Derivation of Multipotent Mesenchymal
Precursors from Human Embryonic Stem Cells
Tiziano Barberi1, Lucy M. Willis1, Nicholas D. Socci2, Lorenz Studer1*
1 Laboratory of Stem Cell and Tumor Biology, Division of Neurosurgery and Developmental Biology Program, Sloan-Kettering Institute, New York, New York, United States of
America, 2 Computational Biology Center, Sloan-Kettering Institute, New York, New York, United States of America
Competing Interests: The authors
have declared that no competing
Author Contributions: TB and LS
designed the study. TB and LMW
performed the experiments. TB,
LMW, NDS, and LS analyzed the
data. TB, NDS, and LS contributed
to writing the paper.
Academic Editor: Sally Temple,
Albany Medical College, United
States of America
Citation: Barberi T, Willis LM,
Socci ND, Studer L (2005) Deriva-
tion of multipotent mesenchymal
precursors from human embryonic
stem cells. PLoS Med 2(6): e161.
Received: October 13, 2004
Accepted: April 15, 2005
Published: June 28, 2005
Copyright: ? 2005 Barberi et al.
This is an open-access article dis-
tributed under the terms of the
Creative Commons Attribution
License, which permits unre-
stricted use, distribution, and re-
production in any medium,
provided the original work is
Abbreviations: ES, embryonic
stem; FACS, flow-activated cell
sorting; FBS, fetal bovine serum;
hESC, human embryonic stem cell;
hESMPC, human embryonic stem
cell–derived mesenchymal precur-
sor cell; MSC, mesenchymal stem
*To whom correspondence should
be addressed. E-mail:
A B S T R A C T
Human embryonic stem cells provide access to the earliest stages of human development
and may serve as a source of specialized cells for regenerative medicine. Thus, it becomes
crucial to develop protocols for the directed differentiation of embryonic stem cells into tissue-
Methods and Findings
Here, we present culture conditions for the derivation of unlimited numbers of pure
mesenchymal precursors from human embryonic stem cells and demonstrate multilineage
differentiation into fat, cartilage, bone, and skeletal muscle cells.
Our findings will help to elucidate the mechanism of mesoderm specification during
embryonic stem cell differentiation and provide a platform to efficiently generate specialized
human mesenchymal cell types for future clinical applications.
PLoS Medicine | www.plosmedicine.org June 2005 | Volume 2 | Issue 6 | e161 0554
Open access, freely available online P PL Lo oS S MEDICINE
Embryonic stem (ES) cells are pluripotent cells derived
from the inner cell mass of the blastocyst that can be
maintained in culture for an extended period of time without
losing differentiation potential. The successful isolation of
human ES cells (hESCs) has raised the hope that these cells
may provide a universal tissue source to treat many human
diseases. However, directed differentiation of hESCs into
specific tissue types poses a formidable challenge. Protocols
are currently available for only a few cell types, mostly of
neural identity [1–3], and differentiation into many of the cell
types derived from the paraxial mesoderm has not been
reported, with the exception of a recent study indicating
osteoblastic differentiation . Mesenchymal stem cells
(MSCs) have been isolated from the adult bone marrow ,
adipose tissue , and dermis and other connective tissues .
Harvesting MSCs from any of these sources requires invasive
procedures and the availability of a suitable donor. The
number of MSCs that can be obtained from a single donor is
limited, and the capacity of these cells for long-term
proliferation is rather poor. In contrast, hESCs could provide
an unlimited number of specialized cells. In this study, we
present techniques for the generation and purification of
mesenchymal precursors from hESCs and their directed
differentiation in vitro into various mesenchymal derivatives,
including skeletal myoblasts. Our isolation method for
mesenchymal precursors is the first example, to our knowl-
edge, of efficiently deriving structures of the paraxial
mesoderm from ES cells, and further highlights the potential
of hESCs for basic biology and regenerative medicine.
