Dr. Jinah Jang of POSTECH in Kyungbuk, Korea and colleagues provide a review, published in APL Bioengineering, of various types of candidate stem cells with cardiac regenerative potential (e.g., and pluripotent stem cells), and examples of their applications and limitations.
The review also provides an update on 3D bioprinting approaches to fabricate cardiac patches, highlighting strategies to implement vascularization and augment cardiac functional properties.
Key points of the review include:
- Multiple stem cell types have been suggested as candidates for cardiomyocytes regeneration; however, there is no gold standard on the specific cell type to be used for cardiac repair.
- Given the complexity of the myocardial tissue that accommodates diverse cell types, the regeneration process requires coordination of varied cell types with synergistic effects, along with a suitable extracellular matrix microenvironment.
- Advances in bioengineering approaches such as 3D bioprinting, along with a potentially powerful autologous cell source (hiPSC-CMs), offer a new option for resuscitating injured cardiomyocytes and vasculatures, and may provide new insights into the pathogenesis of cardiovascular diseases.
- Despite promising preclinical results, these approaches are still in their infancy. Challenges include the need for rapid vascularization; improving the functional and mechanical properties of the engineered cardiac patch; ensuring perfusion by host's coronary circulation; and achieving enhanced integration with host tissue.
Dr. John Wikswo, Founding Director, Vanderbilt Institute for Integrative Biosystems Research and Education and Professor of Biomedical Engineering, Molecular Physiology and Biophysics, and Physics at Vanderbilt University in Nashville, commented by phone.
"The immediate value of this work, as the authors state, is that it will 'open new avenues for cardiac research,'" he said. "Understanding the role of the medium-term secretion of paracrine factors and extracellular vesicles by the implanted cells is very important, and developing the microvasculature to keep the implanted cells alive is critical."
"In the near term, I expect that is work may provide an important step in figuring out how to deliver those factors without using cells," he continued. "Biotic patches could inform abiotic ones. Abiotic patches or injectables may not need to be tailored to an individual patent, and can be stored after manufacture, rather than having to be created by expanding the patient's own cells."
"The challenges to clinical implementation are delineated multiple times throughout the paper, and some of these problems are huge and should not be underestimated," he said. "There are two types of challenges: the production of the patch, and its proper, functional integration with the heart."
"The authors do an excellent job of addressing the first, and discuss the second - i.e., it is important to provide an age-matched phenotype, proper excitation-contraction coupling, a positive force-frequency relationship, efficient energy conversion, properly matched conduction velocity and tissue anisotropy, absence of spontaneous beating yet responsiveness to local activation, and such."
"The progress to date on 3D-printed cardiac patches is impressive, and should provide a strong foundation for near-future research and far-future clinical applications," Dr. Wikswo concluded.
Dr. Noelle Comolli, Associate Professor and Chair, Chemical and Biological Engineering at Villanova University, commented by email to Reuters Health, "It's a good review, well laid out and honest on the drawbacks."
"Major concerns with this type of patch are the cells themselves," she said, including ethical concerns with the pluripotent sourcing, and the fact that "iPSCs and multipotent stem cells are more common now, but still do not survive long after implant without an external matrix. Several studies have shown arrhythmia or other issues upon implant. So, the cells themselves still need to be better understood."
"3D printing of the polymer matrix with cells allows us to design an artificial extra cellular matrix (ECM). This allows the transplanted cells to remain in the tissue and increases the chances of their survival," she noted. "Many of these designs are biodegradable so that as the cells produce their own ECM, the polymer one disappears. The timing of this degradation will be critical in the patch success."
"Overall, I think it's an exciting technology- but still a few years away from clinic," Dr. Comolli concluded.
Dr. Jang did not respond to requests for a comment.
SOURCE: https://bit.ly/3ChLFGv APL Bioengineering, online July 27, 2021.
By Marilynn Larkin
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