Transplanted Human Umbilical Cord Blood Cells Improved Long-Term Heart Muscle Structure and Function in Rats After a Heart Attack

Jianyi Zhang, from the University of Minnesota Health Science Center, in Minneapolis, Minnesota and his co-workers have shown that the transplantation of human umbilical cord blood cells into the rat hearts after a heart attack experience long-term effects that are not observed in the control animals that did not receive the stem cells. Furthermore, none of these laboratory animals required immunosuppressive therapy. The study is scheduled to be published in the journal Cell Transplantation.

“Myocardial infarction induced by coronary artery disease is one of the major causes of heart attack,” said Dr. Zhang. “Because of the loss of viable myocardium after an MI, the heart works under elevated wall stress, which results in progressive myocardial hypertrophy and left ventricular dilation that leads to heart failure. We investigated the long-term effects of stem cell therapy using human non-hematopoietic umbilical cord blood stem cells (nh-UCBCs). These cells have previously exhibited neuro-restorative effects in a rodent model of ischemic brain injury in terms of improved LV function and myocardial fiber structure, the three-dimensional architecture of which make the heart an efficient pump.”

According to Zhang and his co-authors, stem cell researchers have intently examined the ability of stem cells to regenerate and heal damaged heart tissue. Many laboratories all over the world have employed different types of stem cells, different animal models, and distinct modes of stem cell delivery into the heart tissue, and different stem cell doses. All of these studies have produced varying levels of improvement of left ventricular function. Zhang and others also note that, for the most part, the underlying mechanisms by which implanted stem cells improve heart function are “poorly understood and that the overall regeneration of heart muscle cells is modest at best.

In order to investigate the heart’s remodeling processes and to characterize the alterations in cardiac fiber architecture, Zhang’s team used diffusion tensor MRI (DTMRI), which has been previously used to study heart muscle fiber structure in both humans and animals. Most previous studies have concentrated on the short-term effects of umbilical cord blood cells (UCBCs) on damaged heart muscles. Fortunately, this study, which examined the long-term effects of UCBCs, not only demonstrated evidence of significantly improved heart function in treated rats, but also showed evidence of delay and prevention of myocardial fiber structural remodeling. Keep in mind that such alterations in heart muscle fiber structure could have resulted in heart failure.

When compared to the age-matched but untreated rat hearts that had suffered a heart attack, the regional heart muscle function of non-hematopoietic UCBC-treated hearts was significantly improved and the preserved myocardial fiber structure seems to have served as an “underlying mechanism for the observed function improvements.”

“Our data demonstrate that nh-UCBC treatment preserves myocardial fiber structure that supports the improved LV regional and chamber function,” concluded the researchers.

“This study provides evidence that UCBCs could be a potential therapy with long-term benefits for MI” said Dr. Amit N. Patel, director of cardiovascular regenerative medicine at the University of Utah and section editor for Cell Transplantation. “Preservation of the myocardial fiber structure is an important step towards finding an effective therapy for MIs”

See: Chen, Y.; Ye, L.; Zhong, J.; Li, X.; Yan, C.; Chandler, M. P.; Calvin, S.; Xiao, F.; Negia, M.; Low, W. C.; Zhang, J.; Yu, X. The Structural Basis of Functional Improvement in Response to Human Umbilical Cord Blood Stem Cell Transplantation . Cell Transplant. Appeared or available online: December 10, 2013.

New Analysis of Stem Cell Treatments for Spinal Cord Injury in Laboratory Animals

A host of preclinical studies have examined the ability of stem cells to improve the condition of laboratory animals that have suffered a spinal cord injury. While these studies vary in their size, design, and quality, there has been little cumulative analysis of the data generated by these studies.

Fortunately, there is a powerful analytical tool that can examine data from many studies and this type of analysis is called a “meta-analysis.” Meta-analyses use sophisticated statistical packages to systematically reassess a compilation of the data contained within these papers. Meta-analyses are exhausting, but potentially very useful. Such a meta-analysis is also very important because it provides researchers with an indication of what problems must be worked out before these treatments advance to human clinical trials and what aspects of the treatment work better than others.

A recent meta-analysis of stem cell therapy on animal models of spinal cord injury has been published by Ana Antonic, MSc, David Howells, Ph.D., and colleagues from the Florey Institute and the University of Melbourne, Australia, along with Malcolm MacLeod and colleagues from the University of Edinburgh, UK in the open access journal PLOS Biology.

The goal of regenerative spinal cord treatments is to use stem cells to replace dead cells within damaged areas of the spinal cord. Such treatments would be given to spinal cord injury patients in the hope of improving the ability to move and to feel below the site of the injury. Many experiments that utilize animal models of spinal cord injury have used stem cells to treat laboratory animals that have suffered spinal cord injury, but, unfortunately, these studies are limited in scale by size (as a result of financial considerations), practical and ethical considerations. Such limitations hamper each individual study’s statistical power to detect the true effects of the stem cell implantation. Also, these studies use different types of stem cells in their treatment scenarios, inject those cells differently induce spinal cord injuries differently, and test their animals for functional recovery differently.

To assess these studies, this new paper examined 156 published studies, all of which tested the effects of stem cell treatments on about 6,000 spinal cord-injured animals.

Overall, they found that stem cell treatment results in an average improvement of about 25 percent over the post-injury performance in both sensory (ability to feel) and motor (ability to move) outcomes. Unfortunately, the variation from one animal to another varied widely.

For sensory outcomes the degree of improvement tended to increase with the number of cells implanted. Such dose-responsive results tend to indicate that the improvements are actually due to the stem cells, and therefore, this stem cell-mediated effect represents a genuine biological effect.

The authors also measured the effects of bias. Simply put, if the experimenters knew which animals were treated and which were untreated, then they might be more likely to report improvements in the stem cell-treated animals. They also examined the way that the stem cells were cultured, the way that the spinal injury was generated and the way that outcomes were measured. In each case, important lessons were learned that should help inform and refine the design of future animal studies.

The meta-analysis also revealed some surprises that should provoke further investigations. For example, there was little evidence that female animals showed any beneficial sensory effects as a result of stem cell treatments. Also, the efficacy of the stem cell treatment seemed to not depend on whether immunosuppressive drugs were administered or not.

The authors conclude, “Extensive recent preclinical literature suggests that stem cell-based therapies may offer promise; however the impact of compromised internal validity and publication bias means that efficacy is likely to be somewhat lower than reported here.”

Even though human clinical trials are in the works, such trials will continue to be informed by preclinical studies on laboratory animals.