Cell Culture and FACS
Undifferentiated hESCs, H1 (WA-01, XY, passages 40–65)
and H9 (WA-09, XX, passages 35–45), were cultured on
mitotically inactivated mouse embryonic fibroblasts (Spe-
cialty Media, Phillipsburg, New Jersey, United States) and
maintained under growth conditions and passaging techni-
ques described previously . OP9 cells were maintained in
alpha MEM medium containing 20% fetal bovine serum (FBS)
and 2 mM L-glutamine. Mesenchymal differentiation was
induced by plating 10 3 103to 25 3 103cells/cm2on a
monolayer of OP9 cells in the presence of 20% heat-
inactivated FBS in alpha MEM medium. Flow-activated cell
sorting (FACS) (CD73-PE; PharMingen, San Diego, California,
United States) was performed on a MoFlo (Cytomation, Fort
Collins, Colorado, United States). All human ES cell–derived
mesenchymal precursor cell (hESMPC) lines in this study are
of polyclonal origin. Primary human bone marrow–derived
MSCs and primary human foreskin fibroblasts (both from
Poietics, Cambrex, East Rutherford, New Jersey, United
States) were grown in alpha MEM medium containing 10%
FBS and 2 mM L-glutamine.
hESMPCs are grown to confluence followed by exposure to
1 mM dexamethasone, 10 lg/ml insulin, and 0.5 mM
isobutylxanthine (all from Sigma, St. Louis, Missouri, United
States) in alpha MEM medium containing 10% FBS for 2?4
wk. Data were confirmed in hESMPC-H1.1, -H1.2, -H1.3, and -
H9.1 (hESMPC-H1.4 was not tested).
Differentiation of hESMPCs was induced in pellet culture
 by exposure to 10 ng/ml TGF-b3 (R & D Systems,
Minneapolis, Minnesota, United States) and 200 lM ascorbic
acid (Sigma) in alpha MEM medium containing 10% FBS for
3–4 wk. Data were confirmed in hESMPC-H1.1, -H1.3, and -
H9.1 (hESMPC-H1.2 and -H1.4 were not tested).
hESMPCs were plated at low density (1 3 103to 2.5 3 103
cells/cm2) on tissue-culture-treated dishes in the presence of
10 mM b-glycerol phosphate (Sigma), 0.1 lM dexamethasone,
and 200 lM ascorbic acid in alpha MEM medium containing
10% FBS for 3–4 wk. Data were confirmed in hESMPC-H1.1, -
H1.3, and -H9.1 (hESMPC-H1.2 and -H1.4 were not tested).
Confluent hESMPCs were maintained for 2–3 wk in alpha
MEM medium with 20% heat-inactivated FBS. More rapid
induction was observed in the presence of medium con-
ditioned for 24 h by differentiated C2C12 cells. Coculture of
hESMPCs and C2C12 cells was carried out in alpha MEM with
3% horse serum and 1% FBS . Data were confirmed in
hESMPC-H1.3, -H1.4, and -H9.1 (hESMPC-H1.1 and -H1.2
were not tested).
Immunocytochemistry for all surface markers was per-
formed on live cells. Monoclonal antibodies VCAM, STRO-1,
ICAM-1(CD54), CD105, CD29, and MF20 were from Devel-
opmental Studies Hybridoma Bank (University of Iowa, Iowa
City, Iowa, United States); CD73, CD44, and ALCAM(CD166)
were from BD Biosciences Pharmingen (San Diego, Califor-
nia, United States). All other immunocytochemical analyses
were performed after fixation in 4% paraformaldehyde and
0.15% picric acid, followed by permeabilization in 0.3%
Triton X100. Polyclonal antibodies used were MyoD (Santa
Cruz Biotechnology, Santa Cruz, California, United States)
and nestin (gift from R. McKay); monoclonal antibodies were
vimentin, alpha smooth muscle actin, fast-switch myosin, pan-
cytokeratin (all from Sigma), and human nuclear antigen
(Chemicon, Temecula, California, United States).
Alkaline phosphatase reaction was performed using a
commercially available kit (Kit-86; Sigma) and the mineral
was stained with silver nitrate according to the von Kossa
method. Fat granules were visualized by Oil Red O staining
solution (Sigma). Alcian Blue (Sigma) was used to detect
extracellular matrix proteoglycans in chondrogenic cultures.
RT-PCR analysis. Total RNA was extracted by using the
RNeasy kit and DNase I treatment (Qiagen, Valencia,
California, United States). Total RNA (2 lg each) was reverse
transcribed (SuperScript; Invitrogen, Carlsbad, California,
United States). PCR conditions were optimized and linear
amplification range was determined for each primer by
varying annealing temperature and cycle number. PCR
products were identified by size, and identity was confirmed
by DNA sequencing. Primer sequences, cycle numbers, and
annealing temperatures are provided in Table S1.
