte	Basic fibroblast growth factor Epidermal growth factor	Detection of antibodies to neural cell proteins	Weiss et al., 1996

Appendix D.ii. Published Reports on Isolation and Differentiation of Human Fetal Tissue Germ Cells
Origin		Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Tissue	Cell Type	Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Gonadal ridge	Primordial germ cell	Embryoid bodies	SDEC line of embryoid body derived cells transplanted into rats paralyzed with a virus induced motor neuron degeneration	Functional assessment of rat locomotion and righting ability (turning from supine to prone) Histopathologic examination of motor axons Immunohistochemistry of mature neurons: NeuN⁺ and 68-kilodalton neurofilament	Kerr et al., 2001
	Primordial germ cell	Embryoid bodies with neural cells, vascular endothelium, muscle cells, endodermal derivatives	Leukemia inhibitory factor, Basic fibroblast growth factor	Clonal expression, polymerase chain reaction Ethidium bromide fluorescence detection Surface markers: 68-kilodalton neurofilament, neuron-specific enolase, tau, vimentin, human nestin, galactocerebroside, O4, SMI32	Shamblott et al., 2001
	Primordial germ cell	Embryoid bodies with three germ layers: endoderm, mesoderm, ectoderm	Leukemia inhibitory factor, Basic fibroblast growth factor	Detection of surface markers: SSEA-1, SSEA-3, SSEA-4, TRA-1-60, TRA-1- 81	Shamblott et al., 1998

Appendix D.iii. Published Reports on Isolation and Differentiation of Human Embryonic Stem Cells
Origin		Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Tissue	Cell Type	Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Human embryo (from in vitro fertilization (IVF))	Blastocyst inner-cell mass	Ectoderm Endoderm Mesoderm Neuronal progenitor cell	Leukemia inhibitory factor Injection into severe combined immunodeficient (SCID) mice	Developed two lines (HES-1, HES-2) Clonal expression Polymerase chain reaction Surface markers: SSEA-1, SSEA-4, TRA-1–60, GTCM-2	Reubinoff et al., 2000
	Blastocyst inner-cell mass (H9 clone line from Thomson et al., 1998)	Cardiomyocyte	Embryoid body formation (See Itskovitz-Eldor et al., 2000)	Visualization of contracting areas in embryoid bodies Immunohistochemistry for cardiac myosin heavy chain, alpha-actinin, desmin, cardiac troponin I, and antinaturetic protein.	Assady et al., 2001
	Blastocyst inner-cell mass (H9 clone line from Thomson et al., 1998)	Cardiomyocyte	Embryoid body formation	Polymerase chain reaction for cardiac-specific genes and transcription factors	Kehat et al., 2001
	Blastocyst inner-cell mass (H9 clone line from Thomson et al., 1998)	Cardiomyocyte Endoderm Hematopoietic Neuron	Leukemia inhibitory factor Basic fibroblast growth factor Collagenase or trypsin/EDTA to induce embryoid body	Clonal expression Polymerase chain reaction Surface markers: gamma-globin, 68-kilodalton neurofilament, alpha-fetoprotein, albumin	Itskovitz-Eldor et al., 2000
	Blastocyst inner-cell mass (H9 clone line from Thomson et al., 1998)	Ectoderm: brain, skin, adrenal Endoderm: liver, pancreas Mesoderm: muscle, bone, kidney, urogenital, heart, hematopoietic, hematopoietic	Basic fibroblast growth factor, transforming growth factor beta 1, activin-A, bone morphogenic protein 4 hepatocyte growth factor, epidermal growth factor, beta nerve growth factor, retinoic acid	Clonal expression Polymerase chain reaction Surface markers	Schuldiner et al., 2000
	Blastocyst inner-cell mass (H9 clone line from Thomson et al., 1998)	Ectoderm: neural epithelium, embryonic ganglia, stratified squamous epithelium Endoderm: gut epithelium Mesoderm: cartilage, bone, smooth muscle, striated muscle	Injection of cell lines into severe combined immunodeficient mice Leukemia inhibitory factor Type IV collagenase	Surface markers: SSEA-3, SSEA-4, TRA-160, TRA-181, alkaline phosphatase Radioimmunoassay detection: alpha-fetoprotein and human chorionic gonadotropin	Thomson et al., 1998
	Blastocyst inner-cell mass (H9 clone line from Thomson et al.,1998)	Pancreatic beta cell	Embryoid body formation (See Itskovitz-Eldor et al., 2000) No leukemia inhibitory factor or basic fibroblast growth factor	Immunohistochemistry for insulin Polymerase chain reaction for insulin, IPF1/PDX1, Ngn3, betaactin, Glut-1, Glut-2, glucokinase, and Oct 4	Assady et al., 2001

