Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation
Rationale The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Objective Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Methods And Results Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit + CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4+ CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit+ CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. Conclusions MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics. © 2010 American Heart Association, Inc.
Main Authors: | , , , , , , , , , , , , , , , , |
---|---|
Format: | artículo biblioteca |
Language: | English |
Published: |
Lippincott Williams & Wilkins
2010
|
Subjects: | Myocardial Infarction, Mesenchymal Stem Cells, Cardiac Stem Cells, Myocardial Regeneration, |
Online Access: | http://hdl.handle.net/20.500.12792/2050 http://hdl.handle.net/10261/292563 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
dig-inia-es-10261-292563 |
---|---|
record_format |
koha |
spelling |
dig-inia-es-10261-2925632023-02-20T07:30:13Z Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation Hatzistergos, K. E. Quevedo, H. Oskouei, B. N. Hu, Q. Feigenbaum, G. S. Margitich, I. S. Mazhari, R. Boyle, A. J. Zambrano, J. P. Rodriguez, J. E. Dulce, R. Pattany, P. M. Valdes, D. Revilla Calvo, Concepción Heldman, A. W. McNiece, I. Hare, J. M. Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration Rationale The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Objective Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Methods And Results Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit + CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4+ CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit+ CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. Conclusions MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics. © 2010 American Heart Association, Inc. 2023-02-20T07:30:13Z 2023-02-20T07:30:13Z 2010 artículo Circulation Research 107(7): 913-922 (2010) 0009-7330 http://hdl.handle.net/20.500.12792/2050 http://hdl.handle.net/10261/292563 10.1161/CIRCRESAHA.110.222703 en none Lippincott Williams & Wilkins |
institution |
INIA ES |
collection |
DSpace |
country |
España |
countrycode |
ES |
component |
Bibliográfico |
access |
En linea |
databasecode |
dig-inia-es |
tag |
biblioteca |
region |
Europa del Sur |
libraryname |
Biblioteca del INIA España |
language |
English |
topic |
Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration |
spellingShingle |
Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration Hatzistergos, K. E. Quevedo, H. Oskouei, B. N. Hu, Q. Feigenbaum, G. S. Margitich, I. S. Mazhari, R. Boyle, A. J. Zambrano, J. P. Rodriguez, J. E. Dulce, R. Pattany, P. M. Valdes, D. Revilla Calvo, Concepción Heldman, A. W. McNiece, I. Hare, J. M. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
description |
Rationale The regenerative potential of the heart is insufficient to fully restore functioning myocardium after injury, motivating the quest for a cell-based replacement strategy. Bone marrow-derived mesenchymal stem cells (MSCs) have the capacity for cardiac repair that appears to exceed their capacity for differentiation into cardiac myocytes. Objective Here, we test the hypothesis that bone marrow derived MSCs stimulate the proliferation and differentiation of endogenous cardiac stem cells (CSCs) as part of their regenerative repertoire. Methods And Results Female Yorkshire pigs (n=31) underwent experimental myocardial infarction (MI), and 3 days later, received transendocardial injections of allogeneic male bone marrow-derived MSCs, MSC concentrated conditioned medium (CCM), or placebo (Plasmalyte). A no-injection control group was also studied. MSCs engrafted and differentiated into cardiomyocytes and vascular structures. In addition, endogenous c-kit + CSCs increased 20-fold in MSC-treated animals versus controls (P<0.001), there was a 6-fold increase in GATA-4+ CSCs in MSC versus control (P<0.001), and mitotic myocytes increased 4-fold (P=0.005). Porcine endomyocardial biopsies were harvested and plated as organotypic cultures in the presence or absence of MSC feeder layers. In vitro, MSCs stimulated c-kit+ CSCs proliferation into enriched populations of adult cardioblasts that expressed Nkx2-5 and troponin I. Conclusions MSCs stimulate host CSCs, a new mechanism of action underlying successful cell-based therapeutics. © 2010 American Heart Association, Inc. |
format |
artículo |
topic_facet |
Myocardial Infarction Mesenchymal Stem Cells Cardiac Stem Cells Myocardial Regeneration |
author |
Hatzistergos, K. E. Quevedo, H. Oskouei, B. N. Hu, Q. Feigenbaum, G. S. Margitich, I. S. Mazhari, R. Boyle, A. J. Zambrano, J. P. Rodriguez, J. E. Dulce, R. Pattany, P. M. Valdes, D. Revilla Calvo, Concepción Heldman, A. W. McNiece, I. Hare, J. M. |
author_facet |
Hatzistergos, K. E. Quevedo, H. Oskouei, B. N. Hu, Q. Feigenbaum, G. S. Margitich, I. S. Mazhari, R. Boyle, A. J. Zambrano, J. P. Rodriguez, J. E. Dulce, R. Pattany, P. M. Valdes, D. Revilla Calvo, Concepción Heldman, A. W. McNiece, I. Hare, J. M. |
author_sort |
Hatzistergos, K. E. |
title |
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
title_short |
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
title_full |
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
title_fullStr |
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
title_full_unstemmed |
Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
title_sort |
bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation |
publisher |
Lippincott Williams & Wilkins |
publishDate |
2010 |
url |
http://hdl.handle.net/20.500.12792/2050 http://hdl.handle.net/10261/292563 |
work_keys_str_mv |
AT hatzistergoske bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT quevedoh bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT oskoueibn bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT huq bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT feigenbaumgs bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT margitichis bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT mazharir bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT boyleaj bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT zambranojp bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT rodriguezje bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT dulcer bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT pattanypm bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT valdesd bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT revillacalvoconcepcion bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT heldmanaw bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT mcniecei bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation AT harejm bonemarrowmesenchymalstemcellsstimulatecardiacstemcellproliferationanddifferentiation |
_version_ |
1767603362254028800 |