Affymetrix analysis. Total RNA (5 lg) from primary MSCs,
from hESMPC-H9.1, hESMPC-H1.2, and three samples of
undifferentiated hESCs (H1; passages 42–46), were processed
PLoS Medicine | www.plosmedicine.orgJune 2005 | Volume 2 | Issue 6 | e161 0555
Human ES Cell–Derived Mesenchymal Precursors
by the Memorial Sloan-Kettering Cancer Center Genomics
Core Facility and hybridized on Affymetrix (Santa Clara,
California, United States) U133A human oligonucleotide
arrays. Data were analyzed using MAS5.0 (Affymetrix)
software. Transcripts selectively expressed in each of the
mesenchymal cell populations (MSC, hESMPC-H9.1, and
hESMPC-H1.2) were defined as those called ‘‘increased’’ by
the MAS5.0 algorithm in each of three comparisons with
independent samples of undifferentiated hESCs. A Venn
diagram was generated to visualize overlap in gene expres-
sion. Further statistical analyses were performed as described
Mesenchymal differentiation of hESCs (lines H1 [WA-01]
and H9 [WA-09])  was induced by plating undifferentiated
hESCs on a monolayer of murine OP9 stromal cells , in
the presence of 20% heat-inactivated FBS in alpha MEM
medium. OP9 cells have been previously shown to induce
blood cell differentiation from mouse ES cells . After 40 d
Figure 1. Isolation and Characterization of hESMPCs
(A) FACS (MoFlo, Cytomation) for the isolation of CD73þ precursors (right) and isotype control (left).
(B) Flow cytometry analysis of the CD73þ hESMPC population for various markers characteristic of MSCs, including CD44, CD73, CD105,
CD166, VCAM, ICAM-1, CD29, and STRO-1.
(C) Immunocytochemistry of hESMPCs for MSC markers (VCAM, STRO-1, CD73, and CD105). The cells also express vimentin and alpha smooth
muscle actin. Scale bar = 50 lm.
(D) Venn diagram presenting the overlap among transcripts selectively expressed in hESMPC-H1.2, hESMPC-H9.1, and primary adult human
PLoS Medicine | www.plosmedicine.org June 2005 | Volume 2 | Issue 6 | e1610556
Human ES Cell–Derived Mesenchymal Precursors
of coculture, cells were harvested and sorted by FACS for
CD73, a surface marker expressed in adult MSCs  (Figure
1A). An average of 5% CD73þ cells was obtained from the
mixed culture of OP9 and differentiated hESC progeny.
CD73þ cells were replated in the absence of stromal feeders
on tissue culture plates and expanded in alpha MEM medium
with 20% FBS for 7–14 d. We next established the membrane
antigen profile of the resulting population of flat spindle-like
cells. The H1- and H9-derived CD73þ cells expressed a
comprehensive set of markers that are considered to define
adult MSCs, including CD105(SH2), STRO-1, VCAM (CD106),
CD29(integrin b1), CD44, ICAM -1(CD54), ALCAM(CD166),
vimentin, and alpha smooth muscle actin (Figure 1B and 1C).
The cells were negative for hematopoietic markers such as
CD34, CD45, and CD14. They were also negative for neuro-
ectodermal, epithelial, and muscle cell markers including
nestin, pancytokeratin, and desmin (data not shown). The
human identity of these presumed mesenchymal cells (termed
hESMPC-H1.1, -H1.2, -H1.3, -H1.4, and -H9.1) was confirmed
for all experiments by immunocytochemistry for human
nuclear antigen to rule out the possibility of contamination
with OP9 cells (Figure S1).
To further characterize hESMPCs, we performed genome-
wide expression analysis using oligonucleotide arrays (Affy-
metrix U133A). The expression profiles of hESMPC-H1.2 and
hESMPC-H9.1 were compared with that of human primary
adult MSCs. Housekeeping genes for each of the mesenchy-
mal cell populations were eliminated by subtracting those
transcripts also expressed in at least one of three independ-
ent samples of undifferentiated hESCs. Based on this analysis,
1,280 transcripts were selectively expressed in hESMPC-H1.2,
932 transcripts in hESMPC-H9.1, and 1,218 transcripts in
primary adult MSCs. A remarkable overlap of 579 transcripts
shared among the three mesenchymal populations was
observed (Figure 1D). Using the genes that were selected in
the initial filter, we performed a statistical analysis on the
expression levels to determine whether the genes were
expressed significantly differently in the two cell types. We
used a Bayesian extension to the standard t-test  to assess
this difference. Of the 579 genes, 412 of them were
significantly different, at a false discovery rate cutoff of
0.05. The relative fold changes were also extremely large in
many of the cases. We also looked at the variance of the
expression levels within the cell types. For the MSCs, 94% had
a coefficient of variation less than 20% for the expression (log
transformed); for the ES-derived cells, 72% had a coefficient
Figure 2. Selective Differentiation of hESMPCs into Various Mesenchymal Derivatives
(A) Adipocytic differentiation in the presence of dexamethasone, insulin, and isobutylxanthine. Adipocytic characterization by Oil Red O
staining and RT-PCR analysis for PPARc.
