Interdisciplinary Stem Cell Institute At University of Miami Finds Signaling Mechanism Responsible For Increased Efficacy Of Combined Cell Therapy
New Research Reveals How Mesenchymal Stem Cells Stimulate Cardiac Stem Cells To Increase Heart Function Following A Heart Attack
Miami, FL– October 4, 2016 – New research from the Interdisciplinary Stem Cell Institute at the University of Miami (ISCI) has uncovered the signaling mechanisms responsible for the interactions of cell types in combined-cell therapy for cardiac regeneration. The study, Stimulatory Effects of MSCs on cKit+ Cardiac Stem Cells Are Mediated by SDF1/CXCR4 and SCF/cKit Signaling Pathways, reveals the underlying influence for the synergistic effect mesenchymal stem cells (MSCs) have in enhancing the efficacy of cardiac cells to regenerate. The findings show that mesenchymal stem cells exhibit profound, yet distinct effects on cardiac stem cell (CSC) migration, proliferation, and differentiation. Furthermore, MSCs enhance CSCs production via the SCF/cKit and SDF1/CXCR4 pathways.
“Our previous research revealed a combined-cell approach improved cardiac function significantly,” says Dr. Joshua Hare, founding director of the Interdisciplinary Stem Cell Institute at the University of Miami and lead investigator on the study. “It is important for us to understand how the cells interact and the underlying mechanism as we work towards developing more efficacious therapies to regenerate damaged heart muscles. These therapies have the potential to improve quality of life for many cardiac patients suffering from heart failure.”
In preceding studies, Dr. Hare and his team have shown that a combined cell therapy of MSCs and CSCs enhances cardiac function significantly over single-celled therapies. To understand the mechanism that causes the positive interactions of the two cell types in cardiac regeneration, ISCI tested the effect that mesenchymal stem cells had upon cardiac stem cells. The study revealed that SDF1 and SCF secreted by bone marrow-derived MSCs have important effects on CSCs. SDF1 promoted migration of CSCs and enhanced the potential for the cells to generate contractile cardiac cells. The cKit receptor activated by the SCF plays an important role in CSCs ability to multiply. The results of the study showed SCF/cKit and the SDF1/CXCR4 pathways to be the mechanisms by which MSCs activate CSCs to migrate, proliferate, and stimulate repair in the diseased heart.
“Combined-cell therapies have shown significant enhancement of viable tissue, improved contractile performance, and increased formation of new cardiomyocytes, which contribute to heart repair,” says Dr. Hare. “Our new research better informs us as to the underlying factors causing the improvement in cardiac function and offers an opportunity to further develop regenerative therapies for patients with damaged and underperforming hearts.”
These findings have important therapeutic implications for cell-based therapy strategies that employ mixtures of cardiac stem cells and mesenchymal stem cells. The study shows that a biologically important relationship exists between MSCs and CSCs, which involves the SCF/cKit and the SDF1/CXCR4 pathways, and may be harnessed for therapeutically enhancing the degree of cardiac regeneration. The new research from Dr. Hare and the team at ISCI, supports the development of novel cell combination-based therapies for the prevention and treatment of heart disease.
ISCI will be conducting clinical trials to further explore combined-cell therapies in cardiac patients.
For additional information, visit http://isci.med.miami.edu/
About Interdisciplinary Stem Cell Institute
The Interdisciplinary Stem Cell Institute (ISCI), founded in 2008 at the University of Miami Miller School of Medicine, is on the cutting-edge of translating stem cell therapies. ISCI is national a leader in conducting clinical trials using stem cells, and has executed research in conjunction with universities and top scientists around the country. ISCI’s goal is to spearhead cell-based therapies for a host of untreatable diseases. Its focus includes research in basic cell biology, hematology, oncology, cardiology, dermatology, diabetes and endocrinology, neurology, orthopaedics, pediatrics, and ethics and science policy. ISCI’s physician-scientists are dedicated to rapidly applying knowledge of stem cell biology to advance therapies for hard-to-treat diseases in an ethical and rigorous manner. In addition to research, ISCI is a cell manufacturing facility for the Cardiovascular Cell Therapy Research Network (CCTRN), and has supplied cells to allow other researchers to conduct important work.
