Simultaneous treatment with cells and rosemary extract ameliorates 6-OHDA-induced toxicity in the hippocampus of mice.

In this study, we delved into the hippocampal region to understand the effects of adipose stem cells (ADSCs) and rosemary extract (RE). Our main objective was to explore how these substances influence spatial memory, neurotrophins, and changes in antioxidant enzymes. Moreover, we meticulously investigated the impact of dopamine deficiency, a notable characteristic linked with Parkinson's disease (PD), on memory impairment. This study comprised five groups of Wistar rats - all male, all selected randomly. We labeled two of these gatherings "lesion" (L) and "sham" (SH). Each got injections in the bilateral form with 6 µg - one group getting saline, while another got 6-OHDA. From couple weeks before the neurotoxin injection to 8 weeks later on, our lesion cohort was treated with rosemary at a dosage rate of 50 mg/kg body weight - let's call it RE for simplicity sake. Moreover, there is also this other lot, designated as cell-transplanted lesion group or catchy exercise (CE) as we prefer to interpret them; they had cell transplants conducted exactly 7 days after receiving their respective injections. Bringing up the rear, we got a group treated with both cell transplant and rosemary (CE+R). We performed spatial memory tests at 4 weeks, then again at 8. At the end of eighth week, the brains were extracted for q-PCR, enzymatic and immunohistochemical studies. Turning our gaze toward a comparison between the CE+R and CE groups versus the L group, we spot an intriguing drop in escape latency time. There is also more time spent in quadrants. Digging deeper into this matter, the CE+R bunch unveiled a clear surge when it comes to the expression of four genes, namely NGF, BDNF, NT3, and NT4! This was notable especially while comparing with both R and even other fellows from its very own broader group - CE. In a bit complex bit related to enzyme activity now, there is some good news as well for those in favor of potent antioxidants such as GPx or SOD. CE + R group, showed a significant increase of GPX and SOD enzymes, compared to the SH and L groups, and a significant decrease of MDA activity as compared to other treated groups. A significant decrease of escape latency and increase of time in quadrant were observed in the CE+R and CE groups compared to L group. What's more, the levels of MDA in the CE+R group plummeted significantly when set up against the SH group. Wrapping things up, a definite downscale was observed in the density of GFAP-positive cells throughout different regions located within the hippocampus; this decline presented itself not solely in treatment groups but gripped onto those falling under SH as well, especially when compared to its comrade - the L group. Using ADSCs and taking RE orally have shown promising results in improving memory issues linked with PD.

Innovative services in home health nursing: a scoping review protocol.

INTRODUCTION: Advances in the use of technology in home health nursing (HHN) not only can facilitate the delivery of home care but can also influence the entire healthcare system. Additionally, it can contribute to the individual autonomy in the area of health. The aim of this scoping review protocol is to identify, describe and map the types of innovative services and their delivery approaches in the HHN structure worldwide. METHODS AND ANALYSIS: The main question of the research is as follows: what are different types of innovative services and their delivery approaches in the HHN structure around the world? The Joanna Briggs Institute (JBI) method for scoping reviews will guide the conducting this scoping review, and the participants, concept and context framework will be used as eligibility criteria. MEDLINE databases via PubMed, Embase, Cochrane Library, Scopus, Web of Science, Science Direct, Persian scientific databases and grey literature will be searched prior to May 2024 to include eligible studies, without any language restrictions. To be included, studies will be reviewed by two independent reviewers. A data extraction form developed for the study purpose will be used to extract the data relevant to the review questions. Data analysis will be performed based on each innovative service and answering the subquestions about it. According to the concepts of interest, the results will be analysed and presented using tables, figures, images and a narrative summary. ETHICS AND DISSEMINATION: This study will not involve human or animal participants. Data will be sourced from the published literature. To be published, the results of the study will be submitted to an international peer-reviewed, open-access journal as well as scientific meetings on HHN and innovative services research.

Effect of in ovo feeding of folic acid on Disabled-1 and gga-miR-182-5p expression in the cerebral cortex of chick embryo.