(B) Chondrocytic differentiation in the presence of TGF-b3 and ascorbic acid. Chondrocytic characterization by Alcian Blue staining and RT-
PCR for aggrecan and collagen II.
(C) Osteogenic differentiation in the presence of b-glycerolphosphate, dexamethasone, and ascorbic acid. Osteocytic characterization by von
Kossa staining and RT-PCR for bone-specific alkaline phosphatase (ALP) and bone sialoprotein (BSP).
(D) Phase-contrast image of hESMPCs and RT-PCR for the ES cell markers Nanog and Oct-4 in hESMPC-H1.1 and -H9.1 compared with
undifferentiated H1 hESCs.
Scale bar = 50 lm for all panels.
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Human ES Cell–Derived Mesenchymal Precursors
of variation less than 20%. Numerous known MSC markers
were included in the list of 412 genes, such as the mesenchymal
stem cell protein DSC54 (13.9-fold increase, p , 0.001), neuropilin
1 (30.4-fold increase, p , 0.001), hepatocyte growth factor (48.1-
fold increase, p , 0.001), forkhead box D1 (14.8-fold increase, p
, 0.001), and notch homolog 2 (2.9-fold increase, p , 0.001) .
Table S2 lists the p-values from the test, the mean and
standard deviation of the expression levels, and the relative
fold change of all 412 genes between the two types.
Known markers of MSCs, such as mesenchymal stem cell
protein DSC54, were all included within the 579 shared
transcripts. These findings support the immunocytochemical
data and suggest that hESMPCs and primary MSCs are highly
MSCs are characterized functionally by their ability to
differentiate into mesenchymal tissues, such as fat, cartilage,
and bone. Therefore, we tested whether hESMPCs have the
same potential (Figure 2).
Adipocytic differentiation of hESMPCs was induced under
conditions described previously for primary adult MSCs .
Appearance of cells harboring fat granules was observed after
10–14 d in culture. After 3 wk of induction, more than 70% of
the cells displayed Oil Red Oþ fat granules, and PPARc, a
marker of adipocytic differentiation, was detected by RT-
PCR. (Figure 2A).
Chondrocytic differentiation was achieved using the pellet
culture system . After 28 d in culture, more than 50% of all
cells exhibited robust staining for Alcian Blue, a marker
specific for extracellular matrix proteoglycans. Chondrocytic
differentiation was confirmed by the gene expression of
collagen II and aggrecan, two components of extracellular
matrix selectively expressed by chondrocytes, using RT-PCR
Osteogenic differentiation was induced in the presence of
b-glycerolphosphate . Osteogenesis was demonstrated by
specific staining for calcium deposition in the matrix (von
Kossa, Figure 2C; or Alizarin Red, Figure S2A) and increased
expression of bone-specific alkaline phosphatase and bone sialopro-
tein at day 28 of treatment (Figures 2C and S2B). At day 28,
Alizarin Red staining was detected in approximately 70% of
all cells. Throughout these studies, human adult MSCs and
foreskin fibroblasts were used as positive and negative
In addition to adipocytic, chondrocytic, and osteogenic
differentiation, reports suggested that adult MSCs can form
skeletal muscle . Although generation of skeletal muscle
cells from adult MSCs remains controversial, we tested
whether hESMPCs exhibit this potential. Under the con-
ditions previously described , hESMPC-H1.1 and -H9.1
did not yield significant numbers of MyoDþ cells after 15–20
d in culture. However, when confluent cells were maintained
in culture in the presence or absence of 5-AzaC without
passage for more than 21 d, expression of specific skeletal
muscle markers such as MyoD and fast-switch myosin was
observed (Figure 3A). More rapid myogenic differentiation
was obtained in the presence of 24-h-conditioned medium
from the murine myoblastic cell line C2C12 previously
induced to form myotubes . Direct coculture of hESMPCs
with C2C12 cells led to the formation of hESMPC-derived
myotubes, as visualized by expression of human nuclear
antigen (Figure 3B), similar to those formed by host C2C12
cells. After 1 wk of coculture, myotubes composed of human
nuclei accounted for more than 10% of the total number of
human cells present, and each human myotube was composed
of up to ten human nuclei. Human cell contribution to
myotubes in coculture was confirmed by expression of human
muscle-specific transcripts such as MyoD, myosin heavy chain IIa,
and myogenin (data not shown). These data demonstrate that
hESMPCs can give rise to mesenchymal derivatives typically
obtained from primary adult MSCs, as well as to cells
expressing markers of skeletal muscle.
