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:5 January 2012
Reviewer: Claus Kordes
Reviewer's report:
Major Compulsory Revision:
Headline, Results and Discussion: The authors described their isolated UCMSC
as a novel MSC population of the umbilical cord. It is known that MSC can
express CD105 (endoglin), CD73 and CD166. Therefore, the reason for
establishing a new MSC population is not clear. The intensity of gene expression
can also indicate the activation/migration status of the cells rather than a new
population of MSC.
Background, paragraph 5; Discussion: ”So far, the possibility of using human
UCMSC to repair acute liver damage has not been evaluated.” One study that
already dealt with this question was cited by the authors (Tsai et al. 2009;
reference 38) in another context. Indeed, former studies relied on transplanted
hematopoietic stem cells from human umbilical cord blood to evaluate beneficial
effects on liver regeneration (e.g. Sharma et al. 2005). However, the present
study of Patrizia Burra and colleagues is of importance, since evidence for a
differentiation of transplanted human UCMSC into hepatocytes and their
modulatory effects on liver regeneration was provided. Although few studies
about a contribution of transplanted MSC to liver fibrosis without differentiation
into hepatocytes exist (e.g. Baertschiger et al. 2009), the present manuscript is in
line with several recent studies that described beneficial effects of transplanted
bone marrow-derived MSC on liver fibrosis.
Results, page 16, last paragraph, Figure 6: Which TGF-beta variant (TGF-beta1,
2 or 3) was analyzed by the authors?
Results, Page 17: “TGF-beta modulation was correlated with
activation/deactivation of stellate cells.” The data provided by the authors are not
sufficient to demonstrate the activation status of hepatic stellate cells. The
expression of alpha-SMA is not restricted to activated stellate cells, but is also
detectable in portal myofibroblasts. Since both cell types are suggested to be
involved in liver fibrogenesis, the sole detection of alpha-SMA is not sufficient to
evaluate the stellate cell activation. The combined detection of nestin and desmin
is more useful to identify activated stellate cells. Moreover, stellate cells possess
characteristics of stem/progenitor cells (Kordes et al. 2009) and the human
hepatic stellate cell line LX-2 exhibits characteristics of bone marrow
mesenchymal stem cells (Castilho-Fernandes et al. 2011). According to these
findings the alpha-SMA-expressing cells in the present study should be better
described as liver myofibroblasts.
Minor Essential Revision:
Results, page 12, last paragraph: “UCMSC constitutively expressed hepatic
markers.” This was not clearly shown by the authors.
Results, page 13 and Discussion, page 18: The background expression of AFP
and MTP in human UCMSC was not demonstrated by the authors. It is better to
show an agarose gel (including no template control) to demonstrate a basal
expression of these genes.
Figure 1 and Table 3 display variable rates of CD166-positive UCMSC. What is
the reason?
Figure 2 and Figure 3: The typical morphology of hepatocytes was mentioned by
the authors, but not shown in these figures.
Discussion, page 18: A readily accessible autologous source of MSC in adults is
adipose tissue. This should be mentioned by the authors.
Discretionary Revision:
Results, Discussion, page 19: The human UCMSC seem to preserve their
quiescent state on hLAM. Their quiescent state could be indicated by a
decreased expression of nestin.
Minor Issues Not for Publication:
Abstract: “…adult mesenchymal stem cells…” Although mesenchymal stem cells
are adult stem cells it is probably better to omit the term adult in this sentence,
since the MSC were obtained from foetal tissues.
Background, Page 6: “…[is] has been…”
Figure 1: An explanation of the abbreviation DLA-DR was not provided by the
authors. Some readers might be more familiar with the term major
histocompatibility complex (MHC) class II.
Discussion, page 20: “…rather [then] than…”
Legend of Figure 2: “…on petri dishes displayed…”
The key words are missing.
The section Methods should be placed after the section Conclusion in this
journal.
