You are here

Back to top

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
Methods of
Tissue Cell Type
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


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


Spangrude et al., 1991

Morrison et al., 1995


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





Vitamin D3

Bone morphogenetic protein-2 (BMP-2)

Detection of antibody binding to cell-surface proteins


Friedenstein et al., 1976

Pereira et al., 1995

Prockop, 1997

  MSC Astrocyte


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


Epidermal growth factor

Brain-derived neurotrophic factor


Retinoic acid


Cell sorting

Sanchez-Ramos et al., 2000
  MSC Neuron Stromal cells expanded as undifferentiated cells


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



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



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


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



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



Retinoic acid Observation of functional synapses

Measurement of neurotransmitters

Slager, et al., 1993

Gottlieb, et al., 1999

  ES Astrocyte


Retinoic acid

Fetal calf serum (10%)


Antibodies to neural cell-specific proteins


Fraichard et al., 1995
  ES Cardiac muscle

Skeletal muscle

Smooth muscle

Retinoic acid

Dimethyl sulfoxide

Transplantation of muscle cells into mice


Detection of cell-specific proteins


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


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


Granulocyte-macrophage stimulating factor

Immune-function assays


Fairchild et al., 2000
  ES Embryoid bodies (EBs) consisting of structures that contain tissues of the three embryonic germ layers: endoderm, mesoderm, and ectoderm


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


Antibodies against surface markers



Wiles and Keller, 1991

Johansson and Wiles, 1995

Perkins et al., 1998

  ES Keratinocyte (skin) β-mercaptoethanol

Implantation of ES cells in mice



Observation of skin tissue differentiation

Measurement of keratin

Bagutti et al., 1996
  ES Lymphoid precursor


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


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


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


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


Wiles and Keller, 1991
  ES White blood cell Transplantation of ES cells into lymphocyte-deficient mice Histology


Antibodies to cell-specific proteins

Rathjen et al., 1998
Gonadal ridge (fetal) Embryonic primordial germ cell Endoderm



"Reprogramming" primordial germ cells: culture of primordial germ cell with LIF, basic fibroblast growth factor and

Steel factor



Matsui et al., 1992

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


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


Assays of adipocyte enzyme function

Observation of adipocyte differentiation

Detection of adipocyte-specific gene expression

Grimaldi et al., 1997
  Muscle Osteoclast and osteocyte


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



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

Satellite or


All blood cell lineages


Transplant of muscle-derived cells into lethally irradiated mice Observation of engraftment of muscle cells in bone marrow

Antibodies to hematopoietic cell markers


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



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
Methods of
Tissue Cell Type
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
Methods of
Tissue Cell Type
Human embryo (from in vitro fertilization (IVF)) Blastocyst inner-cell mass Ectoderm



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




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
Methods of
Tissue Cell Type
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



Roach et al., 1994

Pera and Herszfeld, 1998

  EC Neuron EC transplanted into mouse brain Observation of functional synapses


Trojanowski et al., 1993
  EC Glial


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


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
Methods of
Tissue Cell Type
Blood Circulatory




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


Bone marrow transplantation Probed for presence and function of Y chromosome-containing liver cells

Measured expression of liver-specific proteins


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



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)


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




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



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



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


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


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

Mesenchymal progenitor cell (MPC)

Most red and white blood cell lineages



Mixtures of dexamethasone, β-glycerol, ascorbate, insulin, isobutylmethylxanthine, and indomethacin Cell morphology

