The role of primed and non-primed MSC-derived conditioned media in neuroregeneration.

Introduction: With growing significance in nervous system repair, mesenchymal stem cell-derived conditioned media (MSCCM) have been used in cell-free therapies in regenerative medicine. However, the immunomodulatory and neuroregenerative effects of MSCCM and the influence of priming on these effects are still poorly understood. Methods: In this study, by various methods focused on cell viability, proliferation, neuron-like differentiation, neurite outgrowth, cell migration and regrowth, we demonstrated that MSCCM derived from adipose tissue (AT-MSCCM) and amniotic membrane (AM-MSCCM) had different effects on SH-SY5Y cells. Results and discussion: AT-MSCCM was found to have a higher proliferative capacity and the ability to impact neurite outgrowth during differentiation, while AM-MSCCM showed more pronounced immunomodulatory activity, migration, and re-growth of SH-SY5Y cells in the scratch model. Furthermore, priming of MSC with pro-inflammatory cytokine (IFN-γ) resulted in different proteomic profiles of conditioned media from both sources, which had the highest effect on SH-SY5Y proliferation and neurite outgrowth in terms of the length of neurites (pAT-MSCCM) compared to the control group (DMEM). Altogether, our results highlight the potential of primed and non-primed MSCCM as a therapeutic tool for neurodegenerative diseases, although some differences must be considered.

Stem cells in central nervous system diseases: Promising therapeutic strategies.

Central nervous system (CNS) diseases are a leading cause of death and disability. Due to CNS neurons have no self-renewal and regenerative ability as they mature, their loss after injury or disease is irreversible and often leads to functional impairments. Unfortunately, therapeutic options for CNS diseases are still limited, and effective treatments for these notorious diseases are warranted to be explored. At present, stem cell therapy has emerged as a potential therapeutic strategy for improving the prognosis of CNS diseases. Accumulating preclinical and clinical evidences have demonstrated that multiple molecular mechanisms, such as cell replacement, immunoregulation and neurotrophic effect, underlie the use of stem cell therapy for CNS diseases. However, several issues have yet to be addressed to support its clinical application. Thus, this review article aims to summarize the role and underlying mechanisms of stem cell therapy in treating CNS diseases. And it is worthy of further evaluation for the potential therapeutic applications of stem cell treatment in CNS disease.

The extract based on the Kampo formula daikenchuto (Da Jian Zhong Tang) induces Bdnf expression and has neurotrophic effects in cultured cortical neurons.

Reductions in brain-derived neurotrophic factor (BDNF) expression levels have been reported in the brains of patients with neurological disorders such as Alzheimer's disease. Therefore, upregulating BDNF and preventing its decline in the diseased brain could help ameliorate neurological dysfunctions. Accordingly, we sought to discover agents that increase Bdnf expression in neurons. Here, we screened a library of 42 Kampo extracts to identify those with the ability to induce Bdnf expression in cultured cortical neurons. Among the active extracts identified in the screen, we focused on the extract based on the Kampo formula daikenchuto. The extract of daikenchuto in the library used in this study was prepared using the mixture of Zingiberis Rhizoma Processum (ZIN), Zanthoxyli Piperiti Pericarpium (ZAN), and Ginseng Radix (GIN) without Koi. In this study, we defined DKT as the mixture of ZIN, ZAN, and GIN without Koi (DKT extract means the extract prepared from the mixture of ZIN, ZAN, and GIN without Koi). DKT extract significantly increased endogenous Bdnf expression by mediated, at least in part, via Ca2+ signaling involving L-type voltage-dependent Ca2+ channels in cultured cortical neurons. Furthermore, DKT extract significantly improved the survival of cultured cortical neurons and increased neurite complexity in immature neurons. Taken together, our findings suggest that DKT extract induces Bdnf expression and has a neurotrophic effect in neurons. Because BDNF inducers are expected to have therapeutic potential for neurological disorders, re-positioning of Kampo formulations such as daikenchuto may lead to clinical application in diseases associated with reduced BDNF in the brain.