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:5 January 2012
Reviewer: Claus Kordes
Reviewer's report:
Major Compulsory Revision:
Headline, Results and Discussion: The authors described their isolated UCMSC
as a novel MSC population of the umbilical cord. It is known that MSC can
express CD105 (endoglin), CD73 and CD166. Therefore, the reason for
establishing a new MSC population is not clear. The intensity of gene expression
can also indicate the activation/migration status of the cells rather than a new
population of MSC.
Background, paragraph 5; Discussion: ”So far, the possibility of using human
UCMSC to repair acute liver damage has not been evaluated.” One study that
already dealt with this question was cited by the authors (Tsai et al. 2009;
reference 38) in another context. Indeed, former studies relied on transplanted
hematopoietic stem cells from human umbilical cord blood to evaluate beneficial
effects on liver regeneration (e.g. Sharma et al. 2005). However, the present
study of Patrizia Burra and colleagues is of importance, since evidence for a
differentiation of transplanted human UCMSC into hepatocytes and their
modulatory effects on liver regeneration was provided. Although few studies
about a contribution of transplanted MSC to liver fibrosis without differentiation
into hepatocytes exist (e.g. Baertschiger et al. 2009), the present manuscript is in
line with several recent studies that described beneficial effects of transplanted
bone marrow-derived MSC on liver fibrosis.
Results, page 16, last paragraph, Figure 6: Which TGF-beta variant (TGF-beta1,
2 or 3) was analyzed by the authors?
Results, Page 17: “TGF-beta modulation was correlated with
activation/deactivation of stellate cells.” The data provided by the authors are not
sufficient to demonstrate the activation status of hepatic stellate cells. The
expression of alpha-SMA is not restricted to activated stellate cells, but is also
detectable in portal myofibroblasts. Since both cell types are suggested to be
involved in liver fibrogenesis, the sole detection of alpha-SMA is not sufficient to
evaluate the stellate cell activation. The combined detection of nestin and desmin
is more useful to identify activated stellate cells. Moreover, stellate cells possess
characteristics of stem/progenitor cells (Kordes et al. 2009) and the human
hepatic stellate cell line LX-2 exhibits characteristics of bone marrow
mesenchymal stem cells (Castilho-Fernandes et al. 2011). According to these
findings the alpha-SMA-expressing cells in the present study should be better
described as liver myofibroblasts.
Minor Essential Revision:
Results, page 12, last paragraph: “UCMSC constitutively expressed hepatic
markers.” This was not clearly shown by the authors.
Results, page 13 and Discussion, page 18: The background expression of AFP
and MTP in human UCMSC was not demonstrated by the authors. It is better to
show an agarose gel (including no template control) to demonstrate a basal
expression of these genes.
Figure 1 and Table 3 display variable rates of CD166-positive UCMSC. What is
the reason?
Figure 2 and Figure 3: The typical morphology of hepatocytes was mentioned by
the authors, but not shown in these figures.
Discussion, page 18: A readily accessible autologous source of MSC in adults is
adipose tissue. This should be mentioned by the authors.
Discretionary Revision:
Results, Discussion, page 19: The human UCMSC seem to preserve their
quiescent state on hLAM. Their quiescent state could be indicated by a
decreased expression of nestin.
Minor Issues Not for Publication:
Abstract: “…adult mesenchymal stem cells…” Although mesenchymal stem cells
are adult stem cells it is probably better to omit the term adult in this sentence,
since the MSC were obtained from foetal tissues.
Background, Page 6: “…[is] has been…”
Figure 1: An explanation of the abbreviation DLA-DR was not provided by the
authors. Some readers might be more familiar with the term major
histocompatibility complex (MHC) class II.
Discussion, page 20: “…rather [then] than…”
Legend of Figure 2: “…on petri dishes displayed…”
The key words are missing.
The section Methods should be placed after the section Conclusion in this
journal.