Folate (vitamin B9) has been shown to reduce the prevalence of neural tube defects (NTDs). Many genes comprising Disabled-1 (DAB1) and miRNAs have been shown to play important role in normal brain development. Reelin-signalling has been shown to play key role in regulating of neuronal migration during brain development. The aim of this study was to evaluate the effects of in ovo administration of folic acid (FA) on DAB1 and gga-miR-182-5p expression in the cerebral cortex of chick embryo. A total number of 30 hatching eggs were used in this study. The number of 10 eggs were injected into the yolk sac with FA (150 µg/egg), 10 eggs by normal saline (sham group) on embryonic day 11 and 10 eggs were left without injection as control. Then the cerebral cortices were collected on E19 and the expression of DAB1 and gga-miR-182-5p was studied by Real-Time PCR. The results showed that DAB1 expression in the cerebral cortex of FA-treated, sham and control were 2.51 ± 0.13, 1.01 ± 0.04 and 1.03 ± 0.04 fold changes, respectively, and this amount for gga-miR-182-5p were 0.54 ± 0.03, 1.09 ± 0.07 and 1.00 ± 0.06-fold change respectively. Statistical analysis showed that there is a significant increase in DAB1 and a decrease in gga-miR-182-5p expression in FA injected cerebral cortex as compared either with either SHAM or control (p < 0.0001). But, no significant change in DAB1 and gga-miR-182-5p expression was observed between sham and the control group (p = 0.99 and p = 0.57 respectively). It is concluded that in ovo feeding of FA increases DAB1 and decreases gga-miR-182-5p expression in the developing chick cerebral cortex.

The relationship between moral courage and providing safe care in nurses: A cross-sectional study.

BACKGROUND: Moral courage is one of the moral virtues, which can have a great impact on the provision of safe care for patients. Providing safe care is one of the most significant and fundamental principles of healthcare. This study aimed to determine the relationship between moral courage and safe care among nurses and explain the factors predicting safe care. MATERIALS AND METHODS: This is a cross-sectional study conducted on 172 nurses who worked in selected hospitals affiliated with the Iran University of Medical Sciences in 2019. For this purpose, self-report questionnaires on moral courage and safe nursing care were used. The collected data were analyzed in the Statistical Package for Social Sciences (SPSS) version 23.0 using descriptive (mean, standard deviation, percentage, and frequency) and inferential (Pearson's correlation coefficient and multiple linear regression) statistics. P values less than 0.05 were considered statistically significant. RESULTS: Mean scores of nurses' moral courage and safe care were desirable (407.57 ± 53.97) and satisfactory (311.31 ± 39.48), respectively. There was a significant correlation between the scores of nursing safe care and moral courage (r = 0.69, P < 0.001). Moral courage, gender, and work experience explained 54% of the variance of nursing safe care. CONCLUSION: The results showed that there is a positive and significant relationship between safety care and moral courage. It seems that increasing nurses' awareness of ethical principles leads to their courageous ethical behaviors, and safety and high-quality care should be one of the goals of all healthcare professionals. Also, the results of this study support the need to improve the knowledge and awareness of nurses and nurse managers regarding the importance of moral courage in providing safe nursing care and improving patient safety.

Effects of pulsed electromagnetic fields and N-acetylcysteine on transplantation of vitrified mouse ovarian tissue.

In this experimental study, adult female NMRI mice were randomly assigned to five groups: control ;(fresh ovarian transplantation, OT); sham ;(vitrified OT); NAC ;(vitrified OT treated with N-acetyl cysteine, NAC); EMF ;(vitrified OT treated with pulsed electromagnetic fields, PEMF); and NAC+EMF ;(vitrified OT combined with NAC and PEMF). We conducted histological assessments to evaluate follicle reservation and vascularization. Furthermore, we examined the relative expression of Fgf-2, Vegf, Tnf-α, Il-6, Il-1, and Cd31 genes on days 2 and 7 after OT. Additionally, we measured total antioxidant capacity (TAC), malondialdehyde (MDA) levels, as well as the activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX). Our results demonstrated that NAC, PEMF, and NAC+PEMF treatments significantly increased the number of follicles. Moreover, we observed a more pronounced development of vascularization in the NAC, PEMF, and PEMF+NAC groups. The relative expression levels of Fgf-2, Vegf, Tnf-α, Il-1ß, and Il-6 were significantly elevated in the NAC, PEMF, and NAC+PEMF groups. Notably, TAC levels decreased significantly in the NAC group compared to the control group. Additionally, the MDA level showed a significant decrease in the PEMF+NAC group when compared to the other groups. Overall, the combination of NAC and PEMF exhibited a synergistic effect in promoting angiogenesis and protecting against oxidative stress and inflammation during OT.

Study of quercetin and fisetin synergistic effect on breast cancer and potentially involved signaling pathways.

