Umbilical Cord Blood Banking for Future Regenerative Therapies


Parents of a child who has been diagnosed in utero with a congenital heart defect, such as Hypoplastic Left Heart Syndrome (HLHS), often learn during pregnancy about banking the child’s umbilical cord blood. Susana Cantero Peral, M.D., a postdoctoral researcher who specializes in cord blood for the Todd and Karen Wanek Family Program for HLHS, talked with me about collecting, banking and the potential regenerative properties of cord blood. 

When you decide to bank your baby’s cord blood, what is actually collected is the blood that remains in the blood vessels of the placenta and in the portion of the umbilical cord attached to it. Umbilical cord blood contains all of the normal elements of blood – red cells, white cells, platelets and plasma. It is also rich in hematopoietic (blood-forming) stem cells, similar to those found in bone marrow, which has been used to treat more than 80 different diseases, with leukemia being the most common disease category. Most of these transplants have been performed from unrelated cord blood units donated to public cord blood banks.

Umbilical cord blood was first used in transplant medicine in 1988, as an alternative source to bone marrow. At that time, the potential for these cells was not known, and some hematologists and transplants physicians regarded that new source of stem cells as “science fiction.” Today, clinical trials using umbilical cord blood for regenerative purposes are now becoming a reality in the field of regenerative medicine, and the HLHS program here at Mayo Clinic hopes to begin its own trials soon.

The HLHS program is doing ongoing research with the mononuclear cells found in cord blood. These cells are a subpopulation of leukocytes or white blood cells, which are important for fighting against infections. Mononuclear cells include lymphocytes and monocytes, and it is in this within this part of the blood that we can find the stem and progenitor cells.

“In addition to its use as an alternative to bone marrow for hematopoietic stem cell transplantation, cord blood has recently been used in a variety of regenerative medicine applications,” says Dr. Cantero Peral. “Some researchers have shown that cord blood contains a mixture of stem cells capable of giving rise to any cell of the body.  Several cells of non-hematopoietic lineage, or which can differentiate into non-hematopoietic cells, have been identified in the mononuclear fraction.”

Preclinical investigations have employed umbilical cord blood mononuclear cells in the therapy of neurologic disease (stroke, spinal cord, or brain trauma, amyotropic lateral sclerosis), cardiac disease (myocardial infarction or ischemia, cardiac injury, valve repair), and tissue repair.

“Some ongoing clinical trials are studying mainly the safety and efficacy of autologous cord blood cells in diseases such as cerebral palsy, stroke in children, pediatric traumatic brain injury, neonatal hypoxic-ischemic encephalopathy, autism, peripheral vascular disease and type 1 diabetes,” says Dr. Cantero Peral.

It is the goal of the HLHS program to delay or prevent heart transplant for those affected with HLHS. One of the ways we hope to do that is by delivering cell based therapies to those affected with HLHS.

“Umbilical cord blood cells are unique in their ability to differentiate into many cell types and provide a nurturing environment that supports cell growth and development. By transplanting these cell types into damaged tissues such as the heart muscle, we believe the damaged tissue will be stimulated to undergo maximal regeneration or tissue renewal,” says Timothy Nelson, M.D., director of the Todd and Karen Wanek Program for HLHS. “Therefore, this type of cell may provide a readily available cell source for congenital heart disease patients and offer a new strategy to improve the strength and function of treated heart muscle.”

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The Goals of the Imaging and Outcomes Component of the HLHS Research Program


Imaging and Outcome team (from left to right): Mark A. Bransford; Timothy M. Olson, M.D.; Patrick W. O’Leary, M.D.; Benjamin W. Eidem, M.D.; Karen P. Krucker, R.N.; Phillip M. Young, M.D.; Angela R. Miller, R.D.C.S.; and Chelsea L. Reece, R.D.C.S.

The primary goal of the imaging and outcomes component of the Todd and Karen Wanek Family Program for HLHS is to develop better methods of evaluating heart function in HLHS. Echocardiography (cardiac ultrasound) is the most common clinical test ordered and ejection fraction is the “number” most often used to evaluate the performance of heart muscle.  However, the best echocardiographic methods for assessing heart function were designed for the left ventricle in individuals with two ventricles (or at least a single left ventricle).

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Life Over the Rainbow


In honor of CHD awareness week, the people of the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome at Mayo Clinic would like to express our gratitude to all of our families that have participated in our research, inquired and helped spread the word.  It is because of each and every one of you that better outcomes for people with HLHS will come to fruition. Again, we thank you!

As we work toward our vision of delaying or preventing heart transplant for people with HLHS, the program’s overall goal is to initiate clinical trials that bring the latest advances in cell therapy to people with HLHS. Ultimately, we hope this knowledge will transcend HLHS to improve the lives of those affected with other Congenital Heart Defects as well.  It is the faces we see every day, much like the beautiful faces in this video, which will continue to drive us to fulfilling our vision and encourage all of us to never stop dreaming about life over the rainbow.