Anti-Inflammatory, Neurotrophic, and Cytotoxic Oxylipins Isolated from Chaenomeles sinensis Twigs.

Oxylipins are important biological molecules with diverse roles in human and plants such as pro-/anti-inflammatory, antimicrobial, and regulatory activity. Although there is an increasing number of plant-derived oxylipins, most of their physiological roles in humans remain unclear. Here, we describe the isolation, identification, and biological activities of four new oxylipins, chaenomesters A-D (1-4), along with a known compound (5), obtained from Chaenomeles sinensis twigs. Their chemical structures were determined by spectroscopic (i.e., NMR) and spectrometric (i.e., HRMS) data analysis including 1H NMR-based empirical rules and homonuclear-decoupled 1H NMR experiments. Chaenomester D (4), an omega-3 oxylipin, showed a potent inhibitory effect on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells (NO production, 8.46 ± 0.68 µM), neurotrophic activity in C6 cells through the induction of the secretion of nerve growth factor (NGF, 157.7 ± 2.4%), and cytotoxicity in A549 human cancer cell lines (IC50 = 27.4 µM).

Imaging Analysis of Neurotrophic Effects by CCN2 Protein in Neuronal Precursor Cells Derived from Human-Induced Pluripotent Stem Cells.

Human-induced pluripotent stem cells (hiPSCs) are useful tools to examine human neuronal maturation processes. In this chapter, we describe the maturation of human neuronal precursor cells derived from hiPSCs by cellular communication network family member 2, also known as connective tissue growth factor. We describe the (1) preparation of feeder cells for undifferentiated culture of hiPSCs, (2) undifferentiated culture of hiPSCs, (3) induction of neuronal precursor cells from hiPSCs, (4) maturation of neuronal precursor cells from hiPSCs, (5) immunofluorescent staining of neuronal cells from hiPSCs, and (6) immunofluorescence analysis.

Terpenoids from Glechoma hederacea var. longituba and their biological activities.

Glechoma hederacea var. longituba (common name: ground ivy) has been used for the treatment of asthma, bronchitis, cholelithiasis, colds, and inflammation. In the present study, three new sesquiterpene glycosides (1-3), two new diterpene glycosides (4 and 5), and four known compounds (6-9) were isolated from its MeOH extract. A structure elucidation was performed for the five new compounds (1-5) using 1D and 2D NMR, HRESIMS, DP4+ and ECD calculations, and chemical methods. All the isolates (1-9) were assessed for their antineuroinflammatory activities on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, nerve growth factor (NGF) secretion stimulation activities in C6 glioma cells, and cytotoxic activities against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 2 and 5-7 exhibited inhibitory effects on the NO production with IC50 values of 52.21, 47.90, 61.61, and 25.35 µM, respectively. Compound 5 also exhibited a significant stimulating effect on NGF secretion (122.77 ± 8.10%). Compound 9 showed potent cytotoxic activity against SK-OV-3 (IC50 = 3.76 µM) and SK-MEL-2 (IC50 = 1.48 µM) cell lines, while 7 displayed a strong cytotoxic activity against the SK-MEL-2 (IC50 = 9.81 µM) cell line.

Therapeutic Effect of Human Mesenchymal Stem Cell-Conditioned Medium on Erectile Dysfunction.

