Cell-free therapy with the secretome of adipose tissue-derived stem cells in rats’ frozen-thawed ovarian grafts

Abstract

The use of secretome may be a new strand of cell therapy, which is equal to or even superior to the injection of live cells, called cell-free therapy. In ovarian transplantation, this approach may be a therapeutic possibility for the ovarian graft in hypoxia. We designed the present study to evaluate whether the cell-free therapy with the secretome of adipose tissue-derived stem cells (ASCs) in rat frozen-thawed ovarian grafts could protect a graft against ischemic injury. A single dose of rat ASCs secretome or vehicle was injected into the bilateral frozen-thawed ovaries of 18 adult female rats immediately after an autologous transplant. Nine animals were used to control the cryopreservation protocol and were evaluated before and after the cryopreservation process. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability by trypan blue, graft morphology by HE, and apoptosis by TUNEL and cleaved-caspase-3 were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (p > 0.05). However, compared with the vehicle-treated grafts, the morphology of the secretome-treated grafts was impaired, showing reduced follicular population and increased apoptosis (p < 0.05). ASC secretome impaired the rat frozen-thawed ovarian graft from ischemic injury. However, more studies are needed to evaluate the factors involved and the possibility of applying the secretome in scaffolds to optimize its use.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1054-3) contains supplementary material, which is available to authorized users.

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

“…When culturing SVF in a defined media it forms a homogenous population of mesenchymal stem cells dubbed adipose stem cells (ASCs). ASCs are multipotent progenitor cells that can selfrenew, differentiate into other cell types [13,14], and secrete multiple growth factors and cytokines resulting in regenerative effects in various diseases including ED [15][16][17][18]. We have previously demonstrated safety and potential therapeutic efficacy of freshly isolated SVF in a Phase I clinical trial treating ED patients following radical prostatectomy [19].…”

High-Efficient Production of Adipose-Derived Stem Cell (ADSC) Secretome Through Maturation Process and Its Non-scarring Wound Healing Applications

“…Among the several sources of stem cells, enormous attention has been focusing on the adipose tissue-derived stem cells (ADSCs) due to the easy isolating procedure, liposuction, with a higher harvest rate than bone marrow ( Hodgkinson et al, 2020 ). The ADSC-secretome has been proven to be useful not only for regenerating non-healing cutaneous and corneal wounds, cardiovascular disease, etc., but also to be utilized in a cosmeceutical application ( Damous et al, 2018 ; Lombardi et al, 2019 ).…”

Decreased ovarian reserve and ovarian morphological alterations in female rat offspring exposed to a ketogenic maternal diet

“…The morphological characteristics of follicles were determined according to the previous report as follows 10,11 :…”

“…• Primordial follicle, a single oocyte surrounded by a monolayer of squamous cells; • Primary follicle, an oocyte without antrum surrounded by a monolayer or more than one cuboid or prismatic cell; • Secondary follicle, consisting of a single oocyte and a single antrum; • Antral follicle, consisting of a single oocyte and enlarged antrum; • Corpus luteum, consisting of large volumes of luteal cells surrounded by capillary blood vessels 10,11 .…”