Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerate the resolution of acute liver injury
Version: 1Date:20 December 2011
Reviewer: Laurent Dollé
Reviewer's report:
The paper deserves to be published entirely as a proof of principal that their
isolated hUCMSCs following systemic administration are able to accelerate the
resolution of an acute liver injury tissue (in that case CCl4 injection), opening the
path for future application in regenerative medicine as a novel cell candidate. The
paper contains some strong points.
Strengths
# This work is particularly well illustrated in characterizing human UCMSC. Flow
cytometry has been used for that purpose and it is a powerful means to search
for cells which are rare in vivo.
# The authors have standardized the isolation procedure to obtain a cell
population with hepatogenic properties. 135 samples have been used and 98%
of them gave rise to cell colonies. This analysis emphasizes how strong their
isolation procedure is. Get an adequate cell population at the start is a primordial
request to go further in vitro and in vivo studies.
# The English is fluent and very good, and the writing invites to read fast. The
story has been nicely built suggesting a well-organized brainstorming for that
work.
However I have some minor essential revisions that I have classified as
weaknesses.
Weaknesses
# Figure 4 is a keystone for the paper and needs to be improved. The scales are
barely visible, even double bars are observed, and the magnification are not
visible even after blow-up the pictures that have been submitted. The necrotic
area should be delimited by the authors on the tissue to be clear for anyone on
the area to look at. The authors have quantified (% have been added in the
paper) the area, so to clarify and be complementary to the IHC (in particular HE
stain) graphics might be useful to show. CD68 and PAS-D have been performed
on CCl4 treated liver, but no pictures are shown when the hUCMSCs have been
transplanted and in control as well. A novel title for that figure is more than
welcome because this is the transplantation part of the paper that would sell the
story or not. It is not exclusively ‘histological analysis’.
# Figure 5 is a subsequent figure needed to improve the statements of the figure
4. The authors have never used tracing/tracking strategies to seek their
transplanted cells in injured liver. Even only 2 different days have been
investigated and nothing in between. Change the title of this figure to make it
clear. Can the authors provide proof that no cell fusion is happening in the case
where hUCMSCs have been transplanted? To get a better overview of the hALB
positivity low magnification showing a broad liver section might been required to
estimate the repartition of the transplanted cells in the liver.
# Figure 7 shows a-SMA staining in CCl4 versus CCl4/transplanted animals.
a-SMA is not a specific marker for Hepatic Stellate cells! Fibroblasts, portal
fibroblast and some mesechymal cells express also a-SMA. The authors should
go for co-staining of desmin with a-SMA. Low magnification should be provided
to estimate the broad repartition of the a-SMA+ cells through the tissue. Portal
vein and central vein should be also shown in respect to the conditions
(CCl4/CCl4+transplanted) and avoid to show one or the other separately.
# To check the possible differentiation toward hepatocyte-like cells from their
UCMSCs, the authors have used a simplest panel of markers (PAS staining, ALB
secretion), which are a kind of restrictive. Few other functions (activity or
secretion) might be complementary to the documented parameters reinforcing
the potential acquisition of hepatocyte-like cells. For example: CYP activity, lipid
metabolism, urea secretion…
# It seems that the simplest support is the most suitable for this aim. However,
the authors did not provide any proof that their DCM they used for that paper has
been correctly performed for such application. In particular, proof that the all
components of the ECM are still present after the DCM procedure, with respect
to their quantity and quality.
Other comments:
Show by blood/serum parameters (bilirubin, AST, ALT) that CCl4 is working and
then show for the same parameters in the condition where hUCMSCs have
transplanted will support well the data presented by the authors.
Check the scales on the images of tissues and the quality of the pictures.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that i have no competing interests
Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerate the resolution of acute liver injury
Version: 1Date:20 December 2011
Reviewer: Laurent Dollé
Reviewer's report:
The paper deserves to be published entirely as a proof of principal that their
isolated hUCMSCs following systemic administration are able to accelerate the
resolution of an acute liver injury tissue (in that case CCl4 injection), opening the
path for future application in regenerative medicine as a novel cell candidate. The
paper contains some strong points.
Strengths
# This work is particularly well illustrated in characterizing human UCMSC. Flow
cytometry has been used for that purpose and it is a powerful means to search
for cells which are rare in vivo.
# The authors have standardized the isolation procedure to obtain a cell
population with hepatogenic properties. 135 samples have been used and 98%
of them gave rise to cell colonies. This analysis emphasizes how strong their
isolation procedure is. Get an adequate cell population at the start is a primordial
request to go further in vitro and in vivo studies.
# The English is fluent and very good, and the writing invites to read fast. The
story has been nicely built suggesting a well-organized brainstorming for that
work.
However I have some minor essential revisions that I have classified as
weaknesses.
Weaknesses
# Figure 4 is a keystone for the paper and needs to be improved. The scales are
barely visible, even double bars are observed, and the magnification are not
visible even after blow-up the pictures that have been submitted. The necrotic
area should be delimited by the authors on the tissue to be clear for anyone on
the area to look at. The authors have quantified (% have been added in the
paper) the area, so to clarify and be complementary to the IHC (in particular HE
stain) graphics might be useful to show. CD68 and PAS-D have been performed
on CCl4 treated liver, but no pictures are shown when the hUCMSCs have been
transplanted and in control as well. A novel title for that figure is more than
welcome because this is the transplantation part of the paper that would sell the
story or not. It is not exclusively ‘histological analysis’.
