Delivery of MSCs with a Hybrid β-Sheet Peptide Hydrogel Consisting IGF-1C Domain and D-Form Peptide for Acute Kidney Injury Therapy
Received 30 March 2020
Accepted for publication 9 June 2020
Published 17 June 2020 Volume 2020:15 Pages 4311—4324
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Linlin Sun
Hongfeng Wang,1,* Yuna Shang,2,* Xiaoniao Chen,3 Zhongyan Wang,2 Dashuai Zhu,4 Yue Liu,4 Chuyue Zhang,1 Pu Chen,1 Jie Wu,1 Lingling Wu,1 Deling Kong,2 Zhimou Yang,2 Zongjin Li,4 Xiangmei Chen1
1Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing 100039, People’s Republic of China; 2State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin 300071, People’s Republic of China; 3Department of Ophthalmology, Chinese PLA General Hospital, Beijing 100039, People’s Republic of China; 4Department of Pathophysiology, Nankai University School of Medicine, Tianjin, 300071, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiangmei Chen
Chinese PLA General Hospital, Beijing 100039, People’s Republic of China
Nankai University, Tianjin 300071, People’s Republic of China
Purpose: By providing a stem cell microenvironment with particular bioactive constituents in vivo, synthetic biomaterials have been progressively successful in stem cell-based tissue regeneration by enhancing the engraftment and survival of transplanted cells. Designs with bioactive motifs to influence cell behavior and with D-form amino acids to modulate scaffold stability may be critical for the development and optimization of self-assembling biomimetic hydrogel scaffolds for stem cell therapy.
Materials and Methods: In this study, we linked naphthalene (Nap) covalently to a short D-form peptide (Nap-DFDFG) and the C domain of insulin-like growth factor-1 (IGF-1C) as a functional hydrogel-based scaffolds, and we hypothesized that this hydrogel could enhance the therapeutic efficiency of human placenta-derived mesenchymal stem cells (hP-MSCs) in a murine acute kidney injury (AKI) model.
Results: The self-assembling peptide was constrained into a classical β-sheet structure and showed hydrogel properties. Our results revealed that this hydrogel exhibited increased affinity for IGF-1 receptor. Furthermore, cotransplantation of the β-IGF-1C hydrogel and hP-MSCs contributed to endogenous regeneration post-injury and boosted angiogenesis in a murine AKI model, leading to recovery of renal function.
Conclusion: This hydrogel could provide a favorable niche for hP-MSCs and thereby rescue renal function in an AKI model by promoting cell survival and angiogenesis. In conclusion, by covalently linking the desired functional groups to D-form peptides to create functional hydrogels, self-assembling β-sheet peptide hydrogels may serve as a promising platform for tissue-engineering and stem cell therapy.
Keywords: self-assembly, β-sheet, hydrogel, D-form peptide, C domain of insulin-like growth factor, IGF-1C, mesenchymal stem cells, MSCs, acute kidney injure, AKI
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