PURPOSE: Owing to the safety and cost effectiveness of conditioned medium (CM), its therapeutic effects have attracted significant attention from many researchers. To date, numerous studies have been conducted on CM; however, little has been done with regard to erectile dysfunction (ED). In this research, the potential of human mesenchymal stem cell-derived CM (MSC-CM) for the treatment of ED was investigated. MATERIALS AND METHODS: A high concentration of MSC-CM was prepared through 3D spheroid culturing with bone marrow-derived MSCs and cut-off filtering. The composition of CM was analyzed using biochemical assays, and the effect of the preparation process on the quality of CM was investigated. The therapeutic effects of MSC-CM were evaluated through animal studies using a cavernous nerve (CN) injury rat model. RESULTS: 3D spheroid culturing afforded a 278-fold increase in the total protein content of CM, as compared to that from 2D cultures; the protein concentration increased by 19 times on increasing the centrifugation time for cut-off filtering. Biochemical assays indicated that the CM contains various types of angiogenic, neurotrophic, and anti-inflammatory factors. Histological assay results showed that MSC-CM has angio- and neuro-trophic effect in a CN injury rat model in vivo, and these therapeutic effects appear in a dose-dependent manner. CONCLUSIONS: The experimental results confirmed the therapeutic effect of MSC-CM in healing damaged cavernosal tissue and restoring erectile function. These results successfully demonstrated that MSC-CM has significant potential for the treatment of ED.

Glycosylated constituents isolated from the trunk of Abies holophylla and their anti-inflammatory and neurotrophic activity.

Eleven previously undescribed glycosylated compounds with phenolic (abeoside A-F), monoterpenyl (abeoside G and H), or 2-heptanyl (abeoside I-K) aglycone, and twenty one reported compounds were isolated from the trunk of Abies holophylla. The structures of the previously undescribed compounds were elucidated on the basis of the conventional NMR and HRMS data analysis, and the absolute configuration of sugar units were assigned by chiral derivatization and LC-MS analysis. All the isolated compounds were evaluated for their anti-neuroinflammatory and neurotrophic activities. Among the evaluated compounds, twelve compounds including abeoside A, B, E, G, H, J, and K exhibited strong anti-neuroinflammatory activities with IC50 values of 4.6-18.2 µM by inhibiting production of LPS-induced NO levels, and abeoside C and 1-O-[(S)-oleuropeyl]-ß-D-glucoside showed powerful effects on the stimulation of NGF secretion levels with 157.09 ± 8.53% and 154.74 ± 1.24%, respectively.

[Neurobiological effects of tenuigenin and the opportunity of it's using in the therapy of Alzheimer's and Parkinson's diseases (literature review).]

The analysis of experimental and partially clinical data about researches of neurobiological effects of tenuigenin - the most important bioactive substance of Polygala tenuifolia Willd. in this review was given. The neuroprotective and neurotrophic action of given substance were described in detail. It was noted, that the capacities of the tenuigenin to decrease the secretion of beta amyloid and to protect of neurons from damage by already made beta ameloids, to inhibit the processes of the tau proteins` hyperphosphorylation and inflammations in microglia, as well as increase the main synaptic transmission can be used by the development of effective therapeutic drugs aimed to reduce the pathogenesis of Alzheimer`s disease. The effects of dopaminergic neurons and mitochondrial membrane potential protection as well as reduction of α-synuclein phosphorylation can influence the processes by Parkinson`s disease. It was concluded, that the tenuigenin deserves further study and possibly will be used as augmentation of Alzheimer`s, Parkinson`s and other neurodegenerative diseases therapy.

The antibiotic doxycycline mimics the NGF signaling in PC12 cells: A relevant mechanism for neuroprotection.

Doxycycline has been used as antibiotic since the 1960s. Recently, studies have shown that doxycycline is neuroprotective in models of neurodegenerative diseases and brain injuries, mainly due to anti-inflammatory and anti-apoptotic effects. However, it is not known if doxycycline has neurotrophic potential, which is relevant, considering the role of axonal degeneration at the early stages of neurodegeneration in Alzheimer's disease, Amyotrophic Lateral Sclerosis and Parkinson's disease as well as in normal aging. Axons are preceded by the formation of neurites, the hallmark of the neuronal differentiation induced by neurotrophins like NGF. Therefore, the modulation of neurotrophin receptors aimed at formation and regeneration of axons has been proposed as a strategy to delay the progression of neurodegeneration and has gained relevance as new techniques for early diagnosis arise. Based on these premises, we investigated the potential of doxycycline to mimic the effects of Nerve Growth Factor (NGF) with focus on the signaling pathways and neuronal modulators of neurite initiation, growth and branching. We used PC12 cells, a neuronal model widely employed to study the neurotrophic pathways and mechanisms induced by NGF. Results showed that doxycycline induced neurite outgrowth via activation of the trkA receptor and the downstream signaling pathways, PI3K/Akt and MAPK/ERK, without inducing the expression of NGF. Doxycycline also increased the expression of GAP-43, synapsin I and NF200, proteins involved in axonal and synaptic plasticity. Altogether, these data demonstrate, for the first time, the neurotrophic potential of doxycycline, which might be useful to restore the neuronal connectivity lost at the initial phase of neurodegeneration.

