Long-term drug modification to the surface of mesenchymal stem cells by the avidin-biotin complex method

Abstract

Mesenchymal stem cells (MSCs) have various functions, making a significant contribution to tissue repair. On the other hand, the viability and function of MSCs are not lasting after an in vivo transplant, and the therapeutic effects of MSCs are limited. Although various chemical modification methods have been applied to MSCs to improve their viability and function, most of conventional drug modification methods are short-term and unstable and cause cytotoxicity. In this study, we developed a method for long-term drug modification to C3H10T1/2 cells, murine mesenchymal stem cells, without any damage, using the avidin-biotin complex method (ABC method). The modification of NanoLuc luciferase (Nluc), a reporter protein, to C3H10T1/2 cells by the ABC method lasted for at least 14 days in vitro without major effects on the cellular characteristics (cell viability, cell proliferation, migration ability, and differentiation ability). Moreover, in vivo, the surface Nluc modification to C3H10T1/2 cells by the ABC method lasted for at least 7 days. Therefore, these results indicate that the ABC method may be useful for long-term surface modification of drugs and for effective MSC-based therapy.

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

“…It has been reported that most MSCs disappear from the body by undergoing necrotic cell death within one week of administration [63,64], in which shear stress, lack of nutrients, hypoxia, and detachment-induced apoptosis have been observed [63,65]. Although MSCs can generally escape T cell and natural killer (NK) cell-mediated destruction, MSCs may be phagocytosed by monocytes or macrophages, because some studies demonstrated that MSCs were phagocytosed by monocytes/macrophages under in vitro culture conditions [66,67].This rapid disappearance could avoid unexpected adverse effects attributed to MSCs and may be beneficial to establish the safety of MSCs as a drug delivery vehicle.…”

“…Although endogenous MSCs may act as pro-tumorigenic cells, MSC administration might minimally impact tumor growth. While induction from MSCs to CAFs required 4-30 days [73][74][75], most MSCs disappeared from the body within a week [63,64]. In addition, the differentiation of MSCs increased the expression of MHC molecules [21], which could result in immune rejection.…”

Click Chemistry as a Tool for Cell Engineering and Drug Delivery

“…It is important to understand the biodistribution and biological fate of transplanted cells in order to develop a therapeutic strategy for cell-based therapies. Cell tracking techniques provide information about the in vivo behavior of transplanted cells, including migration, translocation, proliferation, cell death, and differentiation [51,52,53]. Researchers have also attempted to develop a cell tracking method.…”

“…Furthermore, the cell tracking method involves a short reaction time and label cells with high efficacy. However, the detectable duration of this method is limited because of the instability of the labels [51,64]. In addition, imageable probes such as lipophilic dyes and radiotracers often cause cytotoxicity [50,64].…”

Stable Surface Modification of Mesenchymal Stem Cells Using the Avidin‐Biotin Complex Technique

“…Avidin and derivatives such as streptavidin form one of the strongest non‐covalent bonds with biotin; the binding method using these compounds is generally known as the avidin‐biotin complex (ABC) technique (Diamandis & Christopoulos, ). Because bond formation is extremely specific, stable, and rapid, the ABC technique has great potential to overcome the disadvantages of conventional cell surface modification methods (Takayama et al., ). This unit describes ABC‐mediated cell surface modification of MSCs and the in vitro and in vivo evaluation of the modified MSCs.…”