Journal of Genes and Cells

45-66

Authors: Monireh Bahrami

Cardiovascular problems have been known as largest cause of mortality in the world. It has been reported that only in U.S., 16.9 million deaths happen annually just because of coronary heart disease. Stem cells have shown a promising potential in regenerative medicine and more than 25,000 clinical trials have been completed so far. Stem cell researchers have ultimate aspiration to have successful cardiac regeneration and are working for the successful cardiac phenotype adaptation of transplanted stem cells. Obstacles and potential stem cell therapeutic risks associated with their clinical applications such as poor survival of the donor cells after engraftment etc, have reduced the translational potential of this research. In this review, we have focused on the advancement in cellular therapeutic efficacy for cardiac regeneration. It has been proposed that some engineering techniques applied to enhance therapeutic potential of stem cells have shown promising potential for daily routine clinical practice. Pre-clinical and clinical data have been presented to justify this improvement. The mechanisms to engineer cells for induction or alteration in stem cells for targeted therapy need recommendations for future clinical work to have a state-of-art approach in cardiac regeneration.

5-9

Authors: Habib Rezanejadbardeji ,Bahareh Behroozi-Asl, Raheleh Amirkhah

CRISPR/Cas system, a microbial adaptive immune system, has rapidly transformed the ways researchers can interrogate the genome. CRISPR has many advantages over traditional methods such as Transcription activator-like effector nucleases (TALEN) and Zinc-finger nucleases (ZFN). Since CRISPR discovery as an adaptive immune system used by bacterial against viruses, it has been repurposed to help in many different genome-related studies such as gene knocking in and out, gene expression upregulation and downregulation. Also CRISPR holds vast therapeutic potential for the management of genetic disorders by straight modifying disease-causing mutations. Although the Cas9 protein has been revealed to attach and cleave DNA at off-target sites, the field of Cas9 specificity is quickly progressing, with marked modifying in guide RNA choice, protein and guide engineering, innovative enzymes, and off-target recognition methods. In current review we mostly focus on CRISPR unique ability in gene activation/ upregulation, which has wide applications in different aspects such as gene studies, stem cell differentiation, and trans-differentiation. Compared to other gene activation methods such as viral gene overexpression, TALEN and ZFN, CRISPR offers many benefits such as easy designing and high precision.

33-39

Authors: Fahime Karimi, Mohammad Reza Hashemzadeh, Mohammad Amin Edalatmanesh ,Hojjat Naderi-Meshkin

Neural stem cells (NSCs) have considerable capacity for self-renewing and also ability for generating neurons in the mammalian brain. However, one of the big challenges is the migration and targeted homing of transplanted NSCs into the injured site to treat neurodegenerative diseases including Alzheimer´s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), brain ischemia (BI) and spinal cord injury (SCI). To improve homing capacity, pretreatment of NSCs with Valproic acid (VPA), which is supposed to cause diverse effects on migration ability of NSCs, is a strategy. More recently, hind brain and olfactory bulbs have been introduced as a good source of NSCs. So, NSCs were isolated from these two sources of postnatal day 1 (PND1) rats. These isolated cells were characterized by expressing neuronal markers such as Nestin and Sox2. The expression of four selected chemokine receptors (CXCR4, CXCR6, CCR1 and CCR7), which are important effectors in homing of stem cells, was investigated. It is concluded that VPA treatment enhances NSCs migration and homing showing its potential to be applied for cell-based therapies.

58-63

Authors: Afsaneh Farokhi ,Fatemeh Koohpeima, Mohammad Javad Mokhtari

Many studies have showed disadvantageous effect of ethanol exposure on stem cells. Ethanol exposure during development leads injury to various types of stem cells including neural stem cells (NSCs), dental pulp stem cells, mesenchymal stem cells, embryonic stem cells and etc. Because NSCs play a basic role in the development and maturation of the central nervous system, it is vital to understand the effect of ethanol on NSCs differentiation. Additionally, alcohol misusage appears lead to periodontal disease, tooth decay and mouth wounds that are potentially precancerous. Individuals who abuse alcohol are at high risk of having seriously destroyed teeth, gums and compromised oral health in general. Some of these adverse situations maybe are because of ethanol effects on stem cells. Therefore, here, ethanol effects on the various types of stem cells were reviewed.