Phenolic Constituents of Chinese Quince Twigs (Chaenomeles sinensis Koehne) and Their Anti-Neuroinflammatory, Neurotrophic, and Cytotoxic Activities.

Chaenomeles sinensis has been used as a food and traditional medicines. However, most of research on discovering bioactive constituents from this plant have been focused on its yellow fruit, Chinese quince, due to its wide usage. Here, we isolated and characterized three new phenolic compounds (1, 9, and 11) and 21 known compounds (2-8, 10, and 12-24) from the twigs of C. sinensis. Their chemical structures were established by spectroscopic and spectrometric data analysis including 1D and 2D NMR, high-resolution mass spectrometry (HRMS), electronic circular dichroism (ECD), and LC-MS analysis. Some of the isolated compounds (1-24) showed anti-neuroinflammatory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, neurotrophic activity in C6 cells through the secretion of nerve growth factor (NGF) and/or cytotoxicity against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, MKN-1).

The Neurotrophic-Like Effect of Carvacrol: Perspective for Axonal and Synaptic Regeneration.

Carvacrol (CARV) is a phytochemical widely used as flavoring, preservative, and fragrance in food and cosmetic industries. CARV is able to cross the blood-brain barrier (BBB) and has demonstrated protective potential against neurodegenerative diseases by several mechanisms, including antioxidant, anti-inflammatory, anticholinesterase, and antiapoptotic effects. However, it is not known whether CARV is able to modulate axonal and synaptic plasticity, crucial events in cognition, memory, and learning. Abnormalities in axonal and synaptic plasticity, low levels of neurotrophins, and bioenergetic failure have been associated with the pathogenesis of neurodegenerative diseases, including Parkinson's (PD) and Alzheimer's diseases (ADs). Small lipophilic molecules with neurotrophic activity might be able to restore the axonal and synaptic networks that are lost in neurodegenerative processes. Therefore, this study investigated the neurotrophic potential of CARV in PC12 cell-based neuronal model. Carvacrol induced neurite outgrowth by activating the NGF high-affinity trkA receptor and the downstream PI3K-AKT and MAPK-ERK pathways, without depending on NGF. In addition, CARV increased the expression of proteins involved in neuronal plasticity (ß-tubulin III, F-actin, 200-kDa neurofilament, GAP-43 and synapsin-I) and improved bioenergetics (AMPKα, p-AMPKα, and ATP). Our study showed, for the first time, a promising neurotrophic mechanism of CARV that could be beneficial in neurodegenerative and neurological diseases.

Characterizing gangliosides in six sea cucumber species by HILIC-ESI-MS/MS.

An HILIC-ESI-MS/MS method was established to analyze ganglioside (GLS) in sea cucumbers. In total, 17 GLS subclasses were detected in six sea cucumber species. The basic sea cucumber GLSs (SC-GLSs) were elucidated as NeuGc2-6Glc1-1Cer (SC-GM4). The polymerization degree of the sialic acid (Sia) of SC-GLSs can be up to 4, and the linkage among Sias was mostly determined to be 2-8 or 2-11. Neu5Gc, sulfated and fucosylated NeuGc prevalently existed in SC-GLSs. Moreover, a new SC-GLSs structure with phosphoinositidyled Sia was first observed in Bohadschia marmorata. For the first time, we demonstrated that the content of SC-GD4, which is the dominant GLS in sea cucumbers, was 27-67%. Minor GLSs characterized as SC-GT2(Neu5GcMe) and SC-GQ2(Neu5GcMe) were also discovered. Additionally, SC-GD4 and SC-GD4(1S) could significantly promote the differentiation of PC12 cells with structure-selectivity (p < 0.05). Our results provide insights into SC-GLSs to elucidate their Sia substituent and core saccharide chain linkage.