One concern for the clinical application of hESC-derived
progeny in regenerative medicine is the risk of teratoma
formation due to the presence of residual undifferentiated ES
cells among the differentiated progeny. We did not detect
markers of undifferentiated hESCs, such as Nanog  or Oct-4
, in any of the hESMPCs by RT-PCR (see Figure 2D) and
immunocytochemistry (data not shown), suggesting the lack
of any undifferentiated ES cells in hESMPC cultures.
However, future in vivo studies are required to rule out the
potential of these cells for teratoma formation.
Previous studies have demonstrated the derivation of
neural cells [1–3], hematopoietic  and endothelial lineages
, and cardiomyocytes  from hESCs. This study presents
the induction of paraxial mesoderm with the generation of
multipotent mesenchymal precursors. We calculate that
under these conditions a single undifferentiated hESC yields
an average of one CD73þ cell at day 40 of differentiation,
suggesting a balance between cell proliferation and cell
selection. There were no obvious differences in marker and
gene-expression profile or in differentiation behavior among
the five hESMPC lines generated. However, some of the lines
(e.g., hESMPC9.1) exhibited a tendency of spontaneous
osteogenic differentiation after long-term propagation. Di-
Figure 3. Myogenic Differentiation of hESMPCs
(A) Immunocytochemistry for MyoD (red) and fast-switch myosin
(green). RT-PCR for MyoD in human skeletal muscle as a positive
control (hSM), and in hESMPC-H9.1 cells differentiated for 10 d in
the presence of C2C12-conditioned medium (hESMPC).
(B) Myotube formation induced at high cell densities in the presence
of C2C12 cells. Myotube characterization by immunocytochemistry
for MF20 against sarcomeric myosin (green) and human nuclear
antigen (hNA, red). Left panel: Control undifferentiated hESCs (H9)
do not fuse with C2C12. Right panel: Under identical culture
conditions, hESMPCs (line 9.1) efficiently fuse with C2C12 cells,
forming myotubes containing human nuclei. RT-PCR for human
specific muscle transcripts myosin heavy chain IIa (MYHC-2) and MyoD
in C2C12 cells, in human skeletal muscle as positive control (huSM),
and in hESMPC-H9.1 cells cocultured with C2C12 cells.
PLoS Medicine | www.plosmedicine.org June 2005 | Volume 2 | Issue 6 | e161 0558
Human ES Cell–Derived Mesenchymal Precursors
rected differentiation of hESCs into somatic stem-cell-like
precursors represents a substantial advancement in harness-
ing the developmental potential of hESCs. The high purity,
unlimited availability, and multipotentiality of hESMPCs will
provide the basis for future therapeutic efforts using these
cells in preclinical animal models of disease. Such in vivo
studies will also be required to properly assess the safety
profile of these cells. Furthermore, our system also offers a
novel platform to study basic mechanisms of mesodermal
induction and differentiation during early human develop-
Figure S1. Human Identity of CD73þ Cells after FACS
All cells as visualized by DAPIþnuclei express human nuclear antigen
(hNA) confirming the absence of any contaminating OP9 cells. Scale
bar = 50 lm.
Found at DOI: 10.1371/journal.pmed.0020161.sg001 (148 KB PDF).
Figure S2. Additional Markers of Bone Differentiation
(A) Alizarin Red staining for calcium deposition in the matrix in
hESMPCs untreated (left panel) or treated in the presence of b-
glycerolphosphate (right panel; compare to Figure 2C).
(B) Increasing alkaline phosphatase reactivity during osteogenic
differentiation of hESMPC-H1.1. Scale bar = 250 lm for main
panels, 50 lm for insets.