Naturally-derived drugs have drawn much attention in recent decades. Efficiency, lower toxicity, and economic reasons are some of their advantages that justify this broad range of administration for different diseases, including cancer. If we can find a specific combination that boosts the effects of their single therapy, leading to synergism effect, increased efficiency, and decreased toxicity, they can act even better. Quercetin and fisetin, two well-known flavonoids, have been used to fight against various cancers. In this study, we investigated their possible synergism quercetin and fisetin on MCF7, MDA-MB-231, BT549, T47D, and 4T1 breast cancer cell lines. Then the optimum combined dose was used to study their impacts on wound healing abilities and clonogenic properties. The real-time qPCR was used to study the expression of their validated downstream effectors in predicted pathways. A significant synergism effect (p < .01, combination index: <1) was observed for all cell lines. Combination therapy was significantly more effective in colony formation (p < .0001) and wound healing assays (p < .001) compared to single therapies. The expression level of potential effectors was also showed a greater change. In vivo study confirmed the in vitro results and showed how significantly (p < .001) their synergism promotes their singular function in inhibiting cancer progression. The breast cancer mouse models receiving combined therapy lived longer with higher average body weight and smaller tumor sizes. These results exhibit that quercetin and fisetin inhibit cancer cell proliferation, migration and colony formation synergistically, and matrix metalloproteinase signaling and apoptotic pathways are relatively responsible for inhibitory activities.

Osteogenic effect of electromagnetic fields on stem cells derived from rat bone marrow cultured in osteogenic medium versus conditioned medium in vitro.

OBJECTIVES: This study assessed possible osteogenic differentiation caused by electromagnetic fields (EMF) on rat bone-marrow-derived stem cells (rBMSCs) cultured in osteogenic medium (OM) or in human adipose-stem cell-conditioned medium (hADSC-CM). MATERIALS AND METHODS: The rBMSCs were divided into negative and positive control groups, cultured in α-MEM plus 10% FBS or OM respectively. CM and CM + EMF  groups, cultured cells in hADSCs-CM or exposed to EMF (50 Hz, 1 mT) for 30 min/day plus hADSCs-CM, respectively. Cells from the OM + EMF were simultaneously cultured in OM and exposed to EMF. Osteogenesis was investigated through alkaline phosphatase activity, alizarin red staining and real-time PCR. RESULTS: A meaningfully higher level of ALP activity was observed in the OM + EMF group compared to the other groups. There was a considerable increase in Runx2 expression in the CM + EMF group compared to the positive control and CM groups and a significant increase in Runx2 expression in the OM + EMF in comparison with all other groups after 21 days. Runx2 expression increased significantly in the CM, CM + EMF and positive control groups on day 21 compared to the same groups on day 14. From days 14-21, Ocn expression increased in the CM and CM + EMF groups, but both groups showed a significant decrease compared to the positive controls. CM and EMF had no effect on Ocn expression. On day 21, Ocn expression was significantly higher in the OM + EMF group than in the positive control group. CONCLUSION: The synergistic effect of EMF and OM increased the expression of Runx2 and Ocn in rBMSCs.

In vitro osteogenic induction of human adipose stem cells co-treated with betaine/osteogenesis differentiation medium.

Human adipose-derived stem cells (hADSCs) are widely used in regenerative medicine and affected by many biochemical and biophysical stimuli in vivo. Betaine has been reported to be a type of osteogenic stimulating biochemical factor. This study aimed to investigate the effects of betaine; on osteogenic differentiation of cultured hADSCs in osteogenesis differentiation medium. Mesenchymal stem cells were extracted from women undergoing liposuction after obtaining written consent and cultured in vitro. The cells at passage 4 were confirmed by flow cytometry and differentiated into osteocytes and adipocytes. Experimental groups were the cells cultured in osteogenesis differentiation medium (control), cultured in α-MEM and 10% serum-containing Betaine (BET) ,and cultured in osteogenesis differentiation medium containing 10 mM Betaine (OD+BET). After 14 and 21 days of treatment, osteogenic differentiation and the expression of RUNX2 and OCN genes were assessed by qualitative and quantitative Alizarin red staining and real-time PCR. There were significant increases in the calcium matrix deposits, alkaline phosphatase activity ,and expression of RUNX2 and OCN genes in the OD+BET group compared to the BET group. At the end of day 14, the calcium matrix formation was significantly decreased the in BET group compared to the control. Treatment of hADSCs with Betaine, and osteogenesis differentiation medium leads to increased alkaline phosphatase activity, matrix calcium deposits and expression of RUNX2 and OCN genes and finally stimulated osteogenesis. This kind of treatment could be used to support bone regeneration in the future of tissue engineering.