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Sisters by Heart


We here at the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome often hear about organizations providing support to families affected by congenital heart disease – one of those being Sisters by Heart, a group offering support and hope to families with newly diagnosed children with HLHS. Stacey Lihn, president of Sisters by Heart, tells us how the group got started and what it is currently doing to provide hope to families affected by HLHS…

A recent recipient HLHSer, post-Norwood, with his care package.
Photos courtesy of Sisters by Heart.

It all started with just one email via social media amongst fellow moms – moms of children who were born with Hypoplastic Left Heart Syndrome (HLHS) – and Sisters by Heart was born. Active within the online “heart community,” we heard about new HLHS diagnoses on a near-daily basis. When we read a blog post from an expecting mom about how she broke down in the middle of Babies ‘R Us, unable to find anything her son could wear after his upcoming open heart surgery (http://parkersfight.blogspot.com/2010/12/praying-for-miracle.html), the founding members of Sisters by Heart jumped into action. From one email and a care package, Sisters by Heart came to fruition. Within a few days, we had a logo, a website and several care packages shipped to families expecting their HLHS infants.

Sisters by Heart is a non-profit 501(c)(3) organization supporting newly diagnosed HLHS families by offering hope and a variety of resources for the HLHS community. 

Sisters by Heart began in December of 2010 with ten founding members, serving just a few families. Since then, we’ve added three board members, provided care packages to over 400 newly diagnosed families, and provided information and opportunities for the HLHS community to connect.  All in all, this is no small feat for a congenital heart defect affecting approximately 2 in 10,000 live births.

With growing popularity in the past year, we saw a significant need to “link” families up with each other.  And so, Sisters by Heart launched Linked by Heart (http://www.linked-by-heart.org/) – an avenue for HLHS families to connect with each other and learn about others’ stories and experiences with HLHS. As soon as Linked by Heart launched, the network grew and we’ve seen a steady incline over the past several months.  For the families we serve, locating “like-minds” in the midst of an HLHS journey can be greatly beneficial – in gaining a sense of normalcy, finding hope through others’ journeys and empowering one another to share information, research and knowledge.  

As we enter our third year as an organization, all of us at Sisters by Heart are honored and humbled to continue providing HOPE to HLHS families in the United States and Canada, as well as a multitude of resources specific to HLHS.   

We are grateful and proud to partner with top cardiac centers across the country, including Mayo Clinic, who support our mission, understand the importance and benefit of supportive networks, and provide updated research and information to our HLHS community.  All members of Sisters by Heart and Linked by Heart are volunteers and our specialized care packages are funded wholly by donors.

Our inspiration is fueled by the families to whom we serve and offer hope:


“The support that Sisters by Heart gives to new families with HLHS does not just end with their lovely and thoughtful care packages. That is just the beginning. To know you are not alone and have a sense of community is priceless.”
~ Sarah, mom to Cecilia

 

Our program would like to express our gratitude for the support Sisters by Heart provides to families affected with HLHS, and send a big congratulations on the start of their third year as an organization! Thank you for what you do!

To learn more about Sisters by Heart, nominate a newly diagnosed HLHS family for a care package, or support its mission with a monetary donation, please visit www.sisters-by-heart.org/

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A Piece of My Heart, From My Arm


In case you missed it, check out Nightline reporter Bill Weir’s return visit to Mayo Clinic.  Dr. Timothy Nelson and the entire Todd and Karen Wanek Family Program for HLHS team are currently using the technology shown in his video below, in conjunction with genetics research and clinical research, to gain insight into Hypoplastic Left Heart Syndrome and to ultimately develop innovative treatment options for people with HLHS.

 

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Nightline’s Bill Weir “checks in”


Bill visits with Sophie at her home in Minnesota.

 As he promised, Nightline’s Bill Weir recently returned to visit the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome to watch his heart tissue, bioengineered from a piece of his skin, beat outside of his body. While he was here, he spent some time with Sophie, a 3-year-old HLHS warrior from Minnesota, and her family who has already contributed to HLHS research in a big way. It is because of the many families like Sophie’s that we will find better solutions for those affected with HLHS. Watch the whole story on Nighline on ABC, on Friday at 11:35 p.m. central standard time.

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Genetic Investigations into HLHS- Part 2


In follow up to Genetic Investigations into HLHS- part 1,  we sat down with Dr. Timothy Olson, a pediatric cardiologist with a research focus in cardiovascular genetics at Mayo Clinc in Rochester to discuss whole genome sequencing, the second research strategy he uses to study HLHS genetics. If we think about the human genome as a book, whole genome sequencing would look at every single letter in the book.

