Limits...
Challenges for heart disease stem cell therapy.

Hoover-Plow J, Gong Y - Vasc Health Risk Manag (2012)

Bottom Line: Cardiovascular diseases (CVDs) are the leading cause of death worldwide.The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy.This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

View Article: PubMed Central - PubMed

Affiliation: Departmentof Cardiovascular Medicine, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA. hooverj@ccf.org

ABSTRACT
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

Show MeSH

Related in: MedlinePlus

Expansion of stem cells.Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2012. All Rights Reserved.Notes: Currently, increased numbers of autologous hematopoietic, mesenchymal, cardiac, endothelial, and skeletal stem cells can be generated by expansion in culture with proliferation specific conditions. Adult cells such as fibroblasts or adipocytes may be dedifferentiated in culture to stem cells (iPS cells). MSCs, iPS cells, and ESCs can be induced to differentiate and proliferate in cell culture. Use of differentiated MSCs, iPS cells, and ESCs is in preclinical development.Abbreviations: ESC, embryonic stem cell; iPS, induced pluripotent stem; MSC, mesenchymal stem cell.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3295632&req=5

f2-vhrm-8-099: Expansion of stem cells.Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2012. All Rights Reserved.Notes: Currently, increased numbers of autologous hematopoietic, mesenchymal, cardiac, endothelial, and skeletal stem cells can be generated by expansion in culture with proliferation specific conditions. Adult cells such as fibroblasts or adipocytes may be dedifferentiated in culture to stem cells (iPS cells). MSCs, iPS cells, and ESCs can be induced to differentiate and proliferate in cell culture. Use of differentiated MSCs, iPS cells, and ESCs is in preclinical development.Abbreviations: ESC, embryonic stem cell; iPS, induced pluripotent stem; MSC, mesenchymal stem cell.

Mentions: A critical step for improved SC therapy is the expansion of accessible SCs (Figure 2). The homing of cells to injured tissues is very inefficient, and increasing the number of cells that are available for treatment would be beneficial. Autologous BM cells, adipose tissue, myocardial, and UCB are cultured ex vivo to increase the number of cells. Culturing the tissue also allows selection of specific cells. The ESCs and iPS cells require additional steps prior to expansion of a preparation. The iPS cells require de-differentiation as an initial step and then both iPS cells and ESCs are induced to differentiate prior to expansion. SCs in culture form colonies, and proliferation without differentiation requires a specific sequence and timing of the availability of growth factors and cytokines.59–66 In addition, these cells must maintain their pluripotency. Cells need to be free of feeder-cells, serum proteins, and microbial agents. Large-scale expansion with maintenance of pluripotency and transplant safety is required.58,67 Currently, effective cell culture proliferation is limited,61 and further studies are needed to understand the requirements for expansion. New approaches are being investigated including the use of nanofibers with growth factors, mesenchymal stromal cells in cultures of HSCs, and genetic manipulation of UCB HSCs.68–72 To improve SC therapy, improved methods of SC ex vivo expansion are required.


Challenges for heart disease stem cell therapy.

Hoover-Plow J, Gong Y - Vasc Health Risk Manag (2012)

Expansion of stem cells.Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2012. All Rights Reserved.Notes: Currently, increased numbers of autologous hematopoietic, mesenchymal, cardiac, endothelial, and skeletal stem cells can be generated by expansion in culture with proliferation specific conditions. Adult cells such as fibroblasts or adipocytes may be dedifferentiated in culture to stem cells (iPS cells). MSCs, iPS cells, and ESCs can be induced to differentiate and proliferate in cell culture. Use of differentiated MSCs, iPS cells, and ESCs is in preclinical development.Abbreviations: ESC, embryonic stem cell; iPS, induced pluripotent stem; MSC, mesenchymal stem cell.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3295632&req=5

f2-vhrm-8-099: Expansion of stem cells.Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2011–2012. All Rights Reserved.Notes: Currently, increased numbers of autologous hematopoietic, mesenchymal, cardiac, endothelial, and skeletal stem cells can be generated by expansion in culture with proliferation specific conditions. Adult cells such as fibroblasts or adipocytes may be dedifferentiated in culture to stem cells (iPS cells). MSCs, iPS cells, and ESCs can be induced to differentiate and proliferate in cell culture. Use of differentiated MSCs, iPS cells, and ESCs is in preclinical development.Abbreviations: ESC, embryonic stem cell; iPS, induced pluripotent stem; MSC, mesenchymal stem cell.
Mentions: A critical step for improved SC therapy is the expansion of accessible SCs (Figure 2). The homing of cells to injured tissues is very inefficient, and increasing the number of cells that are available for treatment would be beneficial. Autologous BM cells, adipose tissue, myocardial, and UCB are cultured ex vivo to increase the number of cells. Culturing the tissue also allows selection of specific cells. The ESCs and iPS cells require additional steps prior to expansion of a preparation. The iPS cells require de-differentiation as an initial step and then both iPS cells and ESCs are induced to differentiate prior to expansion. SCs in culture form colonies, and proliferation without differentiation requires a specific sequence and timing of the availability of growth factors and cytokines.59–66 In addition, these cells must maintain their pluripotency. Cells need to be free of feeder-cells, serum proteins, and microbial agents. Large-scale expansion with maintenance of pluripotency and transplant safety is required.58,67 Currently, effective cell culture proliferation is limited,61 and further studies are needed to understand the requirements for expansion. New approaches are being investigated including the use of nanofibers with growth factors, mesenchymal stromal cells in cultures of HSCs, and genetic manipulation of UCB HSCs.68–72 To improve SC therapy, improved methods of SC ex vivo expansion are required.

Bottom Line: Cardiovascular diseases (CVDs) are the leading cause of death worldwide.The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy.This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

View Article: PubMed Central - PubMed

Affiliation: Departmentof Cardiovascular Medicine, Joseph J Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195, USA. hooverj@ccf.org

ABSTRACT
Cardiovascular diseases (CVDs) are the leading cause of death worldwide. The use of stem cells to improve recovery of the injured heart after myocardial infarction (MI) is an important emerging therapeutic strategy. However, recent reviews of clinical trials of stem cell therapy for MI and ischemic heart disease recovery report that less than half of the trials found only small improvements in cardiac function. In clinical trials, bone marrow, peripheral blood, or umbilical cord blood cells were used as the source of stem cells delivered by intracoronary infusion. Some trials administered only a stem cell mobilizing agent that recruits endogenous sources of stem cells. Important challenges to improve the effectiveness of stem cell therapy for CVD include: (1) improved identification, recruitment, and expansion of autologous stem cells; (2) identification of mobilizing and homing agents that increase recruitment; and (3) development of strategies to improve stem cell survival and engraftment of both endogenous and exogenous sources of stem cells. This review is an overview of stem cell therapy for CVD and discusses the challenges these three areas present for maximum optimization of the efficacy of stem cell therapy for heart disease, and new strategies in progress.

Show MeSH
Related in: MedlinePlus