Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke

Introduction: Cell-based therapy is considered as promising strategy to cure stroke. However, employing appropriate type of stem cell to fulfill many therapeutic needs of cerebral ischemia is still challenging. In this regard, the current study was designed to elucidate therapeutic potential of epidermal neural crest stem cells (EPI-NCSCs) compared to bone marrow mesenchymal stem cells (BM-MSCs) in rat model of ischemic stroke. Methods: Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) for 45 minutes. Immediately after reperfusion, EPI-NCSCs or BM-MSCs were transplanted via intra-arterial or intravenous route. A test for neurological function was performed before ischemia and 1, 3, and 7 days after MCAO. Also, infarct volume ratio and relative expression of 15 selected target genes were evaluated 7 days after transplantation. Results: EPI-NCSCs transplantation (both intra-arterial and intravenous) and BM-MSCs transplantation (only intra-arterial) tended to result in a better functional outcome, compared to the MCAO group; however, this difference was not statistically significant. The infarct volume ratio significantly decreased in NCSC-intra-arterial, NCSC-intravenous and MSC-intra-arterial groups compared to the control. EPI-NCSCs interventions led to higher expression levels of Bdnf, nestin, Sox10, doublecortin, β-III tubulin, Gfap, and interleukin-6, whereas neurotrophin-3 and interleukin-10 were decreased. On the other hand, BM-MSCs therapy resulted in upregulation of Gdnf, β-III tubulin, and Gfap and down-regulation of neurotrophin-3, interleukin-1, and interleukin-10. Conclusion: These findings highlight the therapeutic effects of EPI-NCSCs transplantation, probably through simultaneous induction of neuronal and glial formation, as well as Bdnf over-expression in a rat model of ischemic strok

Advanced molecular approaches pave the road to a clear-cut diagnosis of hereditary retinal dystrophies.

Purpose: The aim of this study was to identify the molecular genetic basis of hereditary retinal dystrophies (HRDs) in five unrelated Iranian families. Methods: Whole exome sequencing and Sanger sequencing were performed in all families. Variants were analyzed using various bioinformatics databases and software. Results: Based on the selected strategies, we identified potentially causative variants in five families with HRDs: the novel homozygous deletion mutation c.586_589delTTTG (p.F196Sfs*56) in the TTC8 gene of family A, the novel homozygous missense mutation c.2389T>C (p.S797P) in the CRB1 gene in family B, the novel homozygous frameshift mutation c.2707dupA (p.S903Kfs*66) in the LRP5 gene in family C, the novel homozygous splice mutation c.584–1G>T in the MERTK gene in family D, and the novel homozygous missense mutation c.1819G>C (p.G607R) rs61749412 in the ABCA4 gene of family E. Conclusions: This study highlights the presence of five novel variants associated with retinal dystrophies in selected Iranian families with hereditary blindness

Isolation, Culture, and Characterization of Human Dental Pulp Mesenchymal Stem Cells

Introduction Based on previous researches, dental pulp stem cells (DPSCs) are easily accessible with limited morbidity after collection. Their embryonic origin, from neural crests, explains their multipotency. DPSCs are primarily derived from the pulp tissues of the teeth.Objective: This study was undertaken to isolate, culture, and characterize two different third molar and first premolar human dental pulp mesenchymal stem cells. Methods: To obtain DPSCs, pulp tissues were removed from human third molar and first premolar teeth. They were digested by treating with collagenase type I. The extracted cells were passaged from primary culture up to passage 8. To enumerate the cells, the specified number of the cells were seeded into 24-well culture plates and the number of cells were counted to determine the growth curves of isolated cells from both type of teeth and the population duplication time (PDT) was determined. PCR and karyotype assays were performed to determine the cell surface mesenchymal markers and demonstrate the genetic stability of DPSCs, respectively.  Results: The human DPSCs from both the third molar and the first premolar teeth were spindle-shaped in morphology. As growth curves showed, the proliferation rate of DPSCs in passage 8 among both teeth was different denoting to an increase in doubling time in the first premolar when compared to the third molar teeth. Normal karyotype of DPSCs derived from both the third molar and the first premolar teeth were exhibited. The isolated dental pulp stem cells expressed mesenchymal stem cell surface antigen. These cells were positive for CD73 but were negative for CD45 (hematopoietic stem cell marker). Conclusion: DPSCs can be an attractive candidate in regenerative medicine. As growth curves revealed, the first premolar teeth are suggested as a better source of MSC isolation. Keywords:  Dental pulp, Growth curve, Mesenchymal stem cell, Molar tooth, Premolar tooth

Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit the burden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity