New Tool for Stem Cell Transplantation into the Heart


Researchers from the famed Mayo Clinic, in collaboration with scientists at a biopharmaceutical biotechnology company in Belgium have invented a specialized catheter for transplanting stem cells into a beating heart.

This new device contains a curved needle with graded openings along the shaft of the needle. The cells are released into the needle and out through the openings in the side of the needle shaft. This results in maximum retention of implanted stem cells to repair the heart.

“Although biotherapies are increasingly more sophisticated, the tools for delivering regenerative therapies demonstrate a limited capacity in achieving high cell retention in the heart,” said Atta Behfar, the lead author of this study and a cardiologist. “Retention of cells is, of course, crucial to an effective, practical therapy.”

Researchers from the Mayo Clinic Center for Regenerative Medicine in Rochester, MN and Cardio3 Biosciences in Mont-Saint-Guibert, Belgium, collaborated to develop the device. Development of this technology began by modeling the dynamic motions of the heart in a computer model. Once the Belgium group had refined this computer model, the model was tested in North America for safety and retention efficiency.

These experiments showed that the new, curved design of the catheter eliminates backflow and minimizes cell loss. The graded holes that go from small to large diameters decrease the pressures in the heart and this helps properly target the cells. This new design works well in healthy and damaged hearts.

Clinical trials are already testing this new catheter. In Europe, the CHART-1 clinical trial is presently underway, and this is the first phase 3 trial to examine the regeneration of heart muscle in heart attack patients.

These particular studies are the culmination of years of basic science research at Mayo Clinic and earlier clinical studies with Cardio3 BioSciences and Cardiovascular Centre in Aalst, Belgium, which were conducted between 2009 and 2010.  This study, the C-CURE or Cardiopoietic stem Cell therapy in heart failURE study examined 47 patients, (15 control and 32 experimental) who received injections of bone marrow-derived mesenchymal stem cells from their own bone marrow into their heart muscle.  Control patients only received standard care.  After six months, those patients who received the stem cell treatment showed an increase in heart function and the distance they could walk in six minutes.   No adverse effects were observed in the stem cell recipients.

This study established the efficacy of mesenchymal stem cell treatments in heart attack patients.  However, other animal and computer studies established the efficacy of this new catheter for injecting heart muscle with stem cells.  Hopefully, the results of the CHART-1 study will be available soon.

Postscript:  The CHART-2 clinical trial is also starting.  See this video about it.

Induced Pluripotent Stem Cells Self-Repair a Chromosome Abnormality


Japanese and American scientists have made a fantastic discovery. An incurable type of chromosomal abnormality, in which one end of the chromosome has fused with the other, is known as a “ring chromosome.” The presence of ring chromosomes often correlates with neurological abnormalities. The collaborative work by these two researcher groups has shown that if induced pluripotent stem cells are derived from abnormal adult cells that contain ring chromosomes will spontaneously repair themselves.

This research team, which included researchers from Kyoto University professor and iPS cell pioneer Shinya Yamanaka, also included Yohei Hayashi and other researchers from the U.S.-based Gladstone Institutes.

“I was very surprised at the results,” said Hayashi. “There still remains a risk, but the findings may lead to the development of breakthrough treatment for chromosomal abnormalities.”

Normal chromosomes pairs consist of two rod-shaped chromosomes, but in the case of a ring chromosome, the arms of one of the two chromosomes are fused to form a ring.

Ring chromosomes tend to be associated with mental disabilities and growth retardation, and there are no therapeutic strategies for ring chromosomes.

Hayashi and his colleagues developed iPS cells from skin cells of patients with ring chromosome disorder to study the effects of this chromosomal defect in stem cells. However, the ring chromosomes could not be observed in the engineered iPS cells made from this patient’s cells.

For reasons still unknown, only normal chromosomes survived, according to the researchers. Typically, a cell that contains ring chromosomes divides into two abnormal cells in the normal mitotic process.

These findings were published in the online edition of the British science journal Nature on Jan. 13, 2014.

An Even Better Way to Make Induced Pluripotent Stem Cells


Researchers from the Centre for Genomic Regulation in Barcelona, Spain, have discovered an even faster and more efficient way to reprogram adult cells to make induced pluripotent stem cells (iPSCs).

This new discovery decreases the time it takes to derived iPSCs from adult cells from a few weeks to a few days. It also elucidated new things about the reprogramming process for iPSCs and their potential for regenerative medical applications.

iPSCs behave similarly to embryonic stem cells, but they can be created from terminally differentiated adult cells. The problem with the earlier protocols for the derivation of iPSCs is that only a very small percentage of cells were successfully reprogrammed (0.1%-2%). Also this reprogramming process takes weeks and is a rather hit-and-miss process.

The Centre for Genomic Regulation (CRG) research team have been able to reprogram adult cells very efficiently and in a very short period of time.

“Our group was using a particular transcription factor (C/EBPalpha) to reprogram one type of blood cells into another (transdifferentiation). We have now discovered that this factor also acts as a catalyst when reprogramming adult cells into iPS,” said Thomas Graf, senior group leader at the CRG and ICREA research professor.

“The work that we’ve just published presents a detailed description of the mechanism for transforming a blood cell into an iPS. We now understand the mechanics used by the cell so we can reprogram it and make it become pluripotent again in a controlled way, successfully and in a short period of time,” said Graf.

Genetic information is compacted into the nucleus like a wadded up ball of yarn. In order to access genes for gene expression, that ball of yarn has to be unwound so that the cell can find the information it needs.

The C/EBPalpha (CCAAT/Enhancer Binding Protein alpha) protein temporarily unwinds that region of DNA that contains the genes necessary for the induction of pluripotency. Thus, when the reprogramming process begin, the right genes are activated and they enable the successful reprogramming all the cells.

“We already knew that C/EBPalpha was related to cell transdifferentiation processes. We now know its role and why it serves as a catalyst in the reprogramming,” said Bruno Di Stefano, a PhD student. “Following the process described by Yamanaka the reprogramming took weeks, had a very small success rate and, in addition, accumulated mutations and errors. If we incorporate C/EBPalpha, the same process takes only a few days, has a much higher success rate and less possibility of errors, said Di Stefano.

This discovery provides a remarkable insight into stem cell-forming molecular mechanisms, and is of great interest for those studies on the early stages of life, during embryonic development. At the same time, the work provides new clues for successfully reprogramming cells in humans and advances in regenerative medicine and its medical applications.