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将可注射水凝胶与生长因子控释相结合的高效细胞移植

Efficient cell transplantation combining injectable hydrogels with control release of growth factors.

作者信息

Mitsui Ryo, Matsukawa Makoto, Nakagawa Kiyoko, Isomura Emiko, Kuwahara Toshie, Nii Teruki, Tanaka Susumu, Tabata Yasuhiko

机构信息

First Department of Oral and Maxillofacial Surgery, Osaka University, Graduate School of Dentistry, 1-8, Yamadaoka, Suita, Osaka, 565-0871, Japan.

Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, 53 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.

出版信息

Regen Ther. 2021 Sep 25;18:372-383. doi: 10.1016/j.reth.2021.09.003. eCollection 2021 Dec.

Abstract

INTRODUCTION

The objective of this study is to investigate the effect of gelatin microspheres incorporating growth factors on the therapeutic efficacy in cell transplantation. The strength of this study is to combine gelatin hydrogel microspheres incorporating basic fibroblast growth factor and platelet growth factor mixture (GM/GF) with bioabsorbable injectable hydrogels (iGel) for transplantation of adipose-derived stem cells (ASCs).

METHODS

The rats ASCs suspended in various solutions were transplanted in masseter muscle. Rats were euthanized 2, 7, 14 days after injection for measurement of the number of ASCs retention in the muscle and morphological evaluation of muscle fibers and the inflammation of the injected tissue by histologic and immunofluorescent stain.

RESULTS

Following the injection into the skeletal muscle, the GM/GF allowed the growth factors to release at the injection site over one week. When ASCs were transplanted into skeletal muscle using iGel incorporating GM/GF (iGel+GM/GF), the number of cells grafted was significantly high compared with other control groups. Moreover, for the groups to which GM/GF was added, the cells transplanted survived, and the Myo-D expression of a myoblast marker was observed at the region of cells transplanted.

CONCLUSIONS

The growth factors released for a long time likely enhance the proliferative and differentiative capacity of cells. The simple combination with iGel and GM/GF allowed ASCs to enhance their survival at the injected site and consequently achieve improved therapeutic efficacy in cell transplantation.

摘要

引言

本研究的目的是探讨包裹生长因子的明胶微球对细胞移植治疗效果的影响。本研究的优势在于将包裹碱性成纤维细胞生长因子和血小板生长因子混合物的明胶水凝胶微球(GM/GF)与可生物吸收的注射用水凝胶(iGel)相结合,用于脂肪来源干细胞(ASC)的移植。

方法

将悬浮于不同溶液中的大鼠ASC大量移植到咬肌中。在注射后2、7、14天对大鼠实施安乐死,通过组织学和免疫荧光染色测量肌肉中ASC保留的数量,并对肌纤维和注射组织的炎症进行形态学评估。

结果

注射到骨骼肌后,GM/GF使生长因子在注射部位释放超过一周。当使用含有GM/GF的iGel(iGel+GM/GF)将ASC移植到骨骼肌中时,与其他对照组相比,移植的细胞数量显著增多。此外,对于添加了GM/GF的组,移植的细胞存活,并且在移植细胞区域观察到成肌细胞标志物Myo-D的表达。

结论

长时间释放的生长因子可能增强细胞的增殖和分化能力。iGel与GM/GF的简单组合使ASC在注射部位提高了存活率,从而在细胞移植中实现了更好的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c32/8479297/4b9c516718b7/gr1.jpg

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