Reversal of Age-Related Neuronal Atrophy by α5-GABAA Receptor Positive Allosteric Modulation.

Aging is associated with reduced brain volume, altered neural activity, and neuronal atrophy in cortical-like structures, comprising the frontal cortex and hippocampus, together contributing to cognitive impairments. Therapeutic efforts aimed at reversing these deficits have focused on excitatory or neurotrophic mechanisms, although recent findings show that reduced dendritic inhibition mediated by α5-subunit containing GABA-A receptors (α5-GABAA-Rs) occurs during aging and contributes to cognitive impairment. Here, we aimed to confirm the beneficial effect on working memory of augmenting α5-GABAA-R activity in old mice and tested its potential at reversing age-related neuronal atrophy. We show that GL-II-73, a novel ligand with positive allosteric modulatory activity at α5-GABAA-R (α5-PAM), increases dendritic branching complexity and spine numbers of cortical neurons in vitro. Using old mice, we confirm that α5-PAM reverses age-related working memory deficits and show that chronic treatment (3 months) significantly reverses age-related dendritic shrinkage and spine loss in frontal cortex and hippocampus. A subsequent 1-week treatment cessation (separate cohort) resulted in loss of efficacy on working memory but maintained morphological neurotrophic effects. Together, the results demonstrate the beneficial effect on working memory and neurotrophic efficacy of augmenting α5-GABAA-R function in old mice, suggesting symptomatic and disease-modifying potential in age-related brain disorders.

Growth hormone (GH) and synaptogenesis.

Growth hormone (GH) is known to exert several roles during development and function of the nervous system. Initially, GH was exclusively considered a pituitary hormone that regulates body growth and metabolism, but now its alternative extrapituitary production and pleiotropic functions are widely accepted. Through excess and deficit models, the critical role of GH in nervous system development and adult brain function has been extensively demonstrated. Moreover, neurotrophic actions of GH in neural tissues include pro-survival effects, neuroprotection, axonal growth, synaptogenesis, neurogenesis and neuroregeneration. The positive effects of GH upon memory, behavior, mood, sensorimotor function and quality of life, clearly implicate a beneficial action in synaptic physiology. Experimental and clinical evidence about GH actions in synaptic function modulation, protection and restoration are revised in this chapter.

Chemical constituents of Chaenomeles sinensis twigs and their biological activity.

A new megastigmane-type norsesquiterpenoid glycoside, chaemeloside (1), was isolated from the twigs of Chaenomeles sinensis together with 11 known phytochemicals through chromatographic methods. The chemical structure of the new isolate 1 was determined by conventional 1D and 2D NMR data analysis, ECD experiment, hydrolysis followed by a modified Mosher's method, and LC-MS analysis. The characterized compounds' biological effects including cytotoxicity against cancer cell lines, antineuroinflammatory activity, and potential neurotrophic effect were evaluated.

Preparation and effects on neuronal nutrition of plasmenylethonoamine and plasmanylcholine from the mussel Mytilus edulis.