Cytochemical analysis of osteoblast and adipocyte products


Erices et al., 1999

Appendix References

  1. Alison, M.R., Poulsom, R., Jeffery, R., Dhillon, A.P., Quaglia, A., Jacob, J., Novelli, M., Prentice, G., Williamson, J., and Wright, N.A. (2000). Hepatocytes from non-hepatic adult stem cells. Nature. 406, 257.
  2. Andrews, P.W., Damjanov, I., Simon, D., Banting, G.S., Carlin, C., Dracopoli, N.C., and Fogh, J. (1984). Pluripotent embryonal carcinoma clones derived from the human teratocarcinoma cell line Tera-2. Differentiation in vivo and in vitro. Lab. Invest. 50, 147–162.
  3. Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K.L., and Tzukerman, M. (2001). Insulin production by human embryonic stem cells. Diabetes, 50, 06282001.pdf.
  4. Azizi, S.A., Stokes, D., Augelli, B.J., DiGirolamo, C., and Prockop, D.J. (1998). Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats—similarities to astrocyte grafts. Proc. Natl. Acad. Sci. U. S. A. 95, 3908–3913.
  5. Bader, A., Al Dubai, H., and Weitzer, G. (2000). Leukemia inhibitory factor modulates cardiogenesis in embryoid bodies in opposite fashions. Circ. Res. 86, 787–794.
  6. Bagutti, C., Wobus, A.M., Fassler, R., and Watt, F.M. (1996). Differentiation of embryonal stem cells into keratinocytes: comparison of wild-type and β(1) integrin-deficient cells. Dev. Biol. 179, 184–196.
  7. Bain, G., Kitchens, D., Yao, M., Huettner, J.E., and Gottlieb, D.I. (1995). Embryonic stem cells express neuronal properties in vitro. Dev. Biol. 168, 342–357.
  8. Baum, C.M., Weissman, I.L., Tsukamoto, A.S., Buckle, A.M., and Peault, B. (1992). Isolation of a candidate human hematopoietic stem-cell population. Proc. Natl. Acad. Sci. U. S. A. 89, 2804–2808.
  9. Bittner, R.E., Schofer, C., Weipoltshammer, K., Ivanova, S., Streubel, B., Hauser, E., Freilinger, M., Hoger, H., Elbe-Burger, A., and Wachtler, F. (1999). Recruitment of bone-marrow-derived cells by skeletal and cardiac muscle in adult dystrophic mdx mice. Anat. Embryol. (Berl) 199, 391–396.
  10. Bjornson, C.R., Rietze, R.L., Reynolds, B.A., Magli, M.C., and Vescovi, A.L. (1999). Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science. 283, 534–537.
  11. Bosch, P., Musgrave, D.S., Lee, J.Y., Cummins, J., Shuler, F., Ghivizzani, S.C., Evans, C., Robbins, P.D., and Huard, J. (2000). Osteoprogenitor cells within skeletal muscle. J. Orthop. Res. 18, 933–944.
  12. Brazelton, T.R., Rossi, F.M., Keshet, G.I., and Blau, H.M. (2000). From marrow to brain: expression of neuronal phenotypes in adult mice. Science. 290, 1775–1779.
  13. Broxmeyer, H.E., Douglas, G.W., Hangoc, G., Cooper, S., Bard, J., English, D., Arny, M., Thomas, L., and Boyse, E.A. (1989). Human umbilical cord blood as a potential source of transplantable hematopoietic stem/progenitor cells. Proc. Natl. Acad. Sci. U. S. A. 86, 3828–3832.
  14. Brustle, O., Jones, K.N., Learish, R.D., Karram, K., Choudhary, K., Wiestler, O.D., Duncan, I.D., and McKay, R.D. (1999). Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science. 285, 754–756.
  15. Buttery, L.D., Bourne, S., Xynos, J.D., Wood, H., Hughes, F.J., Hughes, S.P., Episkopou, V., and Polak, J.M. (2001). Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng. 7, 89–99.
  16. Dani, C., Smith, A.G., Dessolin, S., Leroy, P., Staccini, L., Villageois, P., Darimont, C., and Ailhaud, G. (1997). Differentiation of embryonic stem cells into adipocytes in vitro. J. Cell Sci. 110, 1279–1285.
  17. Dinsmore, J., Ratliff, J., Deacon, T., Pakzaban, P., Jacoby, D., Galpern, W., and Isacson, O. (1996). Embryonic stem cells differentiated in vitro as a novel source of cells for transplantation. Cell Transplant. 5, 131–143.
