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TAMARA JORQUIERA
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T A M A R A J O R Q U I E R A
7
Describa y grafique brevemente el estudio
ldquoCell differentiation Hepatocytes from non-hepatic adult
stem cellsrdquo Malcolm R Alison Richard Poulsom
Rosemary Jeffery Amar P Dhillon Alberto Quaglia Joe
Jacob Marco Novelli Grant Prentice Jill Williamson
and Nicholas A Wright Nature 406 257 (20 July
2000) doi10103835018642
T A M A R A J O R Q U I E R A
ABSTRACT
Stem cells are undifferentiated long-lived cells that are capable of many rounds of
division Here we show that adult human liver cells can be derived from stem
cells originating in the bone marrow or circulating outside the liver raising the
possibility that blood-system stem cells could be used clinically to generate
hepatocytes for replacing damaged tissue
T A M A R A J O R Q U I E R A
Evidencia en
seres humanos
Hepatocito
Receptor
XY
XX
Donante
XY
Receptor
XX
Theise ND et al Hepatology 2000
Alison MR et al Nature 2000
Trasplantes de MO
CEacuteLULAS MADRE
T A M A R A J O R Q U I E R A
8
Describa y grafique brevemente el estudio
ldquoChimerism of the transplanted heartrdquo De
Quaini F Urbanek K Beltrami AP Finato N
Beltrami CA Nadal-Ginard B Kajstura J Leri A
Anversa P N Engl J Med 2002 Jan 3346(1)5-
15
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
7
Describa y grafique brevemente el estudio
ldquoCell differentiation Hepatocytes from non-hepatic adult
stem cellsrdquo Malcolm R Alison Richard Poulsom
Rosemary Jeffery Amar P Dhillon Alberto Quaglia Joe
Jacob Marco Novelli Grant Prentice Jill Williamson
and Nicholas A Wright Nature 406 257 (20 July
2000) doi10103835018642
T A M A R A J O R Q U I E R A
ABSTRACT
Stem cells are undifferentiated long-lived cells that are capable of many rounds of
division Here we show that adult human liver cells can be derived from stem
cells originating in the bone marrow or circulating outside the liver raising the
possibility that blood-system stem cells could be used clinically to generate
hepatocytes for replacing damaged tissue
T A M A R A J O R Q U I E R A
Evidencia en
seres humanos
Hepatocito
Receptor
XY
XX
Donante
XY
Receptor
XX
Theise ND et al Hepatology 2000
Alison MR et al Nature 2000
Trasplantes de MO
CEacuteLULAS MADRE
T A M A R A J O R Q U I E R A
8
Describa y grafique brevemente el estudio
ldquoChimerism of the transplanted heartrdquo De
Quaini F Urbanek K Beltrami AP Finato N
Beltrami CA Nadal-Ginard B Kajstura J Leri A
Anversa P N Engl J Med 2002 Jan 3346(1)5-
15
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
ABSTRACT
Stem cells are undifferentiated long-lived cells that are capable of many rounds of
division Here we show that adult human liver cells can be derived from stem
cells originating in the bone marrow or circulating outside the liver raising the
possibility that blood-system stem cells could be used clinically to generate
hepatocytes for replacing damaged tissue
T A M A R A J O R Q U I E R A
Evidencia en
seres humanos
Hepatocito
Receptor
XY
XX
Donante
XY
Receptor
XX
Theise ND et al Hepatology 2000
Alison MR et al Nature 2000
Trasplantes de MO
CEacuteLULAS MADRE
T A M A R A J O R Q U I E R A
8
Describa y grafique brevemente el estudio
ldquoChimerism of the transplanted heartrdquo De
Quaini F Urbanek K Beltrami AP Finato N
Beltrami CA Nadal-Ginard B Kajstura J Leri A
Anversa P N Engl J Med 2002 Jan 3346(1)5-
15
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
Evidencia en
seres humanos
Hepatocito
Receptor
XY
XX
Donante
XY
Receptor
XX
Theise ND et al Hepatology 2000
Alison MR et al Nature 2000
Trasplantes de MO
CEacuteLULAS MADRE
T A M A R A J O R Q U I E R A
8
Describa y grafique brevemente el estudio
ldquoChimerism of the transplanted heartrdquo De
Quaini F Urbanek K Beltrami AP Finato N
Beltrami CA Nadal-Ginard B Kajstura J Leri A
Anversa P N Engl J Med 2002 Jan 3346(1)5-
15
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
8
Describa y grafique brevemente el estudio
ldquoChimerism of the transplanted heartrdquo De
Quaini F Urbanek K Beltrami AP Finato N
Beltrami CA Nadal-Ginard B Kajstura J Leri A
Anversa P N Engl J Med 2002 Jan 3346(1)5-
15
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
Background