Appendix D.iv. Published Reports on Isolation and Differentiation of Human Embryonic Carcinoma Stem Cells
Origin		Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Tissue	Cell Type	Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Teratocarcinoma	Embryonic carcinoma (EC)	Endodermal progenitor cell	Absence of feeder cell layer Bone morphogenetic protein-2 Retinoic acid	Analysis of stem cell marker-gene transcription Immunochemistry Immunofluorescence	Roach et al., 1994 Pera and Herszfeld, 1998
	EC	Neuron	EC transplanted into mouse brain	Observation of functional synapses Immunochemistry	Trojanowski et al., 1993
	EC	Glial Neuron	Retinoic acid	Measurement of mRNA for GABA(A) receptorchloride complex Recording of whole-cell voltage-clamp measurements in differentiated cells in the presence of GABA(A) receptor antagonists and activators (bicuculline and flurazepam, respectively)	Reynolds et al., 1994
	EC	Glial Neuron	Retinoic acid	Detection of neurons with HNK-1 antibody Measurement of acetylcholine synthesis and detection of high-affinity uptake sites for GABA	McBurney et al., 1988
	EC	Neuron	Retinoic acid	Morphology and histology Analysis of neuron-specific proteins	Andrews, 1984
Teratocarcinoma or teratoma	EC	Tumors containing tissue types from endoderm, mesoderm, and ectoderm	Bone morphogenetic protein-7 EC cells cultured without feeder cell layer Transplantation of EC cells into mice	Morphology, histology, and cell staining Observation of tissue types from endoderm, mesoderm, and ectoderm Observation of extended self-renewal of EC cells Analysis of chromosomes and specific genes Detection of cell-specific proteins Cytochemical assay	Andrews et al., 1984 Thompson et al., 1984 Pera, 1989