  18. Doetsch, F., Caille, I., Lim, D.A., Garcia-Verdugo, J.M., and Alvarez-Buylla, A. (1999). Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 97, 703–716.
  19. Doetschman, T., Eistetter, H., Katz, M., Schmit, W., and Kemler, R. (1985). The in vitro development of blastocyst-derived embryonic stem cell lines: formation of visceral yolk sac, blood islands and myocardium. J. Embryol. Exp. Morph. 87, 27–45.
  20. Drab, M., Haller, H., Bychkov, R., Erdmann, B., Lindschau, C., Haase, H., Morano, I., Luft, F.C., and Wobus, A.M. (1997). From totipotent embryonic stem cells to spontaneously contracting smooth muscle cells: a retinoic acid and dbcAMP in vitro differentiation model. FASEB J. 11, 905–915.
  21. Eglitis, M.A. and Mezey, E. (1997). Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc. Natl. Acad. Sci. U. S. A. 94, 4080–4085.
  22. Erices, A., Conget, P., and Minguell, J.J. (1999). Mesenchymal progenitor cells in human umbilical cord blood. Br. J. Haematol. 109, 235–242.
  23. Evans, M.J. and Kaufman, M.H. (1981). Establishment in culture of pluripotential cells from mouse embryos. Nature. 292, 154–156.
  24. Fairchild, P.J., Brook, F.A., Gardner, R.L., Graca, L., Strong, V., Tone, Y., Tone, M., Nolan, K.F., and Waldmann, H. (2000). Directed differentiation of dendritic cells from mouse embryonic stem cells. Curr. Biol. 10, 1515–1518.
  25. Ferrari, G., Cusella-De Angelis, G., Coletta, M., Paolucci, E., Stornaiuolo, A., Cossu, G., and Mavilio, F. (1998). Muscle regeneration by bone marrow-derived myogenic progenitors. Science. 279, 1528–1530.
  26. Fraichard, A., Chassande, O., Bilbaut, G., Dehay, C., Savatier, P., and Samarut, J. (1995). in vitro differentiation of embryonic stem cells into glial cells and functional neurons. J. Cell Sci. 108, 3181–3188.
  27. Friedenstein, A.J., Gorskaja, U.F., and Kulagina, N.N. (1976). Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp. Hematol. 4, 267–274.
  28. Galli, R., Borello, U., Gritti, A., Minasi, M.G., Bjornson, C., Coletta, M., Mora, M., De Angelis, M.G., Fiocco, R., Cossu, G., and Vescovi, A.L. (2000). Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3, 986–991.
  29. Gottlieb, D.I. and Huettner, J.E. (1999). An in vitro pathway from embryonic stem cells to neurons and glia. Cells Tissues Organs. 165, 165–172.
  30. Grimaldi, P.A., Teboul, L., Inadera, H., Gaillard, D., and Amri, E.Z. (1997). Trans-differentiation of myoblasts to adipoblasts: triggering effects of fatty acids and thiazolidinediones. Prostaglandins. Leukot. Essent. Fatty. Acids. 57, 71–75.
  31. Gussoni, E., Soneoka, Y., Strickland, C.D., Buzney, E.A., Khan, M.K., Flint, A.F., Kunkel, L.M., and Mulligan, R.C. (1999). Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature. 401, 390–394.
  32. Hirashima, M., Kataoka, H., Nishikawa, S., Matsuyoshi, N., and Nishikawa, S. (1999). Maturation of embryonic stem cells into endothelial cells in an in vitro model of vasculogenesis. Blood. 93, 1253–1263.
  33. Itskovitz-Eldor, J., Schuldiner, M., Karsenti, D., Eden, A., Yanuka, O., Amit, M., Soreq, H., and Benvenisty, N. (2000). Differentiation of human embryonic stem cells into embryoid bodies comprising the three embryonic germ layers. Mol. Med. 6, 88–95.
  34. Jackson, K.A., Mi, T., and Goodell, M.A. (1999). Hematopoietic potential of stem cells isolated from murine skeletal muscle. Proc. Natl. Acad. Sci. U. S. A. 96, 1448214486.
  35. Jackson, K., Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, and and Goodell MA (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest. 107, 1–8.
  36. Johansson, B.M. and Wiles, M.V. (1995). Evidence for involvement of activin A and bone morphogenetic protein 4 in mammalian mesoderm and hematopoietic development. Mol. Cell Biol. 15, 141–151.
