Bone marrow-derived mesenchymal stem cells combined with gonadotropin therapy restore postnatal oogenesis of chemo-ablated ovaries in rats via enhancing very small embryonic-like stem cells.

BACKGROUND: Very small embryonic-like stem cells (VSELs) are a rare population within the ovarian epithelial surface. They contribute to postnatal oogenesis as they have the ability to generate immature oocytes and resist the chemotherapy. These cells express markers of pluripotent embryonic and primordial germ cells. OBJECTIVE: We aimed to explore the capability of VSELs in restoring the postnatal oogenesis of chemo-ablated rat ovaries treated with bone marrow-derived mesenchymal stem cells (BM-MSCs) combined with pregnant mare serum gonadotropin (PMSG). METHODS: Female albino rats were randomly assigned across five groups: I (control), II (chemo-ablation), III (chemo-ablation + PMSG), IV (chemo-ablation + MSCs), and V (chemo-ablation + PMSG + MSCs). Postnatal oogenesis was assessed through measurement of OCT4, OCT4A, Scp3, Mvh, Nobox, Dazl4, Nanog, Sca-1, FSHr, STRA8, Bax, miR143, and miR376a transcript levels using qRT-PCR. Expression of selected key proteins were established as further confirmation of transcript expression changes. Histopathological examination and ovarian hormonal assessment were determined. RESULTS: Group V displayed significant upregulation of all measured genes when compared with group II, III or IV. Protein expression confirmed the changes in transcript levels as group V displayed the highest average density in all targeted proteins. These results were confirmed histologically by the presence of cuboidal germinal epithelium, numerous primordial, unilaminar, and mature Graafian follicles in group V. CONCLUSION: VSELs can restore the postnatal oogenesis in chemo-ablated ovaries treated by BM-MSCs combined with PMSG.

Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway.

BACKGROUND: Diabetic foot ulceration is a serious chronic complication of diabetes mellitus characterized by high disability, mortality, and morbidity. Platelet-rich plasma (PRP) has been widely used for diabetic wound healing due to its high content of growth factors. However, its application is limited due to the rapid degradation of growth factors. The present study aimed to evaluate the efficacy of combined adipose-derived mesenchymal stem cells (ADSCs) and PRP therapy in promoting diabetic wound healing in relation to the Notch signaling pathway. METHODS: Albino rats were allocated into 6 groups [control (unwounded), sham (wounded but non-diabetic), diabetic, PRP-treated, ADSC-treated, and PRP+ADSCs-treated groups]. The effect of individual and combined therapy was evaluated by assessing wound closure rate, epidermal thickness, dermal collagen, and angiogenesis. Moreover, gene and protein expression of key elements of the Notch signaling pathway (Notch1, Delta-like canonical Notch ligand 4 (DLL4), Hairy Enhancer of Split-1 (Hes1), Hey1, Jagged-1), gene expression of angiogenic marker (vascular endothelial growth factor and stromal cell-derived factor 1) and epidermal stem cells (EPSCs) related gene (ß1 Integrin) were assessed. RESULTS: Our data showed better wound healing of PRP+ADSCs compared to their individual use after 7 and 14 days as the combined therapy caused reepithelialization and granulation tissue formation with a marked increase in area percentage of collagen, epidermal thickness, and angiogenesis. Moreover, Notch signaling was significantly downregulated, and EPSC proliferation and recruitment were enhanced compared to other treated groups and diabetic groups. CONCLUSIONS: These data demonstrated that PRP and ADSCs combined therapy significantly accelerated healing of diabetic wounds induced experimentally in rats via modulating the Notch pathway, promoting angiogenesis and EPSC proliferation.

Protective Effect of Curcumin against Sodium Salicylate-Induced Oxidative Kidney Damage, Nuclear Factor-Kappa Dysregulation, and Apoptotic Consequences in Rats.

This study examined the effect of sodium salicylates (SS), alone and in combination with curcumin (CUR), on kidney function and architecture in rats. Five rat groups were given 1 mL physiological saline/rat orally, 1 mL olive oil/rat orally, 50 mg CUR/kg bwt orally, 300 mg SS/kg bwt intraperitoneally, or CUR+SS for 15 days. The hematological indices, serum protein profile, serum electrolytes balance, oxidative stress, and lipid peroxidation of kidney tissues were assessed. The histopathological examination and immune expression of Caspase-3 and nuclear factor kappa (NF-κB) were conducted. The findings showed that SS injection induced nephrotoxic activity, including increased serum urea, creatinine, and uric acid levels. It also caused apparent pathological alterations with increased Caspase-3 and NF-κB immuno-expression. In addition, thrombocytopenia, leukocytosis, neutrophilia, hyponatremia, hypochloremia, hypocalcemia, and hypomagnesemia but not hyperkalemia and hyperphosphatemia were evident in SS-injected rats. Moreover, SS exposure increased serum α1 globulin, renal tissue malondialdehyde, and Caspase-3 levels but superoxide dismutase, glutathione peroxidase, and Bcl-2 levels declined. Meanwhile, CUR significantly counteracted the SS harmful impacts on kidneys but SS+CUR co-administration induced an anemic condition. Overall, CUR has an evident protective role against SS-induced renal damage, but the disturbed hematological alterations should be carefully taken into consideration in their combined use.