Novel Application Method for Mesenchymal Stem Cell Therapy Utilizing Its Attractant-Responsive Accumulation Property

Nobuyuki Ueda,Takayoshi Yamaza,Akihiro Furuhashi,Ikiru Atsuta,Kiyoshi Koyano,Ryosuke Kondo,Yasunori Ayukawa,Yuri Matsuura,Yu Watanabe,Ikue Narimatsu,Xiaoxu Zhang

doi:10.3390/app9224908

Nobuyuki Ueda, Takayoshi Yamaza + Show 9 more

Open Access

https://doi.org/10.3390/app9224908

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Journal: Applied Sciences	Publication Date: Nov 15, 2019
Citations: 7	License type: CC BY 4.0

Affiliation: Kyushu University

Abstract

Stem cell therapy is an emerging treatment modality for various diseases. Because mesenchymal stem cells (MSCs) are known to accumulate at the site of damage, their possible clinical application has been investigated. MSCs are usually administered using intravenous injection, but this route carries a risk of pulmonary embolism. In contrast, topical injection of MSCs reportedly has an inferior therapeutic effect. We developed a remote administration method that uses collagen gel as a scaffold and investigated the effect of this scaffold on the retention of stemness, homing ability, and therapeutic effect using a mouse tooth extraction model. After verifying the retention of stemness of MSCs isolated from the bone marrow of donor mice in the scaffold, we administered MSCs subcutaneously into the back of the recipient mice with scaffold and observed the accumulation and the acceleration of healing of the extraction socket of the maxillary first molar. The MSCs cultured with scaffold retained stemness, the MSCs injected into back skin with scaffold successfully accumulated around the extraction socket, and socket healing was significantly enhanced. In conclusion, administration of MSCs with collagen scaffold at a remote site enhanced the lesion healing without the drawbacks of currently used administration methods.

Highlights

Mesenchymal stem cells (MSCs), which are known to contribute to tissue regeneration and repair [1] are normally present in a dormant state in almost all organs [2]
Cells were washed with phosphate-buffered saline (PBS) and cultured in growth medium comprising alpha-minimum essential medium (α-MEM; Invitrogen, Grand Island, NY, USA) supplemented with 20% fetal bovine serum (FBS; Equitech-Bio, Kerrville, TX, USA), 2 mM L-glutamine (Invitrogen), 100 U/mL penicillin (Invitrogen), and 100 μg/mL
The number of MSCson other remaining in the scaffold days was significantly decreased compared the number remaining the scaffold

Summary

Introduction

Mesenchymal stem cells (MSCs), which are known to contribute to tissue regeneration and repair [1] are normally present in a dormant state in almost all organs [2]. Upon the release of cytokines by a stimulus such as inflammation or tissue injury, MSCs begin to proliferate and migrate. Sci. 2019, 9, 4908 to where cytokines are being released [3]. MSC administration routes include intra-arterial/intravenous, intraperitoneal, and direct administration into tissues and organs. These methods can roughly be classified into two groups: systemic administration and local administration. Fewer than 10% of administered MSCs accumulate at the site of damage, with many cells becoming captured in the lungs [7,8,9,10]

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