Research Article: Systemically transplanted mesenchymal stem cells induce vascular-like structure formation in a rat model of vaginal injury

Date Published: June 13, 2019

Publisher: Public Library of Science

Author(s): Ofra Ben Menachem- Zidon, Michal Gropp, Etti Ben Shushan, Benjamin Reubinoff, David Shveiky, Gianpaolo Papaccio.


The beneficial effect of mesenchymal stem cells (MSCs) on wound healing is mostly attributed to a trophic effect that promotes angiogenesis. Whether MSCs can contribute to the formation of new blood vessels by direct differentiation is still controversial. Pelvic floor dysfunction (PFD) is a group of disorders that negatively affect the quality of women’s lives. Traditional vaginal surgical repair provides disappointing anatomical outcome. Stem cell transplantation may be used to supplement surgery and improve its outcome. Here we aimed to examine the engraftment, survival, differentiation and angiogenic effect of transplanted MSCs in a vaginal injury rat model. MSCs were obtained from the bone marrow of Sprague Drawley (SD) rats, expanded and characterized in vitro. The MSCs expressed CD90 and CD29, did not express CD45, CD34, CD11b and CD31 and could differentiate into osteogenic, chondrogenic and adipogenic lineages. Cells were labeled with either PKH-26 or GFP and transplanted systemically or locally to female SD rats, just after a standardized vaginal incision was made. Engraftment after local transplantation was less efficient at all-time points compared to systemic administration. In the systemically transplanted animal group, MSCs migrated to the injury site and were present in the healed vagina for at least 30 days. Both systemic and local MSCs transplantation promoted host angiogenesis. Systemically transplanted MSCs created new vascular-like structures by direct differentiation into endothelium. These findings pave the way to further studies of the potential role of MSCs transplantation in improving surgical outcome in women with PFD.

Partial Text

Mesenchymal stem cells (MSCs) have been reported to possess a potential therapeutic effect in various human pathological conditions [1–3]. They can be isolated from several sources, including bone marrow [4], adipose tissue [5], muscles [6], dental pulp [7,8], endometrium [9] and umbilical cord [10,11].

This study was approved by the Hebrew University Animal Care and Use Committee. Sprague Dawley (SD) female rats were held at the SPF unit in Hadassah medical school with food and water ad libitum. All rats were 10 weeks old, with an average weight of 200gr, when operated.

In this study, we have shown that systemic transplantation of bone-marrow derived MSCs after vaginal incision was associated with homing of the transplanted cells to the injury site and their survival for at least 30 days. MSCs transplantation induced the formation of new blood vessels by angiogenesis. In addition, the transplanted cells differentiated in vivo into endothelial cells within capillary-like structures.




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