  37. Johansson, C.B., Momma, S., Clarke, D.L., Risling, M., Lendahl, U., and Frisen, J. (1999). Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 96, 25–34.
  38. Kawasaki, H., Mizuseki, K., Nishikawa, S., Kaneko, S., Kuwana, Y., Nakanishi, S., Nishikawa, S.I., and Sasai, Y. (2000). Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron. 28, 31–40.
  39. Kehat, I., Kenyagin-Karsenti, D., Druckmann, M., Segev, H., Amit, M., Gepstein, A., Livne, E., Binah, O., Itskovitz-Eldor, J., and Gepstein, L. (2001). Human embryonic stem cells can differentiate into myocytes portraying cardiomyocytic structural and functional properties. J. Clin. Invest. (in press).
  40. Kerr, D.A., Llado, J., Shamblott, M., Maragakis, N., Irani, D.N., Dike, S., Sappington, A., Gearhart, J., and Rothstein, J. (2001). Human embryonic germ cell derivatives facillitate motor recovery of rats with diffuse motor neuron injury.
  41. Klug, M.G., Soonpaa, M.H., Koh, G.Y., and Field, L.J. (1996). Genetically selected cardiomyocytes from differentiating embryonic stem cells form stable intracardiac grafts. J. Clin. Invest. 98, 216–224.
  42. Kocher, A.A., Schuster, M.D., Szabolcs, M.J., Takuma, S., Burkhoff, D., Wang, J., Homma, S., Edwards, N.M., and Itescu, S. (2001). Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat. Med. 7, 430–436.
  43. Kopen, G.C., Prockop, D.J., and Phinney, D.G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc. Natl. Acad. Sci. U. S. A. 96, 10711–10716.
  44. Kramer, J., Hegert, C., Guan, K., Wobus, A.M., Muller, P.K., and Rohwedel, J. (2000). Embryonic stem cell-derived chondrogenic differentiation in vitro: activation by BMP-2 and BMP-4. Mech. Dev. 92, 193–205.
  45. Krause, D.S., Theise, N.D., Collector, M.I., Henegariu, O., Hwang, S., Gardner, R., Neutzel, S., and Sharkis, S.J. (2001). Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell. 105, 369–377.
  46. Kuznetsov, S.A., Mankani, M.H., Gronthos, S., Satomura, K., Bianco, P., and Robey P.G. (2001). Circulating skeletal stem cells. J. Cell Biol. 153, 1133–40.
  47. Lagasse, E., Connors, H., Al Dhalimy, M., Reitsma, M., Dohse, M., Osborne, L., Wang, X., Finegold, M., Weissman, I.L., and Grompe, M. (2000). Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat. Med. 6, 1229–1234.
  48. Lee, S.H., Lumelsky, N., Studer, L., Auerbach, J.M., and McKay, R.D. (2000). Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat. Biotechnol. 18, 675–679.
  49. Li, M., Pevny, L., Lovell-Badge, R., and Smith, A. (1998). Generation of purified neural precursors from embryonic stem cells by lineage selection. Curr. Biol. 8, 971–974.
  50. Liechty, K.W., MacKenzie, T.C., Shaaban, A.F., Radu, A., Moseley, A.B., Deans, R., Marshak, D.R., and Flake, A.W. (2000). Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat. Med. 6, 1282–1286.
  51. Lieschke, G.J. and Dunn, A.R. (1995). Development of functional macrophages from embryonal stem cells in vitro. Exp. Hematol. 23, 328–334.
  52. Liu, S., Qu, Y., Stewart, T.J., Howard, M.J., Chakrabortty, S., Holekamp, T.F., and McDonald, J.W. (2000). Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc. Natl. Acad. Sci. U. S. A. 97, 6126–6131.
  53. Lumelsky, N., Blondel, O., Laeng, P., Velasco, I., Ravin, R., and McKay, R. (2001). Differentiation of Embryonic Stem Cells to Insulin-Secreting Structures Similiar to Pancreatic Islets. Science. 292, 1389–1394.
  54. Makino, S., Fukuda, K., Miyoshi, S., Konishi, F., Kodama, H., Pan, J., Sano, M., Takahashi, T., Hori, S., Abe, H., Hata, J., Umezawa, A., and Ogawa, S. (1999). Cardiomyocytes can be generated from marrow stromal cells in vitro. J. Clin. Invest. 103, 697–705.