Found at DOI: 10.1371/journal.pmed.0020161.sg002 (278 KB PDF).
Table S1. All Primers Used in This Study
Found at DOI: 10.1371/journal.pmed.0020161.st001 (22 KB PDF).
Table S2. List of Shared Genes
List of 421 genes that are shared between primary and hESC-derived
mesenchymal precursors but significantly different from undiffer-
entiated hESCs (see main text for details).
Found at DOI: 10.1371/journal.pmed.0020161.st002 (107 KB XLS).
The Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/
geo) accession number for all raw microarray data used in this study
The Unigene (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=
unigene) accession numbers for the gene products discussed in this
paper are aggrecan (Hs.2159 [http://www.ncbi.nlm.nih.gov/UniGene/
clust.cgi?ORG=Hs&CID=2159]); bone sialoprotein (Hs.518726
=518726]); bone-specific alkaline phosphatase (Hs.75431 [http://
collagen II (Hs.408182 [http://www.ncbi.nlm.nih.gov/UniGene/clust.
cgi?ORG=Hs&CID=408182]); forkhead box D1 (Hs.519385 [http://
hepatocyte growth factor (Hs.396530 [http://www.ncbi.nlm.nih.gov/
UniGene/clust.cgi?ORG=Hs&CID=396530]); mesenchymal stem cell
protein (DSC54, Hs.157461 [http://www.ncbi.nlm.nih.gov/UniGene/
clust.cgi?ORG=Hs&CID=157461]); MyoD (Hs.520119 [http://
myogenin (Hs.2830 [http://www.ncbi.nlm.nih.gov/UniGene/clust.
cgi?ORG=Hs&CID=2830]); myosin heavy chain IIa (Hs.513941
UniGene/clust.cgi?ORG=Hs&CID=329296]) ; neuropilin 1
cgi?ORG=Hs&CID=131704]); notch homolog 2 (Hs.549056 [http://
Oct-4 (Hs.504658 [http://www.ncbi.nlm.nih.gov/UniGene/clust.
cgi?ORG=Hs&CID=504658]); and PPARc (Hs.162646 [http://
We thank R. McKay for nestin antibody; P. Song and the Sloan-
Kettering Genomics and Flow Cytometry Core Facilities for technical
assistance; and R. Stan, V. Tabar, M. Tomishima, Y. Elkabetz, and S.
Desbordes for critical review of the manuscript. This work was
supported in part by the Kinetics Foundation. The funder had no
role in the study design, data analysis, decision to publish, or
manuscript preparation and content.
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PLoS Medicine | www.plosmedicine.orgJune 2005 | Volume 2 | Issue 6 | e161 0559
Human ES Cell–Derived Mesenchymal Precursors
Background The discovery and isolation of human embryonic stem cells
(cells that are capable of renewing themselves and turning into the many
different cell types that make up the human body) has the potential to
revolutionize the treatment of many diseases that require the replace-
ment of abnormal or missing cells. In particular, it would be very valuable
to be able to replace tissues that are derived from one particular tissue
type—mesenchyme—which bone, cartilage, fat and muscle develop
from. However, before such treatments can happen, it will be necessary
to work out exactly how embryonic cells become other cells, and
whether it is possible to make these changes happen in the laboratory.
What Did the Researchers Do? They took two lines of completely
undifferentiated human embryonic stem cells and by culturing them in
the presence of mouse cells stimulated them to turn into mesenchymal
cells. They then treated these cells with compounds to make them
change into specialized bone, cartilage, fat, and muscle cells. They were
able to confirm that these cells were all human (important because the
early part of the experiment is done in the presence of mouse cells) and
also that there was no evidence that the cells became cancerous.
What Do These Findings Mean? It is theoretically possible to produce
lines of bone, cartilage, fat, and muscle cells from human embryonic
stem cells. However, the process will need more refinement before the
cell lines could be used for treatment; ideally, for example, all the
culturing would be done without any mouse cells.
Where Can I Get More Information? The United States National
Institutes of Health has a group of Web pages on stem cells: http://
The International Society for Stem Cell Research has a list of frequently
asked questions about stem cells: http://www.isscr.org/science/faq.htm
PLoS Medicine | www.plosmedicine.org June 2005 | Volume 2 | Issue 6 | e1610560
Human ES Cell–Derived Mesenchymal Precursors