Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation

Konstantinos E. Hatzistergos; Henry Quevedo; Behzad N. Oskouei; Qinghua Hu; Gary S. Feigenbaum; Irene S. Margitich; Ramesh Mazhari; Andrew J. Boyle; Juan P. Zambrano; Jose E. Rodriguez; Raul Dulce; Pradip M. Pattany; David Valdes; Concepcion Revilla; Alan W. Heldman; Ian McNiece; Joshua M. Hare

doi:10.1161/CIRCRESAHA.110.222703

Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation

Konstantinos E. Hatzistergos, Henry Quevedo, Behzad N. Oskouei, Qinghua Hu, Gary S. Feigenbaum, Irene S. Margitich, Ramesh Mazhari, Andrew J. Boyle, Juan P. Zambrano, Jose E. Rodriguez, Raul Dulce, Pradip M. Pattany, David Valdes, Concepcion Revilla, Alan W. Heldman, Ian McNiece, Joshua M. Hare

Research output: Contribution to journal › Article › peer-review

550 Scopus citations

Abstract

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+ CSCs in MSC versus control (P+ 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.

Original language	English (US)
Pages (from-to)	913-922
Number of pages	10
Journal	Circulation Research
Volume	107
Issue number	7
DOIs	https://doi.org/10.1161/CIRCRESAHA.110.222703
State	Published - Oct 1 2010
Externally published	Yes

Keywords

cardiac stem cells
mesenchymal stem cells
myocardial infarction
myocardial regeneration

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine
General Medicine

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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, C., Heldman, A. W., McNiece, I., & Hare, J. M. (2010). Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circulation Research, 107(7), 913-922. https://doi.org/10.1161/CIRCRESAHA.110.222703

Hatzistergos, KE, Quevedo, H, Oskouei, BN, Hu, Q, Feigenbaum, GS, Margitich, IS, Mazhari, R, Boyle, AJ, Zambrano, JP, Rodriguez, JE, Dulce, R, Pattany, PM, Valdes, D, Revilla, C, Heldman, AW, McNiece, I & Hare, JM 2010, 'Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation', Circulation Research, vol. 107, no. 7, pp. 913-922. https://doi.org/10.1161/CIRCRESAHA.110.222703

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abstract = "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+ CSCs in MSC versus control (P+ 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.",

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AU - Oskouei, Behzad N.

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AU - Feigenbaum, Gary S.

AU - Margitich, Irene S.

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AU - Boyle, Andrew J.

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AU - Rodriguez, Jose E.

AU - Dulce, Raul

AU - Pattany, Pradip M.

AU - Valdes, David

AU - Revilla, Concepcion

AU - Heldman, Alan W.

AU - McNiece, Ian

AU - Hare, Joshua M.

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N2 - 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+ CSCs in MSC versus control (P+ 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.

AB - 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+ CSCs in MSC versus control (P+ 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.

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Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation

Abstract

Keywords

ASJC Scopus subject areas

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