Harnessing the therapeutic potential of bone marrow-derived stem cells for sciatic nerve regeneration in diabetic neuropathy.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes that affects the angiogenesis and myelination of peripheral nerves. In this study, we investigated the potential of mesenchymal stem cells (MSCs) transplantation to improve DPN by enhancing angiogenesis and remyelination in the sciatic nerve of streptozotocin (STZ)-induced diabetic female rats. The purpose of this study was to evaluate the therapeutic potential of mesenchymal stem cells as a possiblity for clinical intervention to alleviate the symptoms of diabetic peripheral neuropathy. We examined whether transplanted mesenchymal stem cells can produce new and restored angiogenesis, as well as promoting myelination. Overall, our findings suggest that MSCs transplantation has neuroprotective effects. This is particularly the case for Schwann cells. Transplantation may stimulate angiogenesis as well as remyelination of the sciatic nerve in experimentally-induced diabetic peripheral neuropathy. Behavioral assays, histological analysis, and molecular techniques were used to assess the effects of MSCs transplantation. Our results demonstrate that in diabetic rats signs of neuropathy were reversed following a single administration of bone marrow-derived MSCs. Morphological and morphometric analysis of the sciatic nerve revealed that diabetic rats displayed structural alterations that were attenuated with MSCs transplantation.Immunostaining analysis showed increased expression of S100 and VEGF in the sciatic nerve following MSCs transplantation. Western blotting analysis also revealed elevated levels of VEGF and CD31 in rats treated with MSCs compared to diabetic rats.

Assessment of therapeutic efficacy of adipose tissue-derived mesenchymal stem cells administration in hyperlipidemia-induced aortic atherosclerosis in adult male albino rats.

Atherosclerosis (AS) is a common disease seriously detrimental to human health. AS is a chronic progressive disease related to inflammatory reactions. The present study aimed to characterize and evaluate the effects of adipose tissue stem cells (ADSCs) in high-fat diet-induced atherosclerosis in a rat model. The present study comprises thirty-six rats and they were divided into three groups: the control group, the high-fat diet (HFD) group; which received a high-fat diet, and the high-fat diet + stem cells (HFD+SC) group; which was fed with a high-fat diet along with the administration of intravenous ADSCs. Food was given to the animals for 20 weeks to establish dyslipidemia models. After 20 weeks, animals were sacrificed by cervical dislocation; blood was collected to measure total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL); aortae were collected to detect morphologic changes. Rats of the HFD group showed a significant increase in body weight (B.Wt), altered lipid profile increased expression of inducible nitric oxide synthase (iNOS), and decreased expression of endothelial nitric oxide synthase (eNOS). However, in HFD+SC there was a significant decrease in body weight gain and an improvement in lipid profile. Histopathological and ultrastructural variations observed in the aorta of the HFD group when treated with ADSCs showed preserved normal histological architecture and reduced atherosclerosis compared with the HFD group. This was evidenced by laboratory, histological, immunohistochemical, and morphometric studies. Thus, ADSCs reduced TC, TG, and LDL, reduced the expression of iNOS, and increased the expression of eNOS. The high-fat diet was likely to cause damage to the wall of blood vessels. Systemically transplanted ADSCs could home to the aorta, and further protect the aorta from HFD-induced damage.

Circumferential Esophageal Reconstruction Using a Tissue-engineered Decellularized Tunica Vaginalis Graft in a Rabbit Model.

