Modification of human MSC surface with oligopeptide‐PEG‐lipids for selective binding to activated endothelium

Abstract

Promising cell therapies using mesenchymal stem cells (MSCs) is proposed for stroke patients. Therefore, we aimed to efficiently accumulate human MSC (hMSC) to damaged brain area to improve the therapeutic effect using poly(ethylene glycol) (PEG)‐conjugated phospholipid (PEG‐lipid) carrying an oligopeptide as a ligand, specific for E‐selectin which is upregulated on activated endothelial cells under hypoxia‐like stroke. Here we synthesized E‐selectin‐binding oligopeptide (ES‐bp) conjugated with PEG spacer having different molecular weights from 1 to 40 kDa. We found that ES‐bp can be immobilized onto the hMSC surface through PEG‐lipid without influence on cell growth and differentiation into adipocytes and osteocytes, respectively. It is also possible to control the immobilization of ES‐bp on hMSC surface (<108 ES‐bp per cell). Immobilized ES‐bp can be continuously immobilized at the outside of cell membrane when PEG‐lipids with PEG 5 and 40 kDa were used. In addition, the modified hMSC can specifically attach onto E‐selectin‐immobilized surface as a model surface of activated endothelium in human blood, indicating the sufficient number of immobilized ES‐bp onto hMSC. Thus, this technique is one of the candidates for hMSC accumulation to cerebral infarction area. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1779–1792, 2019.

Challenges and Improvements of Novel Therapies for Ischemic Stroke

“… Zhang et al (2019) designed fabrication of magnetosome-like 1D ferrimagnetic iron oxide nanochains (MFIONs) which increased the MSCs delivery efficiency to 2-3 folds and decreased the mortality of stroke. Other researchers tried using poly (ethylene glycol) (PEG)–conjugated phospholipid (PEG-lipid) as a ligand and conjugated with E-selectin-binding oligopeptide (ES-bp) which improved the cell attachment in active endothelium cells in the damage area ( Noiri et al, 2019 ). Others used a PEG microsphere to encapsulate NSCs and suspended these microspheres in the extracellular matrix (ECM) hydrogel, then injected the modified cells into mice, this ECM hydrogel delivered NSCs to the infarct area 5-fold than the control group ( Ghuman et al, 2021 ).…”

Enhancement of intercellular interaction between iPSC-derived neural progenitor cells and activated endothelial cells using cell surface modification with functional oligopeptides

“…No significant difference was observed in the binding of the two molecules with rE-selectin. 27 As a result, we chose to use a C-terminal oligopeptide in this study.…”

“…First, the rE-selectin-immobilized surface was used as a model surface of activated endothelial cells 27 with the upregulation of this marker. rE-selectin is a conjugate of the Fc domain of IgG with the functional domain of E-selectin.…”

“…[23][24][25] Our group has previously reported that cell surface modification with regulators could assist in preventing thromboinflammation in human whole blood and in vivo animal experiments. 26 In addition, cell surface modification with oligopeptide and oligoDNA could help specific cell attachment, [27][28][29][30] which would serve to realize a high accumulation of cells in the infarcted brain area. However, there is little progress in our understanding of the mechanism of MSC function in stroke therapeutics.…”

“…[23][24][25] The oligopeptide we used here is an E-selectin binding peptide (Esbp: DITWDQLWDLMKGGGC) and a scrambled peptide for control experiments [Esbp-sc: DQWIMDLTDLKWGGGC]. 27,36 We studied the surface modification of miPSC-derived NPCs and the interaction of the modified NPCs with surface-immobilized recombinant E-selectin. Additionally, we monitored the modified cells over a period of 7 days to determine whether there was any change in gene expression in the cells or in their viability.…”