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系统移植间充质干细胞在大鼠阴道损伤模型中诱导血管样结构形成。

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

机构信息

The Hadassah Human Embryonic Stem Cell Research Center, Goldyne Savad Institute of Gene Therapy, Hadassah - Hebrew University Hospital, Jerusalem, Israel.

Department of Obstetrics and Gynecology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

出版信息

PLoS One. 2019 Jun 13;14(6):e0218081. doi: 10.1371/journal.pone.0218081. eCollection 2019.

Abstract

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.

摘要

间充质干细胞(MSCs)对伤口愈合的有益作用主要归因于促进血管生成的营养作用。MSCs 是否可以通过直接分化为新血管形成做出贡献仍存在争议。盆底功能障碍(PFD)是一组对女性生活质量产生负面影响的疾病。传统的阴道手术修复提供的解剖学结果令人失望。干细胞移植可用于补充手术并改善其结果。在这里,我们旨在检查移植的 MSCs 在阴道损伤大鼠模型中的植入、存活、分化和血管生成作用。MSCs 从 Sprague Drawley(SD)大鼠的骨髓中获得,在体外进行扩增和鉴定。MSCs 表达 CD90 和 CD29,不表达 CD45、CD34、CD11b 和 CD31,并且可以分化为成骨、软骨和成脂谱系。细胞用 PKH-26 或 GFP 标记,然后全身或局部移植到雌性 SD 大鼠中,就在标准化阴道切开后进行。与全身给药相比,局部移植后的植入在所有时间点都效率较低。在全身移植动物组中,MSCs 迁移到损伤部位,并在愈合的阴道中存在至少 30 天。全身和局部 MSCs 移植均促进了宿主血管生成。全身移植的 MSCs 通过直接分化为内皮细胞形成新的血管样结构。这些发现为进一步研究 MSCs 移植在改善 PFD 女性手术结果中的潜在作用铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c457/6563972/1b0cf909c2ab/pone.0218081.g001.jpg

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