Cases in which a male patient receives a heart from a female donor provide an unusual opportunity to test whether primitive cells translocate from the recipient to the graft and whether cells with the phenotypic characteristics of those of the recipient ultimately reside in the donor heart The Y chromosome can be used to detect migrated undifferentiated cells expressing stem-cell antigens and to discriminate between primitive cells derived from the recipient and those derived from the donor
Full Text of Background
Methods
We examined samples from the atria of the recipient and the atria and ventricles of the graft by fluorescence in situ hybridization to determine whether Y chromosomes were present in eight hearts from female donors implanted into male patients Primitive cells bearing Y chromosomes that expressed c-kit MDR1 and Sca-1 were also investigated
Full Text of Methods
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
Results
Myocytes coronary arterioles and capillaries that had a Y chromosome made up 7 to 10 percent of those in the donor hearts and were highly proliferative As compared with the ventricles of control hearts the ventricles of the transplanted hearts had markedly increased numbers of cells that were positive for c-kit MDR1 or Sca-1 The number of primitive cells was higher in the atria of the hosts and the atria of the donor hearts than in the ventricles of the donor hearts and 12 to 16 percent of these cells contained a Y chromosome Undifferentiated cells were negative for markers of bone marrow origin Progenitor cells expressing MEF2 GATA-4 and nestin (which identify the cells as myocytes) and Flk1 (which identifies the cells as endothelial cells) were identified
Full Text of Results
Conclusions
Our results show a high level of cardiac chimerism caused by the migration of primitive cells from the recipient to the grafted heart Putative stem cells and progenitor cells were identified in control myocardium and in increased numbers in transplanted hearts
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
CEacuteLULAS MADRE
Evidencia en
seres humanos
Trasplantes de oacuterganos soacutelidos
XY
Donante
Laflamme MA et al Circ Res 2002
Quaini F et al N Engl J Med 2002
Minami E et al Circulation 2005
XX
XY
Donante
Receptor
XY
Cardiomiocito
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
9
Describa y grafique brevemente el estudio
ldquoAllogeneic mesenchymal stem cells restore
cardiac function in chronic ischemic
cardiomyopathy via trilineage differentiating
capacityrdquo PNAS 2009 106 (33) 14022-
14027 doi101073pnas0903201106 vol
106 no 33 p 14022ndash27
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
ABSTRACT
The mechanism(s) underlying cardiac reparative effects of bone marrow-derived mesenchymal stem cells (MSC)
remain highly controversial Here we tested the hypothesis that MSCs regenerate chronically infarcted
myocardium through mechanisms comprising long-term engraftment and trilineage differentiation Twelve
weeks after myocardial infarction female swine received catheter-based transendocardial injections of
either placebo (n = 4) or male allogeneic MSCs (200 million n = 6) Animals underwent serial cardiac
magnetic resonance imaging and in vivo cell fate was determined by co-localization of Y-chromosome (Ypos)
cells with markers of cardiac vascular muscle and endothelial lineages MSCs engrafted in infarct and
border zones and differentiated into cardiomyocytes as ascertained by co-localization with GATA-4 Nkx25
and α-sarcomeric actin In addition Ypos MSCs exhibited vascular smooth muscle and endothelial cell
differentiation contributing to large and small vessel formation Infarct size was reduced from 193 plusmn 17
to 139 plusmn 20 (P lt 0001) and ejection fraction (EF) increased from 350 plusmn 17 to 413 plusmn 27 (P lt 005)
in MSC but not placebo pigs over 12 weeks This was accompanied by increases in regional contractility and
myocardial blood flow (MBF) particularly in the infarct border zone Importantly MSC engraftment correlated
with functional recovery in contractility (R = 085 P lt 005) and MBF (R = 076 P lt 001) Together these
findings demonstrate long-term MSC survival engraftment and trilineage differentiation following
transplantation into chronically scarred myocardium MSCs are an adult stem cell with the capacity for
cardiomyogenesis and vasculogenesis which contribute at least in part to their ability to repair chronically
scarred myocardium
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
T A M A R A J O R Q U I E R A
