Cell therapy for heart failure: the need for a new therapeutic strategy.
ABSTRACT Improvements in the treatment of ischemic heart disease have led to a significant growth in the numbers of patients with systolic heart failure secondary to myocardial injury. Current therapies fail to address the loss of contractile tissue due to myocardial injury. Cell therapy is singular in its promise of primarily treating this underlying issue through salvage of viable myocardium or generation of new contractile tissue. Multiple cell types have been used to target acute myocardial infarction, chronic ischemic heart disease and heart failure due to infarction. Bone marrow mononuclear cells have been used to increase myocardial salvage after acute infarction. Randomized trials of over 800 patients have demonstrated no safety issues, and meta-analyses have suggested an improvement in left ventricular function in treated patients with trends toward improvements in hard cardiac end points. Cell therapy for chronic ischemic heart disease with bone marrow angiogenic progenitors has shown similar safety and trends toward improvement in function. While these therapies have targeted patients with viable myocardium, myoblasts have been used to treat patients with left ventricular dysfunction secondary to transmural infarction. Cell types with cardiomyogenic potential, including induced pluripotent stem cells and cardiac progenitor cells, offer the promise of true myocardial regeneration. Future studies with these cells may open the door for true myocardial regeneration.
Article: Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.[show abstract] [hide abstract]
ABSTRACT: Cardiovascular progenitor cells (CPCs) have been identified within the developing mouse heart and differentiating pluripotent stem cells by intracellular transcription factors Nkx2.5 and Islet 1 (Isl1). Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their in vitro expansion that maintain their multipotency. We sought to identify specific cell surface markers that label endogenous embryonic CPCs and validated these markers in iPSC-derived Isl1(+)/Nkx2.5(+) CPCs. We developed conditions that allow propagation and characterization of endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPCs and protocols for their clonal expansion in vitro and transplantation in vivo. Transcriptome analysis of CPCs from differentiating mouse embryonic stem cells identified a panel of surface markers. Comparison of these markers as well as previously described surface markers revealed the combination of Flt1(+)/Flt4(+) best identified and facilitated enrichment for Isl1(+)/Nkx2.5(+) CPCs from embryonic hearts and differentiating iPSCs. Endogenous mouse and iPSC-derived Flt1(+)/Flt4(+) CPCs differentiated into all three cardiovascular lineages in vitro. Flt1(+)/Flt4(+) CPCs transplanted into left ventricles demonstrated robust engraftment and differentiation into mature cardiomyocytes (CMs). The cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPC with trilineage cardiovascular potential in vitro and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs in vivo post transplantation into adult hearts.PLoS ONE 01/2012; 7(10):e45603. · 4.09 Impact Factor