Innovations in Heart Transplantation: The Role of Gene Therapy and Tissue Engineering

July 28, 2025 Ashley Chuong

Ashley Chuong

Background:  End-stage heart failure is an advanced heart disease characterized by a high mortality rate and no improvement with medical interventions. Heart transplants, the surgical replacement of native heart with a donor, are the gold-standard treatment used to treat end-stage heart failure.1 A major limitation of heart transplants is a lack of abundant donors, leading to a 67.8% 1-year mortality rate on the heart transplant waitlist.2 Additionally, only about 30-40% of donor hearts are used due to histocompatibility or size.3 Current innovations in improving the availability of donor hearts include modifying the allocation system, novel preservation systems, and low-level antibody matching.3 Thus, regenerative medicine, such as gene therapy and tissue engineering, is being evaluated as an adjunct or alternative to current heart transplantation methods.4

Methods: The literature search was conducted on the PubMed online database using key words “heart failure”, “heart transplant”, “gene therapy”, and “tissue engineering”.

Results: Gene therapy is a discipline that aims to insert, remove, or correct any mutated genes, often through the use of edited genetic material that can be delivered to target cells.5 The genetic modification of cardiomyocytes is difficult due to mechanical force, immune challenges, and endothelial barriers.6 Currently, researchers are utilizing gene therapy on ex-vivo hearts in preservation systems to decrease ischemic reperfusion injury and to improve rejection rates.7 Similarly, tissue engineering is a discipline that combines materials engineering and cellular science to create complex tissues and organs.8 For heart transplants, researchers have focused on making cardiac muscle from stem cells to be used as grafts and culturing new cells on decellularized heart tissue. These technologies have yet to be used in human subjects and are being used in rat and swine models.9,10

Conclusions: Regenerative medicine proves to be a burgeoning field that has the potential to enhance how we treat heart failure by enhancing the donor pool and increasing the efficacy of current methods of heart transplantation. Additionally, gene therapy and tissue engineering could redefine how we treat heart failure in the future. The major challenges are going to be ensuring immune compatibility and reproducibility as these technologies are further developed.

Work Cited

  1. Mangini S, Alves BR, Silvestre OM, et al. Heart transplantation: review. Einstein (Sao Paulo). Apr-Jun 2015;13(2):310-8. doi:10.1590/s1679-45082015rw3154
  2. Bakhtiyar SS, Godfrey EL, Ahmed S, et al. Survival on the Heart Transplant Waiting List. JAMA Cardiology. 2020;5(11):1227-1235. doi:10.1001/jamacardio.2020.2795
  3. Coniglio AC, Patel CB, Kittleson M, Schlendorf K, Schroder JN, DeVore AD. Innovations in Heart Transplantation: A Review. Journal of Cardiac Failure. 2022;28(3):467-476. doi:10.1016/j.cardfail.2021.10.011
  4. Goto T, Nakamura Y, Ito Y, Miyagawa S. Regenerative medicine in cardiovascular disease. Regenerative Therapy. 2024/06/01/ 2024;26:859-866. doi:https://doi.org/10.1016/j.reth.2024.09.004
  5. Sayed N, Allawadhi P, Khurana A, et al. Gene therapy: Comprehensive overview and therapeutic applications. Life Sciences. 2022/04/01/ 2022;294:120375. doi:https://doi.org/10.1016/j.lfs.2022.120375
  6. Bowles DE, Mendiola Pla M, Chiang Y, Roan J-N. Gene Therapy for Cardiac Transplantation. In: Fukushima N, ed. Heart Transplantation – New Insights in Therapeutic Strategies. IntechOpen; 2022.
  7. Vervoorn MT, Amelink J, Ballan EM, et al. Gene therapy during ex situ heart perfusion: a new frontier in cardiac regenerative medicine? Front Cardiovasc Med. 2023;10:1264449. doi:10.3389/fcvm.2023.1264449
  8. Eschenhagen T, Weinberger F. Challenges and perspectives of heart repair with pluripotent stem cell-derived cardiomyocytes. Nature Cardiovascular Research. 2024/05/01 2024;3(5):515-524. doi:10.1038/s44161-024-00472-6
  9. Jebran A-F, Seidler T, Tiburcy M, et al. Engineered heart muscle allografts for heart repair in primates and humans. Nature. 2025/03/01 2025;639(8054):503-511. doi:10.1038/s41586-024-08463-0
  10. Taylor DA, Frazier OH, Elgalad A, Hochman-Mendez C, Sampaio LC. Building a Total Bioartificial Heart: Harnessing Nature to Overcome the Current Hurdles. Artificial Organs. 2018;42(10):970-982. doi:https://doi.org/10.1111/aor.13336

 

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