69-75

Authors: Samira Malekzadeh, Mohammad Amin Edalatmanesh ,Davood Mehrabani, Mehrdad Shariati, Sima Malekzadeh

In recent years, stem cell therapy tried to improve the life of patients that suffer from neurodegenerative disease, like Alzheimer's disease. Although teeth are non-essential for life, but the dental tissues are an important source of mesenchymal stem cells that are suitable for neural regeneration. The studies showed that dental stem cells (DSCs) have the potential to differentiate into several cell types that among the most important is neural progenitor. In this review article, discusses the types of dental stem cells and then focused on application of dental stem cells on neural regeneration.

1-5

Authors: Samane Heidarzade, Seyed Mohammad Amin Kormi, Nasrin Malekpour, Shima Ardehkhani

Cancer progression and metastasis is rarely or less studied phenomenon. It has been known that cancer stem cells are the significant agents playing critical in metastasis and advanced tumorigenesis because of their heterogeneous nature. Their changed molecular expression with the passage of time and induction of normal cells into cancerous cells are correlated and determining these stem cell markers expression on CSCs can help to understand the progression of cancer and resistance to chemotherapy approaches. Identification of these signaling pathways and their modulation role are the key necessities for precise diagnosis and targeted therapeutic approaches development.

18-21

Authors: Jalal Omrani, Madjid Momeni-Moghaddam

Organ Bioprinting is a new approach in the field of regenerative medicine that try to make a whole intact functionally active organ from tissue specific cells. Providing such organs are very important because every year many patients need to organ transplantation but the number of donors are so limited. Organs made from different tissue with different kinds of cell types and for Organ Bioprinting first we need to provide these cell types. Currently, with regards to advances in stem cell biology specially invention of easy methods for isolation mesenchymal stem cells (MSCs) as one the appropriate cell type for regeneration purpose and also due to their unique properties including lack of immune-rejection in allograft, MSCs have gained attention for using in organ production. MSCs can isolate from many tissues of adults and differentiate in a targeted manner into cells of interest; provide a main material of tissue engineering triangle (i.e. cells, biomaterial and growth factors) for 3D bioprinting of human organs on a substrate. Printers have the ability of designing tissues and organs with fusing living tissue specific cells and extracellular matrix in layers to produce 3D biologically functional new organ. It is conceivable that in the near future, stem cells will play their predicted role; i.e. whole organ production.

39-46

Authors: Arash Akhavan Rezayat, Hamid Reza Rahimi, Atefe Joveini, Shahrzad Maraghe Moghadam, Ghasem Soltani, Mohammad Reza Khojasteh, Nahid Zirak

Objectives: Mesenchymal stem cells (MSCs) play an important role in treating damaged tissues, growing and developing body tissues. Nowadays, the injection of stem cells has been considered for therapeutic purposes. Some substances which can be effective in the success rate of treatment are injected with the stem cells in the stem cell therapy. Anesthetics are a group of them. Local anesthetics toxicity on tissues such as nerve, cartilage, muscle and tendon are well described in many studies. Studies show local anesthesia can be toxic for stem cells too, and induce MSCs apoptosis and necrosis As a result, repairing of tissue by stem cells can be in trouble in damaged tissue which exposure to LAs. According to this, it is important to find the appropriate LA which has the least toxic effect on stem cells. In this study, we have considered the effects of LA such as lidocaine, bupivacaine, ropivacaine and mepivacaine on MSCs. Literature review: Local anesthetics toxicity has been described on chondrocytes by several studies. In this study, we have tried to find the effects of these drugs on mesenchymal stem cells. We have arranged local anesthetics for toxic effects to MSCs from high to low. According to this arrangement bupivacaine is the first drug, after that there are mepivacaine, lidocaine and ropivacaine, respectively. This sequence can be true for increasing the cellular metabolism, adhesive cells adhesion and also cellular appendages. Conclusion: The studies have indicated that MSCs is more sensitive to local anesthetics in comparison with chondrocytes. In addition to type of LAs, exposure time and drug dose play an important role in damaging to the MSCs. In other word, LAs effects are dose-dependent and time-dependent. however, The studies consider lesser neurotoxicity and longer local anesthesia effect for bupivacaine in comparison with other LAs such as lidocaine but it is recommended to use drugs which are safer (such as ropivacaine) in procedures including stem cell therapy, prolonged anesthesia and tissues are repairing. Because bupivacaine has high toxicity effect on mesenchymal stem cells.