Synergic effects of extremely low-frequency electromagnetic field and betaine on in vitro osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells.

Human adipose tissue-derived mesenchymal stem cells (hADSCs) due to easy extraction, relative abundance, in vitro expansion and differentiation potential, frozen storage capability, and ability to secrete cytokines, compared to other stem cells, are appropriate candidate in regenerative medicine. Extremely low-frequency electromagnetic fields (ELF-EMF) and betaine are two safe factors in bone lesions repair. This study was designed to assess the osteogenic differentiation potential of these factors on hADSCs. The samples were collected from women undergoing liposuction after obtaining written consent. The hADSCs were extracted and treated with osteogenesis differentiation medium (OD) as the positive control, with OD and betaine (BET group), with OD and EMF (EMF group), and with OD and betaine and EMF (BET+EMF group) for 21 d; the negative control consisted of cells without treatment. Betaine 10 mM and EMF with 50-Hz frequency, 1-mT intensity (8 h daily), and in the form of sinus wave were used. Osteogenic differentiation was evaluated by Alizarin Red staining, alkaline phosphatase activity, calcium deposition, and real-time PCR. A significant increase in calcium deposition in the BET+EMF group was observed compared to the other groups. The activity of alkaline phosphatase in the positive control and BET groups was increased significantly compared to EMF and BET + EMF groups and a significant increase of this enzyme activity in the BET + EMF compared to EMF group was observed. The expression of RUNX2 and OCN genes in the EMF-treated groups were significantly reduced compared to the non-EMF-treated groups, and BET+EMF showed a significant increase of RUNX2 gene expression as compared the EMF group. The ELF-EMF leads to a decrease in the osteogenic differentiation and the expression RUNX2 and OCN genes in hADSCs. But osteogenic differentiation and RUNX2 gene expression were increased post-induction by betaine. The synergic effect of betaine and EMF on the osteogenic differentiation and related genes expression of hADSCs was higher than EMF.

Expression of neurotrophic factor genes by human adipose stem cells post-induction by deprenyl.

Human adipose stem cells (hASCs) were introduced as appropriate candidate due to advantages like ease of isolation, in vitro expansion and lack of immune response. Deprenyl (Dep) was used to induce bone marrow stem cells into neuron-like cells. We investigated the Dep effect on neurotrophin genes expression in hASCs and their differentiation into neuron-like cells. The cells were isolated from small pieces of abdominal adipose tissue and subjected to flow cytometry to confirm purification. The osteogenic and adipogenic differentiation were identified. The proliferation rate and neurotrophin genes expression of treated cells were evaluated by MTT, TH immunostaining and RT-PCR. hASCs had positive response to CD44, CD73, CD90, CD105 markers and negative response to CD34 and CD45 markers and differentiated into adipocytes and osteocytes. Exposure to 10-7 M of Dep for 24 hours caused a significant increase of viable cells and BDNF, NTF-3 genes expression as compared to cultured cells in serum free medium and had no effect on the expression of NGF and GDNF genes. Based on our results, Dep is able to induce BDNF, NTF-3 and NTF-4 genes expression and neroun-like morphology in hASCs.

Pre-treatment by Rosemary Extract or Cell Transplantation Improves Memory Deficits of Parkinson's Disease: When Tradition Meets the Future

ABSTRACT The therapeutic effect of adipose tissue-derived stem cells (ADSCs) or RE on hippocampal neurogenesis and memory in Parkinsonian rats were investigated. Male rats were lesioned by bilateral intra-nigral injections of 6-OHDA and divided into six groups: 1. Lesion 2 and 3: RE and water groups were lesioned rats pretreated with RE or water, from 2weeks before neurotoxin injection and treated once a day for 8weeks post lesion. 4&5: Cell and α-MEM (α-minimal essential médium) received intravenous injection of BrdU-labeled ADSCs or medium, respectively from 10days post lesion until 8weeks later. 6: Sham was injected by saline instead of neurotoxin. Memory was assessed using Morris water Maze (MWM), one week before and at 1, 4 and 8weeks post 6-OHDA lesion. After the last probe, the animals were sacrificed and brain tissue obtained. Paraffin sections were stained using cresyl violet, anti-BrdU (Bromodeoxyuridine / 5-bromo-2'-deoxyuridine), anti-GFAP (Glial fibrillary acidic protein) and anti-TH antibodies. There was a significant difference of time spent in the target quadrant between groups during probe trial at 4 and 8 weeks' post- lesion. Cell and RE groups spent a significantly longer period in the target quadrant and had lower latency as compared with lesion. Treated groups have a significantly higher neuronal density in hippocampus compared to water, α-MEM and lesion groups. BrdU positive cells were presented in lesioned sites. The GFAP (Glial fibrillary acidic protein) positive cells were reduced in treated and sham groups compared to the water, α-MEM and lesion groups. Oral administration of RE (Rosemary extract) or ADSCs injection could improve memory deficit in the Parkinsonian rat by neuroprotection.

