Research Paper|Volume 13, Issue 1|pp 1132—1152

Ginsenoside RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells on radiation induced intestinal injury

Yujun Luo^1,³, Beibei Wang^2,³, Jianhua Liu⁴, Faxin Ma^1,⁵, Dongling Luo^1,⁶, Zhongwen Zheng³, Quan Lu^1,³, Weijie Zhou³, Yue Zheng³, Chen Zhang^2,³, Qiyi Wang^1,³, Weihong Sha^2,³, Hao Chen^2,³

¹Shantou University Medical College, Shantou 515041, Guangdong, P.R. China
²The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, Guangdong, P.R. China
³Department of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P.R. China
⁴Department of Oncology, Cancer Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P.R. China
⁵Department of Gastroenterology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, Guangdong, P.R. China
⁶Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, P.R. China

* Equal contribution

Received: June 15, 2020Accepted: October 20, 2020Published: December 3, 2020

https://doi.org/10.18632/aging.202241

Copyright: © 2020 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII).

Method: Irradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA.

Result: RG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6.

Conclusion: Our study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.