BACKGROUND: Pediatric surgeons have faced esophageal reconstruction challenges for decades owing to a variety of congenital and acquired conditions. This work aimed to introduce a reproducible and efficient approach for creating tissue-engineered esophageal tissue using bone marrow mesenchymal stem cells (BMSCs) cultured in preconditioned mediums seeded on a sheep decellularized tunica vaginalis (DTV) scaffold for partial reconstruction of a rabbit's esophagus. METHODS: DTV was performed using SDS and Triton X-100 solutions. The decellularized grafts were employed alone (DTV group) or after recellularization with BMSCs cultured for 10 days in preconditioned mediums (RTV group) for reconstructing a 3 cm segmental defect in the cervical esophagus of rabbits (n = 20) after the decellularization process was confirmed. Rabbits were observed for one month, after which they were euthanized, and the reconstructed esophagi were harvested for histological analysis. RESULTS: Six rabbits in the DTV group and eight rabbits in the RTV group survived until the end of the one-month study period. Despite histological examination demonstrating that both grafts completely repaired the esophageal defect, the RTV graft demonstrated a histological structure similar to that of the normal esophagus. The reconstructed esophagi in the RTV group revealed the arrangement of the different layers of the esophageal wall with the formation of newly formed blood vessels and Schwann-like cells. CONCLUSION: DTV xenograft is a novel scaffold that promotes cell adhesion and differentiation and might be effectively utilized for regenerating esophageal tissue, paving the way for future clinical trials in pediatric patients.

Alleviation of doxorubicin-induced cardiotoxicity in rat by mesenchymal stem cells and olive leaf extract via MAPK/ TNF-α pathway: Preclinical, experimental and bioinformatics enrichment study.

BACKGROUND: Toxic cardiomyopathies were a potentially fatal adverse effect of anthracycline therapy. AIM: This study was conducted to demonstrate the pathogenetic, morphologic, and toxicologic effects of doxorubicin on the heart and to investigate how the MAPK /TNF-α pathway can be modulated to improve doxorubicin-Induced cardiac lesions using bone marrow-derived mesenchymal stem cells (BM-MSCs) and olive leaf extract (OLE). METHODS: During the study, 40 adult male rats were used. Ten were used to donate MSCs, and the other 30 were split into 5 equal groups: Group I was the negative control, Group II obtained oral OLE, Group III obtained an intraperitoneal cumulative dose of DOX (12 mg/kg) in 6 equal doses of 2 mg/kg every 48 h for 12 days, Group IV obtained intraperitoneal DOX and oral OLE at the same time, and Group V obtained intraperitoneal DOX and BM-MSCs through the tail vein at the same time for 12 days. Four weeks after their last dose of DOX, the rats were euthanized. By checking the bioinformatic databases, a molecularly targeted path was selected. Then the histological, immunohistochemistry, and gene expression of ERK, JNK, NF-κB, IL-6, and TNF-α were done. RESULTS: Myocardial immunohistochemistry revealed severe fibrosis, cell degeneration, increased vimentin, and decreased CD-31 expression in the DOX-treated group, along with a marked shift in morphometric measurements, a disordered ultrastructure, and overexpression of inflammatory genes (ERK, NF-κB, IL-6, and TNF-α), oxidative stress markers, and cardiac biomarkers. Both groups IV and V displayed reduced cardiac fibrosis or inflammation, restoration of the microstructure and ultrastructure of the myocardium, downregulation of inflammatory genes, markers of oxidative stress, and cardiac biomarkers, a notable decline in vimentin, and an uptick in CD-31 expression. In contrast to group IV, group V showed a considerable beneficial effect. CONCLUSION: Both OLE and BM-MSCs showed an ameliorating effect in rat models of DOX-induced cardiotoxicity, with BM-MSCs showing a greater influence than OLE.

Bone-Marrow-Derived Mesenchymal Stem Cells, Their Conditioned Media, and Olive Leaf Extract Protect against Cisplatin-Induced Toxicity by Alleviating Oxidative Stress, Inflammation, and Apoptosis in Rats.

