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A neurological disorder is any disorder or abnormality in the nervous system. Among different neurological disorders, Alzheimer's disease (AD) is recognized as the sixth leading cause of death globally. Considerable research has been conducted to find pioneer treatments for this devastating disorder among which cell therapy has attracted remarkable attentions over the last decade. Up to now, targeted differentiation into specific desirable cell types has remained a major obstacle to clinical application of cell therapy. Also, potential risks including uncontrolled growth of stem cells could be disastrous. In our novel protocol, we used basal forebrain cholinergic progenitor cells (BFCN) derived from human chorion-derived mesenchymal stem cells (hC-MSCs) which made it possible to obtain high-quality population of cholinergic neurons and in vivo in much shorter time period than previous established methods. Remarkably, the transplanted progenitors fully differentiated to cholinergic neurons which in turn integrated in higher cortical networks of host brains, resulting in significant improvement in cognitive assessments. This method may have profound implications in cell therapies for any other neurodegenerative disorders. Graphical Abstract ᅟ.

Objective: Skin wound healing is a serious clinical problem especially after surgery and severe injury of the skin. Cell therapy is an innovative technique that can be applied to wound healing. One appropriate source of stem cells for therapeutic use is stem cells from the adult bulge of hair follicles. This study examined the effects of adult bulge hair follicle stem cells (HFSC) in wound healing., Materials and Methods: Hair follicle stem cells were obtained from rat vibrissa and labeled with DiI (Invitrogen, Carlsbad, CA), then special markers were detected using flow cytometry. A full-thickness excisional wound model was created and DiI-labeled HFSC were injected around the wound bed. Wound healing was recorded with digital photographs. Animals were sacrificed at 3, 7, or 14 days after surgery, and were used for the following histological analyses., Results: Flow cytometry analysis showed that HFSC were CD34 positive and nestin positive, but K15 negative. Morphological analysis of HFSC-treated wounds exhibited accelerated wound closure. Histological analysis of hematoxylin and eosin stained and Masson's trichrome-stained photomicrographs showed significantly more re-epithelialization and dermal structural regeneration in HFSC-treated wounds than in the control group. Immunohistochemical analysis of CD31 protein-positive cells showed angiogenesis was also more significant in HFSC-treated wounds than in the control group., Conclusion: Hair follicle stem cells accelerate skin wound healing. Isolating HFSC from a small skin biopsy could repair less-extensive full-thickness skin wounds by autologous stem cells and overcome major challenges regarding the use of stem cells in clinical application, while avoiding immune rejection and ethical concerns.

Metabolic diabetes mellitus as the most serious and prevalent metabolic disease in the world has various complications. The most effective treatment of type I diabetes seems to be islet cell transplantation. Shortage of donors and difficult procedures and high rate of rejection have always restricted this approach. Tissue engineering is a novel effective solution to many medical problems such as diabetes. Endometrial mesenchymal stem cells as a lineage which have the potential to differentiate to mesodermal and endodermal tissues seem to be suitable for this purpose. Fibrin hydrogel with a high degree of biocompatibility and specific properties making it similar to normal pancreas seems to be an ideal scaffold. After successfully isolating stem cells (hEnSCs) from human endometrium, a three-step protocol was used to differentiate them into pancreatic beta cells. Fibrin was used as 3D scaffold. After 2 weeks, cells formed clusters like islets cells, and secretion of insulin was measured by chemiluminescence. PDX1, proinsulin, and c-peptide as special markers of β cells were detected by immunofluorescence. Expression of glucagon, PDX1, and insulin genes in mRNA level was detected by Real time PCR and gel electrophoresis. The former showed higher levels of gene expression in 3D cultures. SEM analysis showed good integrity between cells and scaffold. No toxicity was detected with fibrin scaffold by MTT assay., (© 2014 International Federation for Cell Biology.)

