Damaged Heart Tissue Repaired by Genetically Engineered Stem Cells from Aged Heart Attack Patients

Heart disease researchers have used human cardiac progenitor cells (hCPCs) taken from elderly heart attack patients to demonstrate how genetic engineering could rejuvenate these stem cells for use to repair damage to the heart muscle.

Investigators at San Diego State University (CA, USA) isolated hCPCs from the myocardium of heart failure patients undergoing left ventricular assist device implantation. Cultures of the hCPCs were then genetically engineered to express either green fluorescent protein (hCPCe) or Pim-1-GFP (hCPCeP). Green fluorescence-labeled cells and hCPCeP cells labeled with luciferase were tracked by noninvasive techniques after the cells had been injected into the myocardia of immunocompromised mice following infarction. Myocardial structure and function were monitored by echocardiographic and hemodynamic assessment of the mice for 20 weeks after delivery.

Pim-1 (proto-oncogene serine/threonine-protein kinase) is mainly involved in cell cycle progression, apoptosis, and transcriptional activation as well as more general signal transduction pathways. The gene for Pim-1 is expressed primarily in B-lymphoid and myeloid cell lines, and is overexpressed in hematopoietic malignancies and in prostate cancer. Its role in signal transduction contributes to both cell proliferation and survival, and thus provides a selective advantage in tumorigenesis. Pim-1 has also been found to be highly expressed in cell cultures isolated from human tumors.

Results published in the July 26, 2012, online edition of the Journal of the American College of Cardiology revealed that hCPCs isolated from failing myocardium and modified with Pim-1 possessed enhanced reparative potential relative to control hCPCs. Improvements mediated by hCPCs modified with Pim-1 were evident structurally and functionally, with durable human cellular persistence, engraftment, and acquisition of phenotypic characteristics consistent with differentiated myocardium. Enhanced persistence of hCPCeP versus hCPCe was revealed by bioluminescence imaging at up to eight weeks after delivery.

"Since patients with heart failure are normally elderly, their cardiac stem cells are not very healthy," said first author Dr. Sadia Mohsin, a post-doctoral researcher at San Diego State University. "We modified these biopsied stem cells and made them healthier. It is like turning back the clock so these cells can thrive again. Modifying aged human cardiac cells from elderly patients adds to the cell's ability to regenerate damaged heart muscle, making stem cell engineering a viable option. This is an especially exciting finding for heart failure patients. Right now we can only offer medication, heart transplantation, or stem cell therapies with modest regenerative potential, but PIM-1 modification offers a significant advance for clinical treatment."

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