Plasmenylethonoamine (pPE) and plasmanylcholine (aPC) are important phospholipid subclasses. Herein we explored optimum conditions for enzymatic purification and preparation of pPE and aPC from the mussel Mytilus edulis and bovine brain. Among them, pPE in Mytilus edulis PE was mainly p18:0-20:5 and p18:0-22:6, and its purity was 92.7%; aPC in PC was primarily a16:0-22:6 and a16:0-20:5, and aPC accounted for 90.2% of PC. We thereafter evaluated neurotrophic effects of Mytilus edulis pPE, aPC, and bovine brain pPE in a NGF-induced PC12 cell model. Morphologically, pPE and aPC could both promote differentiation, manifested in a significant increase in neurite length and number, due to increased expression of synaptophysin and growth protein GAP-43 in a dose-independent and structure-selective manner. Importantly, the effect on neuronal nutrition of pPE was better than aPC, and marine pPE was better than terrestrial pPE, which might be ascribed to vinyl-ether bond and differences in fatty acid composition.Abbreviations: AA: arachidonic acid; DHA: docosahexaenoic acid; EIC: extracted ion chromatogram; EPA: eicosapentanoic acid; GAP: growth-associated protein; HPLC: high-performance liquid chromatography; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LPC: lyso-PC; LPE: lyso-PE; MS: mass spectrometry; NGF: nerve growth factor; PC: phosphatidylcholine; aPC: plasmanylcholine; PE: phosphatidylethanolamine; pPE: plasmenylethonoamine; PG: phosphoglycerols; PLs: phospholipids; PS: phosphoserines; TIC: total ion chromatogram.

Olfactory Ensheathing Cells express both Ghrelin and Ghrelin Receptor in vitro: a new hypothesis in favor of a neurotrophic effect.

Olfactory Ensheathing Cells (OECs) are glial cells able to secrete different neurotrophic growth factors and thus promote axonal growth, also acting as a mechanical support. In the olfactory system, during development, they drive the non-myelinated axons of the Olfactory Receptor Neurons (ORNs) towards the Olfactory Bulb (OB). Ghrelin (Ghre), a gut-brain peptide hormone, and its receptor (GHS-R 1a) are expressed in different parts of the central nervous system. In the last few years, this peptide has stimulated particular interest as results show it to be a neuroprotective factor with antioxidant, anti-inflammatory and anti-apoptotic properties. Our previous studies showed that OB mitral cells express Ghre, thus being able to play an important role in regulating food behavior in response to odors. In this study, we investigated the presence of Ghre and GHS-R 1a in primary mouse OECs. The expression of both Ghre and its receptor was assessed by an immunocytochemical technique, Western Blot and Polymerase Chain Reaction (PCR) analysis. Our results demonstrated that OECs are able to express both Ghre and GHS-R 1a and that these proteins are detectable after extensive passages in vitro; in addition, PCR analysis further confirmed these data. Therefore, we can hypothesize that Ghre and GHS-R 1a interact with a reinforcement function, in the peripheral olfactory circuit, providing a neurotrophic support to the synaptic interaction between ORNs and mitral cells.

2-Iodo-4'-Methoxychalcone Attenuates Methylglyoxal-Induced Neurotoxicity by Activation of GLP-1 Receptor and Enhancement of Neurotrophic Signal, Antioxidant Defense and Glyoxalase Pathway.

Methylglyoxal (MG) acts as a reactive precursor of advanced glycation end products (AGEs). This compound is often connected with pathologies such as diabetes, neurodegenerative processes and diseases of aging. 2-iodo-4'-methoxychalcone (CHA79), a synthetic halogen-containing chalcone derivative, has been reported its anti-diabetic activity. This study aims to investigate the potential protective capability of CHA79 against MG-mediated neurotoxicity in SH-SY5Y cells. Results indicated CHA79 increased viability of cells and attenuated the rate of apoptosis in MG-exposed SH-SY5Y. CHA79 up-regulated expression of anti-apoptotic protein (Bcl-2) and down-regulated apoptotic proteins (Bax, cytochrome c, caspase-3, caspase-9). Moreover, CHA79 significantly up-regulated expression of neurotrophic factors, including glucagon-like peptide-1 receptor (GLP-1R), brain derived neurotrophic factor (BDNF), p75NTR, p-TrkB, p-Akt, p-GK-3ß and p-CREB. CHA79 attenuated MG-induced ROS production and enhanced the antioxidant defense including nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, SOD and GSH. Furthermore, CHA79 attenuated MG-induced reduction of glyoxalase-1 (GLO-1), a vital enzyme on removing AGE precursors. In conclusion, CHA79 is the first novel synthetic chalcone possessing the GLP-1R and GLO-1 activating properties. CHA 79 also exhibits neuroprotective effects against MG toxicity by enhancing neurotrophic signal, antioxidant defense and anti-apoptosis pathway.

