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2 型糖尿病大鼠脂肪源干细胞在勃起功能障碍大鼠模型中保留积极作用。

Adipose-Derived Stem Cells from Type 2 Diabetic Rats Retain Positive Effects in a Rat Model of Erectile Dysfunction.

机构信息

Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense, Denmark.

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark.

出版信息

Int J Mol Sci. 2022 Feb 1;23(3):1692. doi: 10.3390/ijms23031692.

Abstract

Erectile dysfunction is a common complication associated with type 2 diabetes mellitus (T2DM) and after prostatectomy in relation to cancer. The regenerative effect of cultured adipose-derived stem cells (ASCs) for ED therapy has been documented in multiple preclinical trials as well as in recent Pase 1 trials in humans. However, some studies indicate that diabetes negatively affects the mesenchymal stem cell pool, implying that ASCs from T2DM patients could have impaired regenerative capacity. Here, we directly compared ASCs from age-matched diabetic Goto-Kakizaki (ASC) and non-diabetic wild type rats (ASC) with regard to their phenotypes, proteomes and ability to rescue ED in normal rats. Despite ASC exhibiting a slightly lower proliferation rate, ASC and ASC proteomes were more or less identical, and after injections to corpus cavernosum they were equally efficient in restoring erectile function in a rat ED model entailing bilateral nerve crush injury. Moreover, molecular analysis of the corpus cavernosum tissue revealed that both ASC and ASC treated rats had increased induction of genes involved in recovering endothelial function. Thus, our finding argues that T2DM does not appear to be a limiting factor for autologous adipose stem cell therapy when correcting for ED.

摘要

勃起功能障碍是 2 型糖尿病(T2DM)和前列腺癌根治术后常见的并发症。在多个临床前试验以及最近的 1 期人体试验中,培养的脂肪源性干细胞(ASCs)在 ED 治疗中的再生作用得到了证实。然而,一些研究表明,糖尿病会对间充质干细胞池产生负面影响,这意味着来自 T2DM 患者的 ASC 可能具有受损的再生能力。在这里,我们直接比较了年龄匹配的糖尿病 Goto-Kakizaki(ASC)和非糖尿病野生型大鼠(ASC)的 ASC,观察它们的表型、蛋白质组学以及在正常大鼠中恢复 ED 的能力。尽管 ASC 表现出稍低的增殖率,但 ASC 和 ASC 的蛋白质组学几乎相同,并且在注射到海绵体后,它们在涉及双侧神经挤压损伤的大鼠 ED 模型中恢复勃起功能的效率相同。此外,对海绵体组织的分子分析表明,接受 ASC 和 ASC 治疗的大鼠均增加了参与恢复内皮功能的基因的诱导。因此,我们的发现表明,在纠正 ED 时,T2DM 似乎不是自体脂肪干细胞治疗的限制因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f76/8836282/d06f43826f74/ijms-23-01692-g001.jpg

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