Conditioned Medium Protects Dopaminergic Neurons in Parkinsonian Rats.

OBJECTIVE: Adipose derived stem cells (ASCs) secrete numerous neurotrophic factors and cytokines in conditioned medium (CM), which protect neurons by its antioxidative and trophic effects. This research assesses the neuroprotective effect of ASCCM on neurotrophins genes expressions and tyrosine hydroxylase positive (TH+) cell density in male Wistar rats lesioned by 6-hydroxydopamine (6-OHDA). MATERIALS AND METHODS: In this experimental study, the groups consisted of lesioned and sham rats with unilateral injections of 20 µg of 6-OHDA neurotoxin and phosphate buffered saline (PBS) into the striatum, respectively. Another groups received intravenous injections of 3×106 cells (ASCs group), 500 µl of CM (ASC-CM group) or medium [α-minimal essential medium (α-MEM) group)]. All rats underwent evaluations with the rotarod and apomorphine-induced rotation tests at 2, 4, 6, and 8 weeks post-injection. At 8 weeks we sacrificed some of the animals for real-time polymerase chain reaction (PCR) analysis, and evaluation of TH+ cell counts. RESULTS: We observed a significant decrease in contralateral turns to the lesions in the ASCs and ASC-CM groups compared to the neurotoxin lesioned or α-MEM groups at 8 weeks post transplantation. Cell and CM- injected rats showed a significant increase of staying on the rotarod compared to the lesion or α-MEM groups. Cell and CM-treated rats showed significant increases in the NGF and NT3 genes, respectively, compared with the lesion group. Both treated groups showed significant increases in BDNF gene expression and TH+ cell density. CONCLUSION: The results suggested that ASCs and ASC-CM protected dopaminergic neurons through the expressions of neurotrophin genes.

Transplantation of Deprenyl-Induced Tyrosine Hydroxylase-Positive Cells Improves 6-OHDA-Lesion Rat Model of Parkinson's Disease: Behavioral and Immunohistochemical Evaluation.

OBJECTIVE: There is longstanding experimental and clinical evidence that supports the idea that replacement of dopaminergic (DAergic) neurons can ameliorate functional disabilities of Parkinson's disease (PD). The purpose of the present study is to examine the efficacy of transplantation of rat bone marrow stromal cell (BMSCs)-derived tyrosine hydroxylase-positive (TH(+)) cells induced by deprenyl into 6-hydroxydopamine (6-OHDA)-lesioned rat models, using behavioral tests and immunohistochemical evaluations. MATERIALS AND METHODS: In this experimental study, undifferentiated BrdU-labeled BMSCs were incubated in serum-free medium that contained 10(-8) M deprenyl for 24 hours. Afterwards, BMSCs were cultured for 48 hours in α-minimal essential medium (α-MEM) supplemented with 10% FBS, then differentiated into TH(+) neurons. We randomly divided 24 hemiparkinsonian rats as follows: group 1 (control) received only medium, while groups 2 and 3 were injected with 2×10(5) BMSCs and deprenyl-treated cells in 4 µl medium. Injections were made into the injured strata of the rats. Rotational behavior in response to apomorphine was tested before transplantation and at 2, 4, and 6 weeks post-graft. Animals were then sacrificed, and the brains were extracted for immunohistochemical and electron microscopic studies. RESULTS: Apomorphine-induced rotation analysis indicated that animals with grafted cells in groups 2 and 3 exhibited significantly less rotational behavior than those in the control group at 2, 4, and 6 weeks after transplantation. Immunohistochemical analysis demonstrated that BrdU-labeled cells expressed specific neuronal markers, such as NF 200 and TH, at the implantation site. The presence of TH(+) cells in conjunction with the reduction in rotation might show the capacity of grafted cells to release dopamine. Ultrastructural analysis revealed the presence of immature neurons and astrocyte-like cells at the graft site. CONCLUSION: TH(+) neurons induced by deprenyl can be considered as a cell source for PD autograft therapy.