# Figure 5 is a subsequent figure needed to improve the statements of the figure
4. The authors have never used tracing/tracking strategies to seek their
transplanted cells in injured liver. Even only 2 different days have been
investigated and nothing in between. Change the title of this figure to make it
clear. Can the authors provide proof that no cell fusion is happening in the case
where hUCMSCs have been transplanted? To get a better overview of the hALB
positivity low magnification showing a broad liver section might been required to
estimate the repartition of the transplanted cells in the liver.
# Figure 7 shows a-SMA staining in CCl4 versus CCl4/transplanted animals.
a-SMA is not a specific marker for Hepatic Stellate cells! Fibroblasts, portal
fibroblast and some mesechymal cells express also a-SMA. The authors should
go for co-staining of desmin with a-SMA. Low magnification should be provided
to estimate the broad repartition of the a-SMA+ cells through the tissue. Portal
vein and central vein should be also shown in respect to the conditions
(CCl4/CCl4+transplanted) and avoid to show one or the other separately.
# To check the possible differentiation toward hepatocyte-like cells from their
UCMSCs, the authors have used a simplest panel of markers (PAS staining, ALB
secretion), which are a kind of restrictive. Few other functions (activity or
secretion) might be complementary to the documented parameters reinforcing
the potential acquisition of hepatocyte-like cells. For example: CYP activity, lipid
metabolism, urea secretion…
# It seems that the simplest support is the most suitable for this aim. However,
the authors did not provide any proof that their DCM they used for that paper has
been correctly performed for such application. In particular, proof that the all
components of the ECM are still present after the DCM procedure, with respect
to their quantity and quality.
Other comments:
Show by blood/serum parameters (bilirubin, AST, ALT) that CCl4 is working and
then show for the same parameters in the condition where hUCMSCs have
transplanted will support well the data presented by the authors.
Check the scales on the images of tissues and the quality of the pictures.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that i have no competing interests
Please review this paper.
user
Reviewer's report
Title:Systemic administration of a novel human umbilical cord mesenchymal
stem cells population accelerate the resolution of acute liver injury
Version: 1Date:20 December 2011
Reviewer: Laurent Dollé
Reviewer's report:
The paper deserves to be published entirely as a proof of principal that their
isolated hUCMSCs following systemic administration are able to accelerate the
resolution of an acute liver injury tissue (in that case CCl4 injection), opening the
path for future application in regenerative medicine as a novel cell candidate. The
paper contains some strong points.
Strengths
# This work is particularly well illustrated in characterizing human UCMSC. Flow
cytometry has been used for that purpose and it is a powerful means to search
for cells which are rare in vivo.
# The authors have standardized the isolation procedure to obtain a cell
population with hepatogenic properties. 135 samples have been used and 98%
of them gave rise to cell colonies. This analysis emphasizes how strong their
isolation procedure is. Get an adequate cell population at the start is a primordial
request to go further in vitro and in vivo studies.
# The English is fluent and very good, and the writing invites to read fast. The
story has been nicely built suggesting a well-organized brainstorming for that
work.
However I have some minor essential revisions that I have classified as
weaknesses.
Weaknesses
# Figure 4 is a keystone for the paper and needs to be improved. The scales are
barely visible, even double bars are observed, and the magnification are not
visible even after blow-up the pictures that have been submitted. The necrotic
area should be delimited by the authors on the tissue to be clear for anyone on
the area to look at. The authors have quantified (% have been added in the
paper) the area, so to clarify and be complementary to the IHC (in particular HE
stain) graphics might be useful to show. CD68 and PAS-D have been performed
on CCl4 treated liver, but no pictures are shown when the hUCMSCs have been
transplanted and in control as well. A novel title for that figure is more than
welcome because this is the transplantation part of the paper that would sell the
story or not. It is not exclusively ‘histological analysis’.
# Figure 5 is a subsequent figure needed to improve the statements of the figure
4. The authors have never used tracing/tracking strategies to seek their
transplanted cells in injured liver. Even only 2 different days have been
investigated and nothing in between. Change the title of this figure to make it
clear. Can the authors provide proof that no cell fusion is happening in the case
where hUCMSCs have been transplanted? To get a better overview of the hALB
positivity low magnification showing a broad liver section might been required to
estimate the repartition of the transplanted cells in the liver.
# Figure 7 shows a-SMA staining in CCl4 versus CCl4/transplanted animals.
a-SMA is not a specific marker for Hepatic Stellate cells! Fibroblasts, portal
fibroblast and some mesechymal cells express also a-SMA. The authors should
go for co-staining of desmin with a-SMA. Low magnification should be provided
to estimate the broad repartition of the a-SMA+ cells through the tissue. Portal
vein and central vein should be also shown in respect to the conditions
(CCl4/CCl4+transplanted) and avoid to show one or the other separately.
# To check the possible differentiation toward hepatocyte-like cells from their
UCMSCs, the authors have used a simplest panel of markers (PAS staining, ALB
secretion), which are a kind of restrictive. Few other functions (activity or
secretion) might be complementary to the documented parameters reinforcing
the potential acquisition of hepatocyte-like cells. For example: CYP activity, lipid
metabolism, urea secretion…
# It seems that the simplest support is the most suitable for this aim. However,
the authors did not provide any proof that their DCM they used for that paper has
been correctly performed for such application. In particular, proof that the all
components of the ECM are still present after the DCM procedure, with respect
to their quantity and quality.
Other comments:
Show by blood/serum parameters (bilirubin, AST, ALT) that CCl4 is working and
then show for the same parameters in the condition where hUCMSCs have
transplanted will support well the data presented by the authors.
Check the scales on the images of tissues and the quality of the pictures.
Level of interest: An article of outstanding merit and interest in its field
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
I declare that i have no competing interests
assistant