Transplantation of Stem Cell Spheroid-Laden 3-Dimensional Patches with Bioadhesives for the Treatment of Myocardial Infarction

Author:

Jeon Hye Ran1,Kang Jeon Il2,Bhang Suk Ho3,Park Kyung Min24ORCID,Kim Dong-Ik15

Affiliation:

1. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul 06355, Republic of Korea.

2. Department of Bioengineering and Nano-Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea.

3. School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

4. Research Center for Bio Materials & Process Development, Incheon National University, 119 Academy-ro, Yeonsu-gu, Incheon 22012, Republic of Korea.

5. Division of Vascular Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea.

Abstract

Myocardial infarction (MI) is treated with stem cell transplantation using various biomaterials and methods, such as stem cell/spheroid injections, cell sheets, and cardiac patches. However, current treatment methods have some limitations, including low stem cell engraftment and poor therapeutic effects. Furthermore, these methods cause secondary damage to heart due to injection and suturing to immobilize them in the heart, inducing side effects. In this study, we developed stem cell spheroid-laden 3-dimensional (3D) patches (S_3DP) with biosealant to treat MI. This 3D patch has dual modules, such as open pockets to directly deliver the spheroids with their paracrine effects and closed pockets to improve the engraft rate by protecting the spheroid from harsh microenvironments. The spheroids formed within S_3DP showed increased viability and expression of angiogenic factors compared to 2-dimensional cultured cells. We also fabricated gelatin-based tissue adhesive biosealants via a thiol-ene reaction and disulfide bond formation. This biosealant showed stronger tissue adhesiveness than commercial fibrin glue. Furthermore, we successfully applied S_3DP using a biosealant in a rat MI model without suturing in vivo, thereby improving cardiac function and reducing heart fibrosis. In summary, S_3DP and biosealant have excellent potential as advanced stem cell therapies with a sutureless approach to MI treatment.

Funder

Ministry of Trade, Industry and Energy

Ministry of Science and ICT, South Korea

Korea Fund for Regenerative Medicine

Korea government

Publisher

American Association for the Advancement of Science (AAAS)

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