DAMP-modulating nanoparticle for successful pancreatic islet and stem cell transplantation

Soo Bin Jang; Sang-Man Jin; Hyung Shik Kim; Yong Yeon Jeong; Sang Jun Lee; Soojung Hahn; Hyemin Lee; Han Sin Lee; Jae Hyeon Kim; Dong Yun Lee

doi:10.1016/j.biomaterials.2022.121679

DAMP-modulating nanoparticle for successful pancreatic islet and stem cell transplantation

Biomaterials. 2022 Aug:287:121679. doi: 10.1016/j.biomaterials.2022.121679. Epub 2022 Jul 12.

Authors

Affiliations

¹ Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 04763, Republic of Korea.
² Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea.
³ Department of Radiology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, 58128, Republic of Korea.
⁴ Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06355, Republic of Korea.
⁵ Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, 06355, Republic of Korea. Electronic address: jaehyeon@skku.edu.
⁶ Department of Bioengineering, College of Engineering, Hanyang University, Seoul, 04763, Republic of Korea; Institute of Nano Science & Technology (INST) & Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, 04763, Republic of Korea; Elixir Pharmatech Inc., Seoul, 04763, Republic of Korea. Electronic address: dongyunlee@hanyang.ac.kr.

PMID: 35849998
DOI: 10.1016/j.biomaterials.2022.121679

Abstract

Cell therapy is targeted at many organs, but locally or systemically delivered cells are shortly able to survive resulting from the immune/inflammation reactions and irregular cell targeting. Here we explore the multimodal nanoparticle having anti-inflammation and magnetic guidance for successful cell transplantation. We design magnetic resonance (MR)-active glycyrrhizin-chitosan coated superparamagnetic iron oxide nanoparticle (SPIO@Chitosan-GL) to inhibit release of inflammatory damage-associated molecular pattern (DAMP) protein and to offer noninvasive monitoring after intrahepatic transplantation of pancreatic islets and mesenchymal stem cell (MSC) spheroids. Intracellular delivered SPIO@Chitosan-GL is not cytotoxic to pancreatic islets and MSC spheroids and attenuate DAMP release from them. Also, therapeutic cells labeled with SPIO@Chitosan-GL are magnetically localized to the intended lobe of liver during transplantation procedure. If necessary, partial hepatectomy can be performed to remove the localized therapeutic cells for protection of the remaining liver lobes from systemic inflammation. Therapeutically, the cells selectively localized in the liver can treat blood glucose in diabetic mice to normal levels with DAMP modulation, and are visualized using in vivo MR imaging for over 4 weeks. Collectively, DAMP-modulating SPIO@Chitosan-GL can be used in multimodal nanomedince for attenuating the inflammation reaction by transplanted cells and for noninvasively long-term monitoring of transplanted cells.

Keywords: Damage-associated molecular pattern (DAMP); Glycyrrhizin-chitosan conjugate; Inflammatory reaction; Magnetically guided transplantation; Superparamagnetic iron oxide nanoparticle.