Miami, FL– October 4, 2016 – New research from the Interdisciplinary Stem Cell Institute at the University of Miami (ISCI) has uncovered the signaling mechanisms responsible for the interactions of cell types in combined-cell therapy for cardiac regeneration. The study, Stimulatory Effects of MSCs on cKit+ Cardiac Stem Cells Are Mediated by SDF1/CXCR4 and SCF/cKit Signaling Pathways, reveals the underlying influence for the synergistic effect mesenchymal stem cells (MSCs) have in enhancing the efficacy of cardiac cells to regenerate. The findings show that mesenchymal stem cells exhibit profound, yet distinct effects on cardiac stem cell (CSC) migration, proliferation, and differentiation. Furthermore, MSCs enhance CSCs production via the SCF/cKit and SDF1/CXCR4 pathways.
“Our previous research revealed a combined-cell approach improved cardiac function significantly,” says Dr. Joshua Hare, founding director of the Interdisciplinary Stem Cell Institute at the University of Miami and lead investigator on the study. “It is important for us to understand how the cells interact and the underlying mechanism as we work towards developing more efficacious therapies to regenerate damaged heart muscles. These therapies have the potential to improve quality of life for many cardiac patients suffering from heart failure.”
In preceding studies, Dr. Hare and his team have shown that a combined cell therapy of MSCs and CSCs enhances cardiac function significantly over single-celled therapies. To understand the mechanism that causes the positive interactions of the two cell types in cardiac regeneration, ISCI tested the effect that mesenchymal stem cells had upon cardiac stem cells. The study revealed that SDF1 and SCF secreted by bone marrow-derived MSCs have important effects on CSCs. SDF1 promoted migration of CSCs and enhanced the potential for the cells to generate contractile cardiac cells. The cKit receptor activated by the SCF plays an important role in CSCs ability to multiply. The results of the study showed SCF/cKit and the SDF1/CXCR4 pathways to be the mechanisms by which MSCs activate CSCs to migrate, proliferate, and stimulate repair in the diseased heart.
“Combined-cell therapies have shown significant enhancement of viable tissue, improved contractile performance, and increased formation of new cardiomyocytes, which contribute to heart repair,” says Dr. Hare. “Our new research better informs us as to the underlying factors causing the improvement in cardiac function and offers an opportunity to further develop regenerative therapies for patients with damaged and underperforming hearts.”
These findings have important therapeutic implications for cell-based therapy strategies that employ mixtures of cardiac stem cells and mesenchymal stem cells. The study shows that a biologically important relationship exists between MSCs and CSCs, which involves the SCF/cKit and the SDF1/CXCR4 pathways, and may be harnessed for therapeutically enhancing the degree of cardiac regeneration. The new research from Dr. Hare and the team at ISCI, supports the development of novel cell combination-based therapies for the prevention and treatment of heart disease.
ISCI will be conducting clinical trials to further explore combined-cell therapies in cardiac patients.
For additional information, visit http://isci.med.miami.edu/
About Interdisciplinary Stem Cell Institute
The Interdisciplinary Stem Cell Institute (ISCI), founded in 2008 at the University of Miami Miller School of Medicine, is on the cutting-edge of translating stem cell therapies. ISCI is national a leader in conducting clinical trials using stem cells, and has executed research in conjunction with universities and top scientists around the country. ISCI’s goal is to spearhead cell-based therapies for a host of untreatable diseases. Its focus includes research in basic cell biology, hematology, oncology, cardiology, dermatology, diabetes and endocrinology, neurology, orthopaedics, pediatrics, and ethics and science policy. ISCI’s physician-scientists are dedicated to rapidly applying knowledge of stem cell biology to advance therapies for hard-to-treat diseases in an ethical and rigorous manner. In addition to research, ISCI is a cell manufacturing facility for the Cardiovascular Cell Therapy Research Network (CCTRN), and has supplied cells to allow other researchers to conduct important work.