AUTHOR=Guo Qi , Chang Yajie , Li Jingjie , Zhou Chuanchuan , Huang Rui , Yang Xing , Liu Guihua , Liang Xiaoyan TITLE=Regenerative Effects of Locally or Intra-Arterially Administered BMSCs on the Thin Endometrium JOURNAL=Frontiers in Bioengineering and Biotechnology VOLUME=Volume 10 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2022.735465 DOI=10.3389/fbioe.2022.735465 ISSN=2296-4185 ABSTRACT=Stem cell-based therapy plays a pivotal role in the regeneration of damaged endometrium. Previous studies have demonstrated the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs) through diverse administration ways. However, the homing, survival and differentiation potential of these differently administered BMSCs are poorly defined and the best route of administration is not well defined. Herein, we aim to compare the engraftment, retaining time and therapeutic efficiency of differently administered BMSCs. To achieve this, GFP/Luc-labeled BMSCs administered in two modes were assessed in a rat thin endometrium model: either into the damaged horns directly or through the ipsilateral iliac artery. The retaining time and hemi-quantitative distribution were evaluated by in vivo bioluminescence imaging and immune-histological analysis. Locally administered BMSCs were strongly detected in the abdomen at the first 4 days post-treatment, but underwent a rapid decrease in luminescent signal afterward and were rarely found 28 days after treatment. In contrast, the remaining time of BMSCs injected through the iliac artery was longer, reflected by more GFP-positive cells detected in the uterine section 28 days post-treatment. Differentiation towards endometrial stromal cells was observed. Both routes of administration contributed to the restoration of damaged endometrium, showing a comparable increase in the endometrial thickness and a decrease in fibrosis. However, more importantly, higher expression of LIF and VEGF, better recruitment and longer retainment were found in the intra-arterial administration, contributing to the establishment of optimal administration mode in the clinical practice.