Protective effect of human umbilical cord mesenchymal stem cells on light-damaged retinal pigment epithelial cells / 中华实验眼科杂志

Objective@#To investigate the protective effect of human umbilical cord mesenchymal stem cells (UCMSCs) on light-damaged retinal pigment epithelial (RPE) cells in vitro.@*Methods@#Human UCMSCs were cultured, and then identified by flow cytometry.Human RPE cells were isolated and cultured, and then the model of light-damaged RPE cells was prepared.The noncontact co-culture system of light-damaged RPE cells and UCMSCs was established by Transwell chamber.RPE cells were divided into normal control group, model control group and UCMSCs co-culture group.RPE cells in the normal control group were not treated.RPE cells in the model control group were treated with blue light to induce RPE cell damage.Co-culture system of light-damaged RPE cells and UCMSCs was established in the UCMSCs co-culture group.The proliferative ability of RPE cells was measured by methyl thiazolyl tetrazolium (MTT) assay at 24 hours and 48 hours after co-culture.ELISA kits were used to quantitatively measure the levels of pigment epithelium-derived factor (PEDF) and basic fibroblast growth factor (bFGF) in the culture supernatant at 48 hours after co-culture.And the photoreceptor outer segments (POS) phagocytosis assay of RPE cells was also conducted.@*Results@#UCMSCs displayed spindle-shaped morphology, positively expressed CD29, CD44, CD90 and CD105, while negatively expressed CD34 and CD45.RPE cells were polygonal in morphology and positive for the specific marker RPE65 protein.The proliferative ability(A value) of RPE cells in the three groups at different timepoints were significantly different (Fgroup=132.388, P=0.000; Ftime=231.440, P=0.000), the A values of RPE cells in model control group and UCMSCs co-culture group were significantly lower than that in the normal control group, the A value of RPE cells in UCMSCs co-culture group was significantly higher than that in the model control group, and the differences were statistically significant both at 24 hours and 48 hours after co-culture (all at P<0.01). POS phagocytosis test showed that there was a significant difference in the average number of POS particles phagocytized by RPE cells among the three groups(F=28.087, P=0.000). The average number of POS particles phagocytized by RPE cells in model control group was significantly lower than that in normal control group, and the average number of POS particles phagocytized by RPE cells in UCMSCs co-culture group was significantly more than that in model control group (all at P<0.01). ELISA showed that the concentrations of PEDF in RPE cell supernatant of normal control group, model control group and UCMSCs co-culture group were (18.8±1.9), (10.0±1.7) and (20.2±6.0)ng/ml, respectively.The concentrations of bFGF in RPE cell supernatant were (25.2±1.5), (26.3±3.6) and (61.9±14.3)pg/ml, respectively.There were significant differences in PEDF and bFGF concentrations among the three groups (F=8.654, P=0.008; F=23.698, P=0.000). The concentration of PEDF in the model control group was significantly lower than that in the normal control group, and the concentration of PEDF in the UCMSCs co-culture group was significantly higher than that in the model control group (all at P<0.01). The concentration of bFGF in UCMSCs co-culture group was significantly higher than that in the normal control group and model control group (all at P<0.01).@*Conclusions@#Cocultivation with UCMSCs can improve the proliferation ability and phagocytosis function of light-damaged RPE cells, and promote the secretion of PEDF by RPE cells.UCMSCs may protect RPE cells from light damage through paracrine secretion of bFGF.