  55. Maltsev, V.A., Rohwedel, J., Hescheler, J., and Wobus, A.M. (1993). Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types. Mech. Dev. 44, 41–50.
  56. Matsui, Y., Zsebo, K., and Hogan, B.L. (1992). Derivation of pluripotential embryonic stem cells from murine primordial germ cells in culture. Cell. 70, 841–847.
  57. McBurney, M.W., Reuhl, K.R., Ally, A.I., Nasipuri, S., Bell, J.C., and Craig, J. (1988). Differentiation and maturation of embryonal carcinoma-derived neurons in cell culture. J. Neurosci. 8, 1063–1073.
  58. McCune, J.M., Namikawa, R., Kaneshima, H., Shultz, L.D., Lieberman, M., and Weissman, I.L. (1988). The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function. Science. 241, 1632–1639.
  59. Megeney, L.A., Kablar, B., Garrett, K., Anderson, J.E., and Rudnicki, M.A. (1996). MyoD is required for myogenic stem cell function in adult skeletal muscle. Genes Dev. 10, 11731183.
  60. Mezey, E., Chandross, K.J., Harta, G., Maki, R.A., and McKercher, S.R. (2000). Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science. 290, 1779–1782.
  61. Morrison, S.J., Uchida, N., and Weissman, I.L. (1995). The biology of hematopoietic stem cells. Annu. Rev. Cell. Dev. Biol. 11, 35–71.
  62. Namikawa, R., Weilbaecher, K.N., Kaneshima, H., Yee, E.J., and McCune, J.M. (1990). Long-term human hematopoiesis in the SCID-hu mouse. J. Exp. Med. 172, 1055–1063.
  63. O'Shea, K.S. (1999). Embryonic stem cell models of development. Anat. Rec. 257, 32–41.
  64. Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S.M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D.M., Leri, A., and Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature. 410, 701–705.
  65. Palmer, T.D., Schwartz, P.H., Taupin, P., Kaspar, B., Stein, S.A., and Gage, F.H. (2001). Progenitor cells from human brain after death. Nature. 411, 42–43.
  66. Pera, M.F., Cooper, S., Mills, J., and Parrington, J.M. (1989). Isolation and characterization of a multipotent clone of human embryonal carcinoma cells. Differentiation. 42, 10–23.
  67. Pera, M.F. and Herszfeld, D. (1998). Differentiation of human pluripotent teratocarcinoma stem cells induced by bone morphogenetic protein-2. Reprod. Fertil. Dev. 10, 551–555.
  68. Pereira, R.F., Halford, K.W., O'Hara, M.D., Leeper, D.B., Sokolov, B.P., Pollard, M.D., Bagasra, O., and Prockop, D.J. (1995). Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage, and lung in irradiated mice. Proc. Natl. Acad. Sci. U. S. A. 92, 4857–4861.
  69. Perkins, A.C. (1998). Enrichment of blood from embryonic stem cells in vitro. Reprod. Fertil. Dev. 10, 563–572.
  70. Petersen, B.E., Bowen, W.C., Patrene, K.D., Mars, W.M., Sullivan, A.K., Murase, N., Boggs, S.S., Greenberger, J.S., and Goff, J.P. (1999). Bone marrow as a potential source of hepatic oval cells. Science. 284, 1168–1170.
  71. Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., and Marshak, D.R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science. 284, 143–147.
  72. Potocnik, A.J., Nielsen, P.J., and Eichmann, K. (1994). in vitro generation of lymphoid precursors from embryonic stem cells. EMBO J. 13, 5274–5283.
  73. Prelle, K., Wobus, A.M., Krebs, O., Blum, W.F., and Wolf, E. (2000). Overexpression of insulin-like growth factor-II in mouse embryonic stem cells promotes myogenic differentiation. Biochem. Biophys. Res. Commun. 277, 631–638.
  74. Prockop, D.J. (1997). Marrow stromal cells as stem cells for nonhematopoietic tissues. Science. 276, 71–74.
  75. Ramiya, V.K., Maraist, M., Arfors, K.E., Schatz, D.A., Peck, A.B., and Cornelius, J.G. (2000). Reversal of insulin-depend-ent diabetes using islets generated in vitro from pancreatic stem cells. Nat. Med. 6, 278–282.