BACKGROUND: Hepatic and renal damage is a cisplatin (Cis)-induced deleterious effect that is a major limiting factor in clinical chemotherapy. OBJECTIVES: The current study was designed to investigate the influence of pretreatment with olive leaf extract (OLE), bone-marrow-derived mesenchymal stem cells (BM-MSC), and their conditioned media (CM-MSC) against genotoxicity, nephrotoxicity, hepatotoxicity, and immunotoxicity induced by cisplatin in rats. METHODS: The rats were randomly divided into six groups (six rats each) as follows: Control; OLE group, treated with OLE; Cis group, treated with a single intraperitoneal dose of Cis (7 mg/kg bw); Cis + OLE group, treated with OLE and cisplatin; Cis + CM-MSC group, treated with BM-MSC conditioned media and Cis; and Cis + MSC group, treated with BM-MSC in addition to Cis. RESULTS: Cis resulted in a significant deterioration in hepatic and renal functions and histological structures. Furthermore, it increased inflammatory markers (TNF-α, IL-6, and IL-1ß) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content, total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activity in hepatic and renal tissues. Furthermore, apoptosis was evident in rat tissues. A significant increase in serum 8-hydroxy-2-deoxyguanosine (8-OH-dG), nitric oxide (NO) and lactate dehydrogenase (LDH), and a decrease in lysozyme activity were detected in Cis-treated rats. OLE, CM-MSC, and BM-MSC have significantly ameliorated Cis-induced deterioration in hepatic and renal structure and function and improved oxidative stress and inflammatory markers, with preference to BM-MSC. Moreover, apoptosis was significantly inhibited, evident from the decreased expression of Bax and caspase-3 genes and upregulation of Bcl-2 proteins in protective groups as compared to Cis group. CONCLUSIONS: These findings indicate that BM-MSC, CM-MSC, and OLE have beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the hepatotoxicity, nephrotoxicity, immunotoxicity, and genotoxicity in a rat model.

Urine-Derived Stem Cells Versus Their Lysate in Ameliorating Erectile Dysfunction in a Rat Model of Type 2 Diabetes.

Background: Diabetic erectile dysfunction (DED) is a significant consequence of diabetes mellitus, and it is a multifactorial phenomenon that has no definitive treatment until now. Many therapeutic options provide symptomatic improvement rather than addressing the underlying etiology or restoring normal function. Stem cell (SC) therapy represents a potential hope in DED management. It is well established that the regenerative effect of stem cells can be attained by their paracrine action and their ability to differentiate into many cell lineages, including endothelial and smooth muscle cells. Hence, we tried to compare the effects of transplantation of urine-derived stem cells (USCs) or their lysate (USC-L) into the corpora cavernosa (CCs) of rats with DED. Materials and Methods: A total of 55 adult male Wistar rats were included in this study. USCs were obtained from ten healthy rats. Another ten rats did not subject to any intervention and served as a control (group I). Type 2 DM and DED were induced in the remaining 35 rats, but DED was tested and proved in only 24 rats, which were randomly divided into three groups (n = 8 in each). The DED group (group II) and either USCs (2 × 106 cells) or their lysate (200 µl) were transplanted into the CCs of each rat in the other two groups (groups III and IV), respectively. Results: Although the DED rats exhibited deterioration in all copulatory functions as compared to the control group, our histopathological, immunohistochemical, and morphometric results revealed that both USCs and USC-L have significantly restored the cavernous spaces, the ultrastructures of the endothelium that line the cavernous spaces, collagen/smooth muscle ratio, and the mean area percentage of α-SMA in the CCs as compared to DED rats. A respectable number of USCs was detected in the CCs of group III at the 4th week after transplantation, but this number significantly declined by the 8th week. Conclusion: Both USCs and USC-L can repair the structure and ultrastructure of CCs and improve the copulatory functions in the DED rat model. However, USC-L could be better used in DED to guard against the strange behavior of USCs after transplantation and their decreased survivability with time.

Harderian gland-derived stem cells as a cytotherapy in a guinea pig model of carboplatin-induced hearing loss.

