A Way to Get Stem Cells to Make Living Heart Valve Tissue?

What a benefit it would be to be able to replace diseased and defective heart valves with new heart valves. Thus, living tissue engineered heart valves (TEHV) would be a boon to children who require replacement heart valves that have the capacity to grow with the child and completely integrate into the child’s heart tissue. A persistent challenge for TEHV is accessible human cell source(s) that have the ability to mimic native valve cell phenotypes and possess matrix remodeling characteristics that are essential for long-term function.

Mesenchymal stem cells derived from bone marrow (BMMSC) or adipose tissue (ADMSC) are intriguing cell sources for TEHV. Unfortunately, they have not been compared to pediatric human aortic valve interstitial cells (pHAVIC) in relevant 3-dimensional culture environments.

In a recent study, Bin Duan from the Biomedical Engineering department at Cornell University compared the spontaneous and induced multipotency of ADMSC and BMMSC to that of pHAVIC using different induction culture systems within three-dimensional (3D) bioactive hybrid hydrogels that have similar material properties to those of aortic heart valve leaflets. pHAVICs possessed some multi-lineage differentiation capacity in response to induction media, but these cells were limited to the earliest stages and their differentiation capacity were less potent than either ADMSCs or BMMSCs. ADMSCs expressed cell phenotype markers that were similar to pHAVICs when they were grown in HAVIC growth media spiked with a growth factor called basic fibroblast growth factor (bFGF). BMMSCs generally expressed extra cellular matrix remodeling characteristics similar to pHAVICs.

Duan and his colleagues then chemically attached bFGF to components of the 3D hybrid hydrogels in order to further immobilize them. The immobilized bFGF upregulated vimentin expression and promoted the fibroblastic differentiation of pHAVIC, ADMSC and BMMSC. Since fibroblasts help make heart valves, these changes in gene expression might presage the ability of these cells to form new heart living heart valve tissue.

Thus, these findings show that even though mesenchymal stem cells retain a heightened capacity to form bone in 3D culture, this tendency can be shifted fibroblast cell fates by tethering bFGF to the 3-D matrix. Such a strategy is probably rather important for utilizing stem cell sources in heart valve tissue engineering applications.

This is an important finding.  Even though the production of TEHVs are some ways off, Duan’s findings might provide a strategy to begin cells on the path to making TEHVs.

Skin Cells Can Be Engineered into Pulmonary Valves for Pediatric Patients

Stem cells researchers from the University of Maryland School of Medicine in Baltimore have designed a treatment that takes a child’s skin cells, reprograms them to function as heart valvular cells and then utilizes these cells to engineer a pulmonary valve that can grow with the patient.

“Current valve replacements cannot grow with patients as they age, but the use of a patient-specific pulmonary valve would introduce a ‘living’ valvular construct that should grow with the patient. Our study is particularly important for pediatric patients who often require repeated operations for pulmonary valve replacements,” said lead author David L. Simpson, Ph.D., The study is published in the current issue of Annals of Thoracic Surgery.

In the heart, the “pulmonary valve” is located between the right ventricle and the pulmonary artery, which takes blood from the right side of the heart to the lungs. This crescent-shaped valve aids in moving blood from the heart into the lungs.

Pulmonary valve

According to data from the Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database, close to 800 patients experience pulmonary valve failure and could benefit from bioengineered patient-specific pulmonary valves. The STS Database collects information from more than 95% of hospitals in the United States and Canada that perform pediatric and congenital heart surgery. Numbers compiled from these hospitals show that approximately 3,200 patients underwent pulmonary valve replacement during a four-year period from January 2010 to December 2013.

Although the study was conducted outside the body, the next step will be implanting the new valves into patients to test their durability and longevity.

“We created a pulmonary valve that is unique to the individual patient and contains living cells from that patient. That valve is less likely to be destroyed by the patient’s immune system, thus improving the outcome and hopefully increasing the quality of life for our patient,” said senior co-author Sunjay Kaushal, M.D., Ph.D.. “In the future, it may be possible to generate this pulmonary valve by using a blood sample instead of a skin biopsy.”

David Simpson added that he hopes the study will encourage additional research in tissue engineering and entice more people to enter the field, “Hopefully, growing interest and research in this field will translate more quickly into clinical application.”