The latest in cardiovascular research in a special issue of Cell Transplantation

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Putnam Valley, NY. (April 18, 2016) – In a special issue of Cell Transplantation dedicated to cell transplantation for cardiovascular regenerative medicine, three papers discuss the use of transplanted umbilical cord cells, activation of endogenous cardiac stem cells, and transplanted bone marrow-derived mononuclear cells to treat cardiovascular diseases.

Clinical trial using bone marrow cells to treat heart failure

Using a multi-cell therapy called Ixmyelocel, produced from a patient's (autologous) own bone marrow mononuclear cells (BM-MNCs), an ongoing clinical trial named "ixCELL-DCM" is being conducted in various locations in the U.S. for patients with heart failure. Because BM-MNC therapy requires a large number of cells, the cells are biologically enhanced to provide immune therapy to the myocardium for patients with heart failure.

"Heart failure continues to be a major cause of morbidity and mortality in the U.S.," said study co-author Dr. Timothy D. Henry of the Cedars-Sinai Heart Institute in Los Angeles. "Despite medical advances, mortality continues to approach 50 percent within five years."

The ixCELL-DCM trial is the first double-blind, placebo-controlled study of ixmyelocel-T administered by catheter injections to patients with heart failure (HF), according to the researchers. Ixmyelocel-T differs from other heart cell therapies because it contains "a complete range of BM-MNC types, but with selective expansion" of certain cell types to provide immune therapy. The year-long study to assess efficacy, safety and tolerability is being conducted for a small number of qualified HF patients with ischemic dilated cardiomyopathy (IDCM) after earlier trials suggested that ixmyeolocel-T might improve clinical, functional, symptomatic, and quality of life outcomes in patients with IDCM.

Contact: Dr. Timothy D. Henry, 127 S. San Vincente Blvd. Suite A3100, Los Angeles, CA 90048

Ph: (424) 315-2699 Fax: (310) 423-3522 Email: [email protected]

Citation: Henry TD, Schaer GL, DeMaria A, Recker D, Remmers AE, Goodrich J, Patel AN. The iXCELL-DCM Trial: Rationale and Design. Cell Transplant. Appeared or available on-line: March 22, 2016.

This study, scheduled to be published later this year in a special cardiovascular issue of Cell Transplantation, is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1575_Henry_et_al

Activation of endogenous cardiac stem cells

A natural peptide called Apelin-13 acts as a mediator for blood pressure and blood flow and is a strong stimulator of cardiac contractility, playing a role in cardiac tissue remodeling. After the apelin pathway was found to contribute to heart tissue regeneration and functional recovery after cell transplantation with bone marrow-derived mesenchymal stem cells in previous studies with animal models, researchers in Beijing, China carried out further investigation using apelin-13 alone to regenerate the heart in pre-clinical studies.

According to study authors there has been "a critical need to develop strategies to activate the heart's own, intrinsic cardiac regenerative potential using endogenous (the patients' own) proteins."

"While little is known about whether apelin may mobilize endogenous cardiac stem cells, our results have shown that a small amount of apelin-13 administered by injection into rats modeled with myocardial infarction (commonly called "heart attacks") can lead to a significant increase in cardiac stem cell proliferation. It also resulted in significant reductions in infarct size and improvement of cardiac function," said study co-author Dr. Yi Cao of the Center of Cardiology, Navy General Hospital in Beijing, China. "Our experimental data further strengthens the understanding of the mechanism by which apelin promotes cardiac repair and functional recovery post-MI by activating stem cells or progenitors."

Contact: Dr. Yi Cao, The Center of Cardiology, Navy General Hospital, N6 Fucheng Rd. 100048, Beijing, China

Ph: +86-10-66958481 Fax: 86-10-68780127 Email: [email protected]

Citation: Zhang NK, Cao Y, Zhu ZM, Zheng N, Wang L, Hong X, Gao LR. Activation of endogenous cardiac stem cells by apelin-13 in infarcted rat heart. Cell Transplant. Appeared or available on-line: February 26, 2016.

This study, scheduled to be published later this year in a special cardiovascular issue of Cell Transplantation, is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-1508_Zhang_et_al

Delivery of allogeneic umbilical cord lining sub-epithelial cells

"The goal of this study was to evaluate the safety and feasibility of delivering doses of allogeneic (other-donated) umbilical cord lining sub-epithelial cells (UCSECs) to patients with heart failure," said Dr. Amit N. Patel, director of clinical regenerative medicine at the University of Utah and section editor for Cell Transplantation. "Patients received a single dose of either 100 million (M), 200 M or 400 M cells and were followed for two years."

The researchers reported that all 18 patients enrolled in the study and were infused without complications. Those patients receiving 200 M and 400 M cell doses presented a "signal" for early improvements in left ventricle function.

"There was a statistically significant decrease in B-type naturetic peptide (BNP) in patients receiving 200 M or 400 M doses," said the researchers. BNP is a substance secreted from the ventricles or lower chambers of the heart in response to changes in pressure that occur when heart failure develops and worsens.

The study provides the basis for a larger clinical trial in heart failure using moderate or high doses of UCSECs, concluded the researchers. "The combination of improving clinical measures and biomarkers are an interesting trend which would be better defined in a larger dose study in similar patients," they said. "The exact mechanism for improvement with stem cell therapy remains a topic for conjecture and should be further explored."

Contact: Dr. Amit N. Patel, University of Utah, 30 N 1900 E SOM 3c127 Salt Lake City, UT 84132

Ph: (801) 587-7946 Fax: (801) 585-3936 Email: [email protected]

Citation: Tuma J, Carrasco A, Castillo J, Cruz C, Carrillo A, Ercilla J, Yarleque C, Cunza J, Bartlett CE, Winters AA, Silva FJ, Patel AN. RESCUE-HF Trial: Retrograde Delivery of Allogeneic Umbilical Cord Lining Sub-Epithelial Cells in Patients with Heart Failure. Cell Transplant. Appeared or available on-line: January 13, 2016.

This study, scheduled to be published later this year in a special cardiovascular issue of Cell Transplantation, is currently freely available on-line as an unedited early e-pub at: http://www.ingentaconnect.com/content/cog/ct/pre-prints/content-CT-2580_Tuma_et_al

"These studies are merely a few highlights of the special cardiovascular issue," said Dr. Amit N. Patel, director of clinical regenerative medicine at the University of Utah and section editor for Cell Transplantation. "Cardiovascular diseases such as stroke and heart disease are increasing in prevalence as the population ages, thereby necessitating the development of new therapies that serve to lesson mortality and restore functional improvement. This issue focusses on the latest developments in cell therapy for cardiovascular diseases as well as therapies aimed at upregulating the body's own repair mechanisms. These are all topics that are highly relevant for the field."

The Coeditors-in-Chief for CELL TRANSPLANTATION are at the Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, Tampa, FL, USA and the Center for Neuropsychiatry, China Medical University Hospital, TaiChung, Taiwan. Contact: Paul R. Sanberg at [email protected], Shinn-Zong Lin at [email protected], or Associate Editor Samantha Portis at [email protected]

News release by Florida Science Communications http://www.sciencescribe.net

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