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:5 January 2012
Reviewer: Claus Kordes
Reviewer's report:
Major Compulsory Revision:
Headline, Results and Discussion: The authors described their isolated UCMSC
as a novel MSC population of the umbilical cord. It is known that MSC can
express CD105 (endoglin), CD73 and CD166. Therefore, the reason for
establishing a new MSC population is not clear. The intensity of gene expression
can also indicate the activation/migration status of the cells rather than a new
population of MSC.
Background, paragraph 5; Discussion: ”So far, the possibility of using human
UCMSC to repair acute liver damage has not been evaluated.” One study that
already dealt with this question was cited by the authors (Tsai et al. 2009;
reference 38) in another context. Indeed, former studies relied on transplanted
hematopoietic stem cells from human umbilical cord blood to evaluate beneficial
effects on liver regeneration (e.g. Sharma et al. 2005). However, the present
study of Patrizia Burra and colleagues is of importance, since evidence for a
differentiation of transplanted human UCMSC into hepatocytes and their
modulatory effects on liver regeneration was provided. Although few studies
about a contribution of transplanted MSC to liver fibrosis without differentiation
into hepatocytes exist (e.g. Baertschiger et al. 2009), the present manuscript is in
line with several recent studies that described beneficial effects of transplanted
bone marrow-derived MSC on liver fibrosis.
Results, page 16, last paragraph, Figure 6: Which TGF-beta variant (TGF-beta1,
2 or 3) was analyzed by the authors?
Results, Page 17: “TGF-beta modulation was correlated with
activation/deactivation of stellate cells.” The data provided by the authors are not
sufficient to demonstrate the activation status of hepatic stellate cells. The
expression of alpha-SMA is not restricted to activated stellate cells, but is also
detectable in portal myofibroblasts. Since both cell types are suggested to be
involved in liver fibrogenesis, the sole detection of alpha-SMA is not sufficient to
evaluate the stellate cell activation. The combined detection of nestin and desmin
is more useful to identify activated stellate cells. Moreover, stellate cells possess
characteristics of stem/progenitor cells (Kordes et al. 2009) and the human
hepatic stellate cell line LX-2 exhibits characteristics of bone marrow
mesenchymal stem cells (Castilho-Fernandes et al. 2011). According to these
findings the alpha-SMA-expressing cells in the present study should be better
described as liver myofibroblasts.
Minor Essential Revision:
Results, page 12, last paragraph: “UCMSC constitutively expressed hepatic
markers.” This was not clearly shown by the authors.
Results, page 13 and Discussion, page 18: The background expression of AFP
and MTP in human UCMSC was not demonstrated by the authors. It is better to
show an agarose gel (including no template control) to demonstrate a basal
expression of these genes.
Figure 1 and Table 3 display variable rates of CD166-positive UCMSC. What is
the reason?
Figure 2 and Figure 3: The typical morphology of hepatocytes was mentioned by
the authors, but not shown in these figures.
Discussion, page 18: A readily accessible autologous source of MSC in adults is
adipose tissue. This should be mentioned by the authors.
Discretionary Revision:
Results, Discussion, page 19: The human UCMSC seem to preserve their
quiescent state on hLAM. Their quiescent state could be indicated by a
decreased expression of nestin.
Minor Issues Not for Publication:
Abstract: “…adult mesenchymal stem cells…” Although mesenchymal stem cells
are adult stem cells it is probably better to omit the term adult in this sentence,
since the MSC were obtained from foetal tissues.
Background, Page 6: “…[is] has been…”
Figure 1: An explanation of the abbreviation DLA-DR was not provided by the
authors. Some readers might be more familiar with the term major
histocompatibility complex (MHC) class II.
Discussion, page 20: “…rather [then] than…”
Legend of Figure 2: “…on petri dishes displayed…”
The key words are missing.
The section Methods should be placed after the section Conclusion in this
journal.
assistant