  76. Rathjen, P.D., Lake, J., Whyatt, L.M., Bettess, M.D., and Rathjen, J. (1998). Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy. Reprod. Fertil. Dev. 10, 31–47.
  77. Reubinoff, B.E., Pera, M.F., Fong, C.Y., Trounson, A., and Bongso, A. (2000). Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat. Biotechnol. 18, 399–404.
  78. Reynolds, B.A. and Weiss, S. (1996). Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev. Biol. 175, 1–13.
  79. Reynolds, J.N., Ryan, P.J., Prasad, A., and Paterno, G.D. (1994). Neurons derived from embryonal carcinoma (P19) cells express multiple GABA(A) receptor subunits and fully functional GABA(A) receptors. Neurosci. Lett. 165, 129–132.
  80. Risau, W., Sariola, H., Zerwes, H.G., Sasse, J., Ekblom, P., Kemler, R., and Doetschman, T. (1988). Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies. Development. 102, 471–478.
  81. Roach, S., Schmid, W., and Pera, M.F. (1994). Hepatocytic transcription factor expression in human embryonal carcinoma and yolk sac carcinoma cell lines: expression of HNF-3 in models of early endodermal cell differentiation. Exp. Cell. Res. 215, 189–198.
  82. Rohwedel, J., Maltsev, V., Bober, E., Arnold, H.H., Hescheler, J., and Wobus, A.M. (1994). Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents. Dev. Biol. 164, 87–101.
  83. Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., Freeman, T.B., Saporta, S., Janssen, W., Patel, N., Cooper, D.R., and Sanberg, P.R. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol. 164, 247–256.
  84. Schuldiner, M., Yanuka, O., Itskovitz-Eldor, J., Melton, D., and Benvenisty, N. (2000). Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 97, 11307–11312.
  85. Seale, P., Sabourin, L.A., Girgis-Gabardo, A., Mansouri, A., Gruss, P., and Rudnicki, M.A. (2000). Pax7 is required for the specification of myogenic satellite cells. Cell. 102, 777–786.
  86. Shamblott, M.J., Axelman, J., Littlefield, J.W., Blumenthal, P.D., Huggins, G.R., Cui, Y., Cheng, L., and Gearhart, J.D. (2001). Human embryonic germ cell derivatives express a broad range of develpmentally distinct markers and proliferate extensively in vitro. Proc. Natl. Acad. Sci. U. S. A. 98, 13–118.
  87. Shamblott, M.J., Axelman, J., Wang, S., Bugg, E.M., Littlefield, J.W., Donovan, P.J., Blumenthal, P.D., Huggins, G.R., and Gearhart, J.D. (1998). Derivation of pluripotent stem cells from cultured human primordial germ cells. Proc. Natl. Acad. Sci. U. S. A. 95, 13726–13731.
  88. Slager, H.G., Van Inzen, W., Freund, E., Van den Eijnden-Van Raaij A.J.M., and Mummery, C.L. (1993). Transforming growth factor-beta in the early mouse embryo: implications for the regulation of muscle formation and implantation. Dev. Genet. 14, 212–224.
  89. Soria, B., Roche, E., Berna, G., Leon-Quinto, T., Reig, J.A., and Martin, F. (2000). Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocininduced diabetic mice. Diabetes. 49, 157–162.
  90. Spangrude, G.J., Smith, L., Uchida, N., Ikuta, K., Heimfeld, S., Friedman, J., and Weissman, I.L. (1991). Mouse hematopoietic stem cells. Blood. 78, 1395–1402.
  91. Strubing, C., Ahnert-Hilger, G., Shan, J., Wiedenmann, B., Hescheler, J., and Wobus, A.M. (1995). Differentiation of pluripotent embryonic stem cells into the neuronal lineage in vitro gives rise to mature inhibitory and excitatory neurons. Mech. Dev. 53, 275–287.
  92. Taniguchi, H., Toyoshima, T., Fukao, K., and Nakauchi, H. (1996). Presence of hematopoietic stem cells in the adult liver. Nat. Med. 2, 198–203.
  93. Theise, N.D., Nimmakayalu, M., Gardner, R., Illei, P.B., Morgan, G., Teperman, L., Henegariu, O., and Krause, D.S. (2000). Liver from bone marrow in humans. Hepatology. 32, 11–16.
