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 |
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 |