Characterization of in vitro cultured bone marrow and adipose tissue-derived mesenchymal stem cells and their ability to express neurotrophic factors.

MSCs (mesenchymal stem cells) have attracted attention as a promising tool for regenerative medicine and transplantation therapy. MSCs exert neuroprotective effects by secreting a number of factors in vitro and in vivo. Similar characteristics are found in ADSCs (adipose-derived stem cells) and BMSCs (bone marrow stromal cells). Multipotent capability, easy accessibility and rapid proliferation of ADSCs have been established. Our main objective was to compare cell viability, growth rate, expression of neurotrophic factors and nestin genes in ADSCs and BMSCs. Cell doubling time and proliferation rate indicate that ADSCs has a higher proliferation rate than BMSCs. ADSCs and BMSCs express a similar pattern of CD71 and CD90 markers. Nestin immunostaining showed that ADSCs and BMSCs are immunopositive. The expression of neurotrophic factors genes in ADSCs proved similar to that of BMSCs genes. Thus adipose tissue stem cells with a high proliferation rate can express nestin and neurotrophic factor genes. Therefore ADSCs may be useful in future cell replacement therapies and help improve neurodegenerative diseases.

The effect of alpha lipoic acid on the developmental competence of mouse isolated preantral follicles.

PURPOSE: This study was designed to investigate the effect of alpha-lipoic acid (ALA) on reactive oxygen species (ROS) production, total antioxidant capacity (TAC) and developmental competence of cultured pre-antral follicles derived from mouse ovarian tissue. METHODS: Pre-antral follicles were isolated from immature mouse ovaries and were cultured in α- minimal essential medium supplemented with different concentrations (0, 50, 100, 250 and 500 uM) of ALA. Follicular growth, oocyte maturation and embryo development were evaluated. Separately, ROS and TAC were measured after 0, 24, 48, 72 and 96 h of culture with spectrofluorometery and ferric reducing/antioxidant power (FRAP) assay, respectively. RESULTS: In the presence of 100 uM ALA, developmental rates of follicles, oocytes and embryos were significantly higher than other groups (p < 0.05). At 96 h after culture, a decrease in ROS and an increase in TAC were observed in ALA group compared to control group (p < 0.05). CONCLUSION: ALA (100 uM) improves the in vitro development of follicles. This effect may be mediated by decreasing ROS concentration and increasing follicular TAC level during the culture period.

Spontaneous Expression of Neurotrophic Factors and TH, Nurr1, Nestin Genes in Long-term Culture of Bone Marrow Mesenchymal Stem Cells.

OBJECTIVE: It has been reported that rat bone marrow stromal cells (BMSCs) can be spontaneously differentiated into neural-like cells without any supplemental growth factors and/or chemical treatment after long-term culture.This study aims to determineWhether, growth factors secreted by MSCs could induce self-differentiation into neural-like cells in a long-term culture. MATERIALS AND METHODS: THIS STUDY CONSISTED OF TWO GROUPS: i. rat BMSCs (passage 5) were cultured in alfa- minimal essential medium (α-MEM) and 10% fetal bovine serum (FBS) without the addition of inducer and exchanging medium for three weeks, as the experimental group and ii.rat BMSCs (passage 5) as the control group. Each group was analysed by reverse transcriptase polymerase chain reaction (RT-PCR) to evaluate the expressions of neurotrophic factors and neural marker genes. Statistical analyses were carried out using one-way analysis of variance (ANOVA) and Tukey's multiple comparison with SPSS software (version 16). P< 0.05 was considered statistically significant. RESULTS: The experimental group (fifth passage of BMSCs) obtained from adult rats spontaneously differentiated into neural precursor cells after long-term culture. Cultured cells expressed tyrosine hydroxylase (TH), Nurr1 and nestin genes. Furthermore, some growing cells in suspension became neurosphere-like. Self-differentiated rat MSCs (SDrMSCs) expressed significantly higher levels of NGF (0.96 ± 0.16), nestin (0.63 ± 0.08), and Nurr1 (0.80 ± 0.10) genes (p<0.05). CONCLUSION: In this study, we reported that rMSCs in long-term culture underwent spontaneous transformation to neural precursors without the supplement of growth factors and specific chemicals. Cells expressed neural markers such as: TH, Nurr1, and nestin genes.