BACKGROUND: Stem cells therapy of hearing loss is a challenging field due to lacking self-regenerative capacity of cochlea. Harderian gland of guinea pigs was thought to harbour a unique type of progenitors which could restore the damaged cochlear tissues. THE AIM: of this study was to isolate Harderian gland derived stem cells (HG-SCs) and investigate their efficacy in restoring the damaged cochlear tissue in carboplatin-induced hearing loss. METHODOLOGY: Sixty female and 10 male pigmented guinea pigs were used; the male animals were HG-SCs donors, while the females were assigned into 3 groups; control, hearing loss (HL) and HG-SC-treated groups. Auditory reflexes were assessed throughout the study. The animals were euthanized 35 days after HG-SCs transplantation, the cochleae were extracted and processed for assessment by light microscope and scanning electron microscope. Morphometric assessment of stria vascularis thickness, hair cells and spiral ganglia neuronal number and optical density of TLR4 expression were done. RESULTS: The isolated HG-SCs had the same morphological and phenotypical character as mesenchymal stem cells. HL group revealed destruction of organ of Corti, stria vascularis and spiral ganglion with decreased morphometric parameters. Restoration of both cochlear structure and function was observed in HG-SC-treated group along with a significant increase in IHCs, OHCs numbers, stria vascularis thickness and spiral ganglionic cell count to be close to the values of control group. CONCLUSION: The isolated HG-SCs were proved to restore structure and function of cochlea in guinea pig model of hearing loss.

Role of bone marrow derived mesenchymal stromal cells and Schwann-like cells transplantation on spinal cord injury in adult male albino rats.

BACKGROUND: Spinal cord injury is a considerable health impact accompanied with physical, psychological and economic burden. Bone marrow derived mesenchymal stromal cells (BM-MSCs) transplantation was found to produce neuronal regenerative effects. Schwann-like cells differentiated from BM-MSCs have myelin-forming ability. AIM OF THE WORK: To compare the ability of BM-MSCs versus Schwann like cells to promote recovery of spinal cord injury. MATERIAL AND METHODS: Adult male albino rats were used throughout the study. BM-MSCs were harvested from femora of rats. Sciatic nerves were extracted and used in the preparation of the induction culture medium for differentiation of BM-MSCs into Schwann-like cells. Rats were divided into control, spinal cord injured (SCI), spinal cord injured plus BM-MSCs transplantation (BM-MSC) and spinal cord injured plus Schwann-like cells transplantation (Sn) groups. BBB scale assessment was performed before and after SCI in all rats. Rats were euthanized at the end of the 7th week and spinal cords were dissected and processed for light and transmission electron microscopic examinations. RESULTS: Spinal cord sections of SCI group revealed cavitation, necrosis and demyelination. BM-MSC and Sn groups showed both functional and structural improvement compared to SCI group with better BBB score and histopathological features in the BM-MSC group and more expression of S100 in the Sn group. CONCLUSION: Transplantation of BM-MSCs and Schwann-like cells improved the structural and functional alterations of spinal cord injury with better improvement in BM-MSC group.

Therapeutic efficacy of olfactory stem cells in rotenone induced Parkinsonism in adult male albino rats.

BACKGROUND: Olfactory stem cells (OSCs) are found in the olfactory mucosa and olfactory bulb and have the capacity to proliferate and differentiate along multiple tissue lineages. Rotenone; widely used insecticide has a neurodegenerative effect on the dopaminergic cells of substantia nigra (SN) of midbrain producing Parkinsonism. The aim of this study is to isolate rat OSCs from olfactory mucosa and olfactory bulb, culture these OSCs in suitable medium to allow for their proliferation to be used in the treatment of Parkinsonism induced by rotenone. METHODS: The characteristics of OSCs, the effects of rotenone on the SN of midbrain and the curative effect of OSCs on the substantia nigra were determined morphologically, immunohistochemically, and by transmission electron microscopy. PKH 26; immunofluorescent dye was used as a cell tracer to locate the transplanted cells in host midbrain. RESULTS: OSCs were spindle shaped with irregular processes, and were positive for CD44 and Nestin and negative for CD34. Subcutaneous rotenone produced Parkinsonism through producing degeneration of the dopaminergic cells of SN of the midbrain. Transplantation of OSCs produced restoration of the normal structure of SN and dopaminergic cells and improves the clinical manifestations of Parkinsonism. CONCLUSION: These results indicate that, the isolated rat OSCs can proliferate and expand in vitro when culture in suitable medium and these cells can exert therapeutic effects in Parkinsonism by recruitment in SN and restoration of the structure and function of dopaminergic cells.