Preferred M2 Polarization by ASC-Based Hydrogel Accelerated Angiogenesis and Myogenesis in Volumetric Muscle Loss Rats.

Hong Huang,Deyun Chen,Ling Zhizhong,Haojie Hao,Jiejie Liu,Rong Xiang,Xiaobing Fu,Haijing Song,Meirong Li,Weidong Han,Chaoguang Jiang

doi:10.1155/2017/2896874

Abstract

Volumetric muscle loss (VML) injury resulted from massive muscle defects and diseases for which there are still no effective therapeutic treatments. This study aimed to investigate the effects of rat adipose-derived mesenchymal stem cells (rASCs) and rASCs-conditioned medium- (CM-) based type I collagen hydrogel on macrophage (MP) transition, myogenesis, and vascularization in the rat VML model. Laser Doppler results demonstrated much higher blood flow in the rASC- and CM-based hydrogel groups. qRT-PCR, hematoxylin and eosin, immunofluorescence, and Sirius Red staining manifested that both rASCs and CM-based hydrogel implantation accelerated muscle repair with upregulated angiogenesis and myogenesis, attenuated inflammation while facilitating M2 transition, and decreased the collagen deposition compared with the hydrogel group. In vitro experiments indicated that factors secreted from polarized M2 MPs could accelerate the migration and tube formation capacities of HUVECs. These results suggested that rASCs exerted immunomodulatory effects on MPs which further enhanced the proangiogenic potential on ECs to promote myogenesis and angiogenesis during muscle repair. These fundamental results support further clinical applications of ASCs for muscle loss injury.

Highlights

Volumetric muscle loss (VML) is an injury that results from traumatic or surgical actions, which lead to loss of muscle mass and deprivation of function [1]
The results provided the basis of rat adipose-derived mesenchymal stem cells (rASCs)-based hydrogel therapy in the VML injury
We showed that rASC- or rASC-conditioned medium- (CM-)based hydrogel filled the defected tibialis anterior (TA) muscle and displayed effective myogenesis, improved blood perfusion, and decreased excessive collagen deposition compared with the hydrogel-alone group

Summary

Introduction

Volumetric muscle loss (VML) is an injury that results from traumatic or surgical actions, which lead to loss of muscle mass and deprivation of function [1]. The underlying mechanisms among ASC-based type I collagen hydrogel, MP polarization, angiogenesis, and fibrosis remain to be elucidated in the VML injury model. Together with these properties, we exogenously implanted rASCs- and its conditioned medium- (CM-) based collagen hydrogel to a rat tibialis anterior (TA) VML model. We exogenously implanted rASCs- and its conditioned medium- (CM-) based collagen hydrogel to a rat tibialis anterior (TA) VML model We observed that both rASCs- and CM-based hydrogel promoted myogenesis, decreased adipose tissue formation, and significantly promoted vascularization. The results provided the basis of rASCs-based hydrogel therapy in the VML injury

Materials and Methods

Results

Discussion

Findings

Conclusions