  94. Thompson, S., Stern, P.L., Webb, M., Walsh, F.S., Engstrom, W., Evans, E.P., Shi, W.K., Hopkins, B., and Graham, C.F. (1984). Cloned human teratoma cells differentiate into neuron-like cells and other cell types in retinoic acid. J. Cell. Sci. 72, 37–64.
  95. Thomson, J.A., Itskovitz-Eldor, J., Shapiro, S.S., Waknitz, M.A., Swiergiel, J.J., Marshall, V.S., and Jones, J.M. (1998). Embryonic stem cell lines derived from human blastocysts. Science. 282, 1145–1147.
  96. Tomita, S., Li, R.K., Weisel, R.D., Mickle, D.A., Kim, E.J., Sakai, T., and Jia, Z.Q. (1999). Autologous transplantation of bone marrow cells improves damaged heart function 672. Circulation. 100 (Suppl. II), 11247–11256.
  97. Trojanowski, J.Q., Mantione, J.R., Lee, J.H., Seid, D.P., You, T., Inge, L.J., and Lee, V.M. (1993). Neurons derived from a human teratocarcinoma cell line establish molecular and structural polarity following transplantation into the rodent brain. Exp. Neurol. 122, 283–294.
  98. Tsai, M., Wedemeyer, J., Ganiatsas, S., Tam, S.Y., Zon, L.I., and Galli, S.J. (2000). In vivo immunological function of mast cells derived from embryonic stem cells: an approach for the rapid analysis of even embryonic lethal mutations in adult mice in vivo. Proc. Natl. Acad. Sci. U. S. A. 97, 9186–9190.
  99. Uchida, N., Buck, D.W., He, D., Reitsma, M.J., Masek, M., Phan, T.V., Tsukamoto, A.S., Gage, F.H., and Weissman, I.L. (2000). Direct isolation of human central nervous system stem cells. Proc. Natl. Acad. Sci. U. S. A. 97, 14720–14725.
  100. Wakitani, S., Saito, T., and Caplan, A.I. (1995). Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine 754. Muscle. Nerve. 18, 1417–1426.
  101. Wang, X., Al-Dhalimy, M., Lagasse, E., Finegold, M., and Grompe, M. (2001). Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells. Am. J. Pathol. 158, 571–579.
  102. Weiss, S., Dunne, C., Hewson, J., Wohl, C., Wheatley, M., Peterson, A.C., and Reynolds, B.A. (1996). Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxis. J. Neurosci. 16, 7599–7609.
  103. Westfall, M.V., Pasyk, K.A., Yule, D.I., Samuelson, L.C., and Metzger, J.M. (1997). Ultrastructure and cell-cell coupling of cardiac myocytes differentiating in embryonic stem cell cultures. Cell. Motil. Cytoskeleton. 36, 43–54.
  104. Wiles, M.V. and Keller, G. (1991). Multiple hematopoietic lineages develop from embryonic stem (ES) cells in culture. Development. 111, 259–267.
  105. Wobus, A.M., Rohwedel, J., Maltsev, V., and Hescheler, J. (1995). Development of cardiomyocytes expressing car-diac-specific genes, action potentials, and ionic channels during embryonic stem cell-derived cardiogenesis. Ann. N. Y. Acad. Sci. 752, 460–469.
  106. Woodbury, D., Schwarz, E.J., Prockop, D.J., and Black, I.B. (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61, 364–370.
  107. Yamane, T., Hayashi, H., Mizoguchi, M., Yamazaki, H., and Kunisada, T. (1999). Derivation of melanocytes from embryonic stem cells in culture. Dev. Dyn. 216, 450–458.
  108. Yamashita, J., Itoh, H., Hirashima, M., Ogawa, M., Nishikawa, S., Yurugi, T., Naito, M., Nakao, K., and Nishikawa, S. (2000). Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature. 408, 92–96.
  109. Zuk, P.A., Zhu, M., Mizuno, H., Huang, J., Futrell, J.W., Katz, A.J., Benhaim, P., Lorenz, H.P., and Hedrick, M.H. (2001). Multilineage cells from human adipose tissue: implications for cell- based therapies. Tissue Eng. 7, 211–228.
  110. Zulewski, H., Abraham, E.J., Gerlach, M.J., Daniel, P.B., Moritz, W., Muller, B., Vallejo, M., Thomas, M.K., and Habener, J.F. (2001). Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes. 50, 521–533.

 Appendix C | Table of Contents | Appendix E 

Historical content: June 17, 2001