Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres.

AIM: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. MATERIALS AND METHODS: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. RESULTS: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. CONCLUSION: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.

Mesenchymal stem cell-derived exosomes do not promote the proliferation of cancer cells in vitro.

Nowadays, the use of Mesenchymal stem cells (MSCs) in clinical therapies have an increased acceleration, while it constitutes two sides of yin-yang with its ameliorating effects in regenerative medicine and promoting effects in carcinogenesis. It has been shown that the treatment activities of MSCs are mediated by paracrine factors secreted. These paracrine factors are transmitting via exosomes secreted from MSCs. With the understanding of this mechanism, cell-free therapies have begun to create a new path in MSC based therapies. At this point, two sides of the yin-yang have once again become controversial. In addition, there are conflicting study results in the literature. Due to this contradiction, we have designed this study to demonstrate the role of MSCs in the carcinogenesis process and we investigated the proliferation effect of MSC-derived exosomes on cancer cell lines. Two parallel experimental setups were established, as an experimental group, the four-different epithelial cancer cell lines and Wharton's Jelly (WJ)-MSC derived exosomes were directly co-cultured with in 6 different concentrations and simultaneously in the control group cells were cultured respectively. PKH-26 labelling was performed for detection of exosome locations in co-cultures. Each group were evaluated by WST-1 and xCelligence assays for proliferation and confirmed with PCNA staining. The results were analysed with paired t-test and Newman-Keuls comparison. The relative comparison demonstrated a significant increase in the rate of proliferation only in exosome co-cultures with WJ-MSCs and it was supported by PCNA staining. Cancer cell lines in co-cultures have not shown any significant increase neither in proliferation assays nor in PCNA staining. MSCs regulate their secretions according to the microenvironment, they have more dominant regenerative feature rather than triggering cancer proliferation.

The Effect of Umbilical Cord-derived Mesenchymal Stem Cell Transplantation in a Patient with Cerebral Palsy: A Case Report.

BACKGROUND: Cerebral Palsy (CP) is the most common motor disability reason of childhood that occurs secondarily to non-progressive damage in the brain whose development is still ongoing. METHODS: 6-year-old dystonic-spastic male CP patient received allogenic mesenchymal stem cells treatment four times as 1×106/kg in intrathecal and intravenous administration of Umbilical Cord-derived mesenchymal stem cells (UC-MSCs) ways. Before and after the treatment, the patient was followed-up with FIM (Functional Independent Measurement), GMFCS (Gross Motor Function Classification System 88), Tardieu Scale, TCMS (Trunk Control Measurement Scale), MACS (Manual Ability Classification Scale), CFSS (Communication Function Classification System) for 18 months and received intensive rehabilitation. RESULTS: Improvements were observed especially in functional scales except for the Tardieu Scale, and no adverse effects were detected aside from a slight pain in the back. CONCLUSION: Wider future case studies on UC-MSCs will enable us to assess the efficacy of UC-MSCs which have positive impacts especially on functional scales.