Introduction: Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage Methods: OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Results: Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brainderived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after cocultured with PC12, the mean neurite length was enhanced by OE-MSCs. Conclusion: The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage. OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis (IPF) is among the illnesses with a high mortality rate, yet no specific cause has been identified; as a result, successful treatment has not been achieved. Among the novel approaches for treating such hard-to-cure diseases are induced pluripotent stem cells (IPSCs). Some studies have shown these cells' potential in treating IPF. Therefore, we aimed to investigate the impact of IPSCs on insulin-like growth factor (Igf) signaling as a major contributor to IPF pathogenesis.  C57BL/6 mice were intratracheally instilled with Bleomycin (BLM) or phosphate-buffered saline; the next day, half of the bleomycin group received IPSCs through tail vein injection. Hydroxyproline assay and histologic examinations have been performed to assess lung fibrosis. The gene expression was evaluated using specific primers for Igf-1, Igf-2, and insulin receptor substrate 1 (Irs-1) genes and SYBR green qPCR master mix. The data have been analyzed using the 2-ΔΔCT method. The mice that received Bleomycin showed histological characteristics of the fibrotic lung injury, which was significantly ameliorated after treatment with IPSCs comparable to the control group. Furthermore, gene expression analyses revealed that in the BLM group, Igf1, Igf2, and Irs1 genes were significantly upregulated, which were returned to near-normal levels after treatment with IPSCs. IPSCs could modulate the bleomycin-induced upregulation of Igf1, Igf2, and Irs1 genes. This finding reveals a new aspect of the therapeutic impact of the IPSCs on IPF, which could be translated into other fibrotic disorders. [ABSTRACT FROM AUTHOR]

Background Although stem cell therapy has become a major focus as a new option for management of spinal cord injury (SCI), its effectiveness should be promoted. In this study, we investigated the effects of co-administrating human adipose-derived stem cells (hADSCs) and Chondroitinase ABC (ChABC) in a rat model of spinal cord injury. Material and methods hADSCs derived from superficial layer of abdominal adipose tissue were used to treat a contusion-induced SCI. Animals were randomly allocated to five equal groups including sham (only laminectomy), SCI (SCI + vehicle injection), hADSCs (1 × 10⁶ hADSCs/10 μl intra-spinal injection), ChABC (10 μl of 100 U/ml ChABC intra-spinal injection injection), and hADSCs + ChABC. Basso, Beattie and Bresnahan tests were used to evaluate locomotor function. 8 weeks after treatment, cavity size, myelination, cell differentiation (neuron and astrocyte), and chondroitin sulfate amount were analyzed. Results hADSC transplanted animals, ChABC injected animals (P < 0.001), and hADSC + ChABC treated rats (P < 0.001) displayed significant motor improvement compared to SCI group. Combination therapy of hADSCs and ChABC led to greater locomotor recovery compared to using hADSCs (P < 0.001) or ChABC (P < 0.01) alone. Spinal cords in the combined and single therapy groups had cavities filled with myelinated areas and less chondroitin sulfate content in comparison with the control group (P < 0.001). hADSCs expressed GFAP, B III tubulin and Map2. Conclusion Combination therapy with ChABC and hADSCs exhibits more significant functional recovery than single therapy using either. This result may be applicable in selection of the best therapeutic strategy for SCI. [ABSTRACT FROM AUTHOR]

Objective: Tumor necrosis factor-alpha (TNF-α), checkpoint inhibitors, and interleukin-17 (IL-17) are critical targets in inflammation and autoimmune diseases. Monoclonal antibodies (mAbs) have a successful portfolio in the treatment of chronic diseases. With the current progress in stem cells and gene therapy technologies, there is the promise of replacing costly mAbs production in bioreactors with a more direct and cost-effective production method inside the patient's cells. In this paper we examine the results of an investigational assessment of secukinumab gene therapy. Materials and Methods: In this experimental study, the DNA sequence of the heavy and light chains of secukinumab antibodies were cloned in a lentiviral vector. Human chorionic villous mesenchymal stem cells (CMSCs) were isolated and characterized. After lentiviral packaging and titration, part of the recombinant viruses was used for transduction of the CMSCs and the other part were applied for systemic gene therapy. The engineered stem cells and recombinant viruses were applied for ex vivo and in vivo gene therapy, respectively, in different groups of rat models. In vitro and in vivo secukinumab expression was confirmed with quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and ELISA by considering the approved secukinumab as the standard reference. Results: Cell differentiation assays and flow cytometry of standard biomarkers confirmed the multipotency of the CMSCs. Western blot and qRT-PCR confirmed in vitro gene expression of secukinumab at both the mRNA and protein level. ELISA testing of serum from treated rat models confirmed mAb overexpression for both in vivo and ex vivo gene therapies. Conclusion: In this study, a lentiviral-mediated ex vivo and in vivo gene therapy was developed to provide a moderate dose of secukinumab in rat models. Biosimilar gene therapy is an attractive approach for the treatment of autoimmune disorders, cancers and other chronic diseases. [ABSTRACT FROM AUTHOR]