In part 1, we talked about aCGH, which detects larger pieces of DNA - or, using book example, several pages or even a whole chapter of the book - that are either missing from the genetic blue print or extra pieces of genetic material. Having too little or too much of a series of genes can cause problems.

Genetics research is only possible through the participation of families, so this research begins with recruiting individuals with HLHS and their family members and collecting a sample – typically a blood sample - from which DNA is extracted.  “We study the DNA, and we use a very new technique that enables us to survey the entire genome, which is called Next Generation Sequencing or Whole Genome Sequencing,” explains Dr. Olson.  “This allows us to identify point mutations, genetic flaws in essence,  in a single letter of the genetic code.” The objective  is to try and pinpoint the defect or flaw within the genetic code that leads to the underdevelopment of the left side of the heart in HLHS. 

“Once we’ve done that, we can begin to understand some of the mechanisms and biological pathways that are important in normal development of the heart and which, when disrupted, lead to HLHS,” says Dr. Olson. 

The ultimate goal of the Todd and Karen Wanek Program for Hypoplastic Left Heart Syndrome  is to use a cell-based therapy to maintain the health of the right ventricle. Dr. Olson says, “If we can understand the genetic underpinnings, it may help us customize the cells that we use for therapy.  In some cases, because we are using cells from a patient’s own body, we may have to think about correcting the genetic defect that exists within those cells before we deliver those cells back to the patient to be used therapeutically.”

To learn more about the genetics research going on the program, read more on the genetics page of the program’s website.   

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What about stem cells for HLHS?


Thanks to the participation of families affected by HLHSTimothy Nelson, M.D., Ph.D. director of Mayo Clinic’s Regenerative Medicine Consult Service and the Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome, along with his team, are working to fulfill one of the program’s goals: to develop a regenerative therapy for HLHS. Determining which types of stem cells have the most potential for those affected with HLHS is one of the first steps.

Most people think of embryonic cells when they hear the term “stem cell.” Interestingly, there are many types of stem cells that reside in human tissue and some that can be created in the lab. The most common types of stem cells are: embryonic, perinatal, adult and bioengineered (lab-created). Dr Nelson’s research focus is perinatal stem cells found in umbilical cord blood, adult stems cells found in bone marrow, and bioengineered cells.

So, what is the difference, and what do they do? To learn more, watch Dr. Nelson discuss stem cells and their importance in the video below.

Currently, the answer is there is no approved stem cell therapy for heart repair for HLHS. However, there is hope in emerging research studies and clinical trials, according to Dr. Nelson, who says it’s understandable that people are looking to stem cells for hope. “It becomes much more real when you have a personal connection to a disease or illness where we don’t have good options.”

Watch this blog for updates on clinical trials as they become available.

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Genetic Investigations into HLHS: Part 1


Often times, especially for mothers, we find a way to blame ourselves for things that happen to our children. When a family receives the news that their child has HLHS, they begin thinking about what could have caused it. How could this possibly have happened?  

While the exact cause of HLHS is not known at this time, researchers hope to answer that very question. Discovering the genetic basis for HLHS is the key focus area for Dr. Timothy Olson, a pediatric cardiologist with a research focus in cardiovascular genetics, and his colleagues within the Todd and Karen Wanek Family Program for HLHS at Mayo Clinic

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Can a half of a heart become whole?


An article published on November 6, 2012, in the Journal of the American College of Cardiology documented that cardiac surgeons, in collaboration with cardiologists, at Boston Children’s Hospital have successfully “recruited” the left ventricle, (the chamber of the heart that is affected by HLHS) in 12 individuals with HLHS by using a surgical procedure referred to as Staged Left Ventricle Recruitment (SLVR.)

“Children have an enormous growth and healing potential,” Dr. Emani, lead author of  Staged Left Ventricular Recruitment After Single-Ventricle Palliation in Patients With Borderline Left Heart Hypoplasia, explained. “We realized that rather than give up on the left ventricle and commit a child to single ventricle circulation for life, we could leverage that growth potential in a staged approach that would promote growth in the left ventricle and gradually recruit it back into operation.”

Echocardiogram images of heart

Echocardiogram of Representative Patient Who Underwent Staged LV Recruitment. The LV is endocardial fibroelastosis–bound and nonapex forming (A) before stage 1 but apex forming and normal in size (B) before biventricular conversion.

As stated in the article, this approach was successful in individuals with borderline hypoplasia. Because most babies with HLHS have slit-like left ventricles and aortic and/or mitral valve atresia, this approach may not be an option in a majority of cases.  If you have questions about SLVR, speak with your pediatric cardiologist or primary cardiac care provider.  Read the full article at ScienceDirect.com

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