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Stem cell therapy and breast cancer treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment.

Sharp TE, George JC - Front Oncol (2014)

Bottom Line: While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies.These new therapeutics should promote the regeneration of lost or deteriorating myocardium.Over the last several decades, the therapeutic potential of cell-based therapy has been investigated for HF patients.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, Temple University School of Medicine , Philadelphia, PA , USA.

ABSTRACT
A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF). This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM). While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades, the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review, we discuss the progress of pre-clinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

No MeSH data available.


Related in: MedlinePlus

Proposed mechanisms of stem cell-mediated repair. Transplantation of stem cells into the heart initiates repair of damaged tissue. The hypothesized repair mechanisms are both direct and indirect, trans-differentiation of stem cells into new cardiomyocytes and vascular cells, inhibition of apoptosis, mobilization of endogenous cell populations, alterations in ECM remodeling, and neovascularization. Collectively, these processes reduce adverse cardiac remodeling, increase the possibility of perfusion, repair/regenerate damaged tissues, and ultimately improve left ventricular cardiac pump function & patients clinical end-points. Illustration credit: Thomas E. Sharp III.
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Figure 1: Proposed mechanisms of stem cell-mediated repair. Transplantation of stem cells into the heart initiates repair of damaged tissue. The hypothesized repair mechanisms are both direct and indirect, trans-differentiation of stem cells into new cardiomyocytes and vascular cells, inhibition of apoptosis, mobilization of endogenous cell populations, alterations in ECM remodeling, and neovascularization. Collectively, these processes reduce adverse cardiac remodeling, increase the possibility of perfusion, repair/regenerate damaged tissues, and ultimately improve left ventricular cardiac pump function & patients clinical end-points. Illustration credit: Thomas E. Sharp III.

Mentions: With the plethora of basic science and clinical research performed on isolating and characterizing a number of adult stem cells to be utilized for cardiac cell therapy in the past two decades, we as a field still do not know which cell type, and/or combination of cells will be most beneficial. The work has yielded some rewards despite most questions still not having answers; we now understand that multiple tissues have population of stem cells that have the capacity to be beneficial toward heart function post injury and inhibit adverse remodeling, while improving quality of life in patients suffering from many different cardiac disease states (15, 16, 42, 50, 51, 56, 62, 64, 69, 83, 100, 102, 113). Despite not fully understanding the mechanism of action, the field has a general consensus on ways in which stem cell therapy is working to improve cardiac function (Figure 1); animal studies have shown beneficial effects of stem cell therapy through paracrine factor secretion (48, 99, 100), trans-differentiation into multiple cell types, which help to improve cardiac function (92, 116) and through homing of endogenous stem cells to the site of injury (48, 76). The cell types discussed above do not all work with the same mechanism of action; it has been demonstrated that MSCs most likely work through paracrine factor production and secretion (48, 51, 74, 117–119), while BMMNCs and CSCs have the ability to form new blood vessels for better perfusion (46, 47, 53–55, 59, 75–77, 79, 85, 86, 89, 96, 110, 120, 121) and create new myocyte from transplanted cells (53, 55, 64, 111–115, 122, 123). Below, we discuss the major mechanisms and how they may be beneficial toward patients suffering from cancer treatment-related cardiotoxicity.


Stem cell therapy and breast cancer treatment: review of stem cell research and potential therapeutic impact against cardiotoxicities due to breast cancer treatment.

Sharp TE, George JC - Front Oncol (2014)

Proposed mechanisms of stem cell-mediated repair. Transplantation of stem cells into the heart initiates repair of damaged tissue. The hypothesized repair mechanisms are both direct and indirect, trans-differentiation of stem cells into new cardiomyocytes and vascular cells, inhibition of apoptosis, mobilization of endogenous cell populations, alterations in ECM remodeling, and neovascularization. Collectively, these processes reduce adverse cardiac remodeling, increase the possibility of perfusion, repair/regenerate damaged tissues, and ultimately improve left ventricular cardiac pump function & patients clinical end-points. Illustration credit: Thomas E. Sharp III.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4217360&req=5

Figure 1: Proposed mechanisms of stem cell-mediated repair. Transplantation of stem cells into the heart initiates repair of damaged tissue. The hypothesized repair mechanisms are both direct and indirect, trans-differentiation of stem cells into new cardiomyocytes and vascular cells, inhibition of apoptosis, mobilization of endogenous cell populations, alterations in ECM remodeling, and neovascularization. Collectively, these processes reduce adverse cardiac remodeling, increase the possibility of perfusion, repair/regenerate damaged tissues, and ultimately improve left ventricular cardiac pump function & patients clinical end-points. Illustration credit: Thomas E. Sharp III.
Mentions: With the plethora of basic science and clinical research performed on isolating and characterizing a number of adult stem cells to be utilized for cardiac cell therapy in the past two decades, we as a field still do not know which cell type, and/or combination of cells will be most beneficial. The work has yielded some rewards despite most questions still not having answers; we now understand that multiple tissues have population of stem cells that have the capacity to be beneficial toward heart function post injury and inhibit adverse remodeling, while improving quality of life in patients suffering from many different cardiac disease states (15, 16, 42, 50, 51, 56, 62, 64, 69, 83, 100, 102, 113). Despite not fully understanding the mechanism of action, the field has a general consensus on ways in which stem cell therapy is working to improve cardiac function (Figure 1); animal studies have shown beneficial effects of stem cell therapy through paracrine factor secretion (48, 99, 100), trans-differentiation into multiple cell types, which help to improve cardiac function (92, 116) and through homing of endogenous stem cells to the site of injury (48, 76). The cell types discussed above do not all work with the same mechanism of action; it has been demonstrated that MSCs most likely work through paracrine factor production and secretion (48, 51, 74, 117–119), while BMMNCs and CSCs have the ability to form new blood vessels for better perfusion (46, 47, 53–55, 59, 75–77, 79, 85, 86, 89, 96, 110, 120, 121) and create new myocyte from transplanted cells (53, 55, 64, 111–115, 122, 123). Below, we discuss the major mechanisms and how they may be beneficial toward patients suffering from cancer treatment-related cardiotoxicity.

Bottom Line: While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies.These new therapeutics should promote the regeneration of lost or deteriorating myocardium.Over the last several decades, the therapeutic potential of cell-based therapy has been investigated for HF patients.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, Temple University School of Medicine , Philadelphia, PA , USA.

ABSTRACT
A new problem has emerged with the ever-increasing number of breast cancer survivors. While early screening and advances in treatment have allowed these patients to overcome their cancer, these treatments often have adverse cardiovascular side effects that can produce abnormal cardiovascular function. Chemotherapeutic and radiation therapy have both been linked to cardiotoxicity; these therapeutics can cause a loss of cardiac muscle and deterioration of vascular structure that can eventually lead to heart failure (HF). This cardiomyocyte toxicity can leave the breast cancer survivor with a probable diagnosis of dilated or restrictive cardiomyopathy (DCM or RCM). While current HF standard of care can alleviate symptoms, other than heart transplantation, there is no therapy that replaces cardiac myocytes that are killed during cancer therapies. There is a need to develop novel therapeutics that can either prevent or reverse the cardiac injury caused by cancer therapeutics. These new therapeutics should promote the regeneration of lost or deteriorating myocardium. Over the last several decades, the therapeutic potential of cell-based therapy has been investigated for HF patients. In this review, we discuss the progress of pre-clinical and clinical stem cell research for the diseased heart and discuss the possibility of utilizing these novel therapies to combat cardiotoxicity observed in breast cancer survivors.

No MeSH data available.


Related in: MedlinePlus