Appendix D.v. Published Reports on Isolation and Differentiation of Human Adult Stem Cells
Origin		Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Tissue	Cell Type	Cell Types Developed	Differentiation Conditions	Methods of Characterization	Reference
Blood	Circulatory Skeletal	Adipocyte Osteocyte	Leukemia inhibitory factor (LIF) Transplantation of stem cells into bg-nu-xid immunocompromised mice	Antibody labeling Polymerase chain reaction	Kuznetsov, 2001
Bone marrow	Angioblast (endothelial precursor)	Mature endothelia and newly formed blood vessels	Angioblasts isolated by mobilizing peripheral blood with granulocyte colony stimulating factor Angioblasts injected into rats with experimental myocardial infarction	Observation of neovascularization within myocardium from transplanted cells Detection of improved cardiac function in experimental animals	Kocher et al., 2001
	Hematopoietic stem cell (HSC)	Hepatocyte Cholangiocyte	Bone marrow transplantation	Probed for presence and function of Y chromosome-containing liver cells Measured expression of liver-specific proteins Immunochemistry	Alison et al., 2000 Theise et al., 2000
	Human marrow stromal	Stromal-derived cell engrafted in rat brain	Isolation of marrow stromal cell from human volunteers; injection of stromal cell into rat brain	Observation of engraftment, migration, and survival of stromalderived cell in rat brain Observation of loss of stromal cell functions Antibodies to cell-surface proteins	Azizi et al., 1998
	Mesenchymal stem cell (MSC)	Adipocyte Chondrocyte Osteocyte	Fetal bovine serum, dexamethasone, isobutylxanthine, insulin, ascorbate, indomethacin, transforming growth factor-B3, and glycerol phosphate	Histology and immunofluorescence Detection of lipids and specific enzyme activity of adipocytes and osteocytes Specific staining for chondrocytes	Pittenger et al., 1999
	MSC	Neuron	Prolonged expansion of MSCs as undifferentiated cells β-mercaptoethanol (BME) Butylated hydroxyanisole (BHA)	Histology Detection of numerous neuron-specific proteins via staining and antibody binding	Woodbury et al., 2000
	MSC	Neuron	MSCs cultured with fetal rat brain cells Epidermal growth factor Brain-derived neurotrophic factor	Detection of nestin and nestin-gene expression Detection of neuron-specific proteins	Sanchez-Ramos et al., 2000
	MSC	Adipocyte Bone marrow stromal cell Cardiomyocyte Chondrocyte Myocyte Thymic stromal cell	MSCs isolated from bone marrow Transplantation of MSCs into fetal sheep	Analysis of human gene expression in sheep tissues Confirmed presence of human cells by immunohistochemistry	Liechty et al., 2000
Bone marrow (fetal)	HSC	HSC Red blood cell lineages White blood cell lineages	Enrichment of hematopoietic cell populations by cell selection Transplantation of bone marrow and thymus cells into mice	Establishment of long-term multilineage cultures of hematopoietic colonies Fluorescence-activated cell sorting (FACS) Engraftment of hematopoietic cells in mice	Baum et al., 1992
Brain	Neural stem cell (NSC)	Muscle cell	Exposure of NSCs to myoblasts Dissociation of NSC clusters Transplantation of human NSCs into mice with induced muscle injury	Observation of differentiated skeletal muscle cells from primary and culture-derived NSCs Demonstration of NSC engraftment in mice by detection of expression of specific genes	Galli et al., 2000
Brain (adult and neonatal)	Neural progenitor cell (NPC)	Astrocyte Neuron Oligodendrocyte	NPCs cultured in medium containing glutamine, amphotericin-B, antibiotics, fetal calf serum, basic fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor AB Transplantation of human central nervous system stem cells (hCNS-SCs) into mice	Observation of functional engraftment of NPCs into mouse brain Antibody labeling of neuronal cell-surface proteins	Palmer et al., 2001
Brain (fetal)	Human central nervous system stem cell (hCNS-SC)	Astrocyte Neuron Oligodendrocyte	Fibroblast growth factor-2, epidermal growth factor, lymphocyte inhibitory factor, neural survival factor-1, brain-derived and glial-derived neurotrophic factors	Observation of neurosphere formation and self-renewal of hCNS-SCs Demonstration of engraftment, proliferation, migration, and neural differentiation of hCNS-SCs FACS	Uchida et al., 2000
Fat	Stromal vascular cell fraction of processed lipoaspirate	Adipocyte precursor Osteocyte precursor Chondrocyte precursor Myocyte precursor	Co-cultured with mouse adipocytes, isobutylmethylxanthine, dexamethasone Co-cultured with human osteoblasts, insulin, indomethacin, antibiotic/antimycotic dexamethasone, ascorbate, b-glycerophosphate, antibiotic/antimycotic Co-cultured with human skeletal myocytes, insulin, transforming growth factor-B, ascorbate, antibiotic/antimycotic dexamethasone, hydrocortisone, antibiotic/antimycotic	Staining for lipid accumulation Staining for alkaline phosphatase activity Staining for bone formation Staining for proteoglycan-rich matrix Antibody binding to collagen II Visualization of multinucleation Staining for muscle protein: myosin Antibody binding to MyoD1	Zuk et al., 2001
Liver (fetal)	HSC	Hematopoietic progenitor cell (HPC) Red blood cell lineages White blood cell lineages	Co-culture of HSCs with mouse stromal cells Implantation of fetal hematopoietic liver cells into immunocompromised mice	Demonstration of differentiation into red and white blood cell lineages through colony-forming assays and detection of surface markers characteristic of the hematopoietic system	McCune et al., 1988 Namikawa et al., 1990
Pancreas	Nestin-positive islet-derived progenitor cell (NIP)	Pancreatic Hepatic	NIPs obtained from pancreatic islets and cultured for extended periods	Observation of extended proliferative, self renewing, and multipotent capacity Expression of hepatic and exocrine pancreatic markers Demonstration of ductal and endocrine pancreatic features Production of insulin and glucagons	Zulewski et al., 2000
Umbilical cord blood	HPC	Most red and white blood cell lineages	Collection and sorting Stimulation with colony-stimulating factors and interleukin-3	Demonstration of multipotent progenitor, granulocyte-macrophage, and erythroid cell lines	Broxmeyer et al., 1989
	HSC Mesenchymal progenitor cell (MPC)	Most red and white blood cell lineages Osteoblasts Adipocytes	Mixtures of dexamethasone, β-glycerol, ascorbate, insulin, isobutylmethylxanthine, and indomethacin	Cell morphology Cytochemical analysis of osteoblast and adipocyte products Immunophenotyping	Erices et al., 1999

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Appendix C | Table of Contents | Appendix E

Historical content: June 17, 2001

Frequently Asked Questions

Stem Cell Research

Tools

Appendix D: Stem Cell Tables

Compendium of Scientific Publications Regarding the Isolation and Characterization of Stem Cells

Appendix D.vi. References