Regenerative application of oral and maxillofacial 3D organoids based on dental pulp stem cell.

Dental pulp stem cells (DPSCs) originate from the neural crest and the present mesenchymal phenotype showed self-renewal capabilities and can differentiate into at least three lineages. DPSCs are easily isolated with minimal harm, no notable ethical constraints, and without general anesthesia to the donor individuals. Furthermore, cryopreservation of DPSCs provides this opportunity for autologous transplantation in future studies without fundamental changes in stemness, viability, proliferation, and differentiating features. Current approaches for pulp tissue regeneration include pulp revascularization, cell-homing-based regenerative endodontic treatment (RET), cell-transplantation-based regenerative endodontic treatment, and allogeneic transplantation. In recent years, a novel technology, organoid, provides a mimic physiological condition and tissue construct that can be applied for tissue engineering, genetic manipulation, disease modeling, single-cell high throughput analysis, living biobank, cryopreserving and maintaining cells, and therapeutic approaches based on personalized medicine. The organoids can be a reliable preclinical prediction model for evaluating cell behavior, monitoring drug response or resistance, and comparing healthy and pathological conditions for therapeutic and prognostic approaches. In the current review, we focused on the promising application of 3D organoid technology based on DPSCs in oral and maxillofacial tissue regeneration. We discussed encountering challenges and limitations, and found promising solutions to overcome obstacles.

Association between Vitamin D Receptor Polymorphism and Susceptibility to Oral Lichen Planus and Oral Squamous Cell Carcinoma.

Introduction: Oral squamous cell carcinomas (OSCC) comprise 90-95% of oral cancers. Early diagnosis improved the survival rate of OSCC patients to 80-90%. Oral lichen planus (OLP) is a chorionic inflammatory disease with malignancy potential. The vitamin D receptor (VDR) plays a critical role in the pathogenesis of oral cancer. This study aimed to determine the association between VDR rs7975232 (Apa I) polymorphism and potential susceptibility to OLP and OSCC risks. Materials and Methods: In this prospective case-control study, a total of 120 blood samples were obtained from OSCC patients (n=29), OLP (n=50), and controls (n=40). VDR rs7975232 polymorphism was studied using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) method. Statistical analysis was performed with SPSS Version 23 software. Data were expressed as means ± standard deviation (SD). Age, sex, allelic frequency, and genotyping were compared using the chi-square test. A p-value of less than 0.05 was regarded as statistically significant. The disease risk was estimated by Odds ratio (OR) with a 95% confidence interval. Results: A significant age difference was observed between the controls and the OSCC group (p=0.001). A significant difference was observed in Aa and aa genotypes compared with AA between OSCCs and controls. Moreover, dominant (p<0.001), additive (p<0.001), and allelic (p=0.001) models were different between groups. Conclusion: There was a positive association between rs7975232 VDR polymorphism and susceptibility to OSCC. More experimental evidence must reveal the possible association between rs7975232 and the risk of OLP in a larger cohort.

Downregulation of salivary miR-3928 as a potential biomarker in patients with oral squamous cell carcinoma and oral lichen planus.

OBJECTIVES: Recent studies highlighted the role of miR expressed in saliva as reliable diagnostic and prognostic tools in the long-term monitoring of cancer processes such as oral squamous carcinoma (OSCC). Based on a few previous studies, it seems the miR-3928 can be considered a master regulator in carcinogenesis, and it can be therapeutically exploited. This is the first study that compared oral potentially malignant disorder (OLP) and malignant (OSCC) lesions for miR-3928 expression. MATERIALS AND METHODS: In this cross-sectional study, saliva samples from 30 healthy control individuals, 30 patients with erosive/atrophic oral lichen planus, and 31 patients with OSCC were collected. The evaluation of miR-3928 expression by q-PCR and its correlation with clinicopathological indices were analyzed by Shapiro-Wilk, Kruskal-Wallis, Pearson's χ2 , and Mann-Whitney tests. The p-value less than .05 indicated statistically significant results. RESULTS: Based on nonparametric Kruskal-Wallis test results, there was a statistically significant difference between the ages of three study groups (p < .05). This test demonstrated a statistically significant difference between the average of miR-3928 expression in three study groups (p < .05). The result of the χ2  test showed a statistically significant difference in miR-3928 expression between patients with OLP (p = .01) and also patients with OSCC (p < .0001) in comparison to the control group. CONCLUSIONS: The salivary miR-3928 can play a tumor suppressive role in the pathobiology of OSCC, and it is significantly downregulated in patients. According to the potential tumor suppressive role of miR-3928 in the OSCC process, we can consider this microRNA as a biomarker for future early diagnosis, screening, and potential target therapy.

Clinical value and potential circulating of miR-99a as tumor suppressor biomarker in serum of oral squamous cell carcinoma and erosive atrophic lichen planus.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common type of oral neoplasms that consist of more over 90% of oral cancers. It was demonstrated that erosive atrophic oral lichen planus (OLP) has potential of malignancy transformation into OSCC. The microRNAs are non-coding regulator sequences involved in cancer process. The miR-99a involve in growth, proliferation, migration, invasion, and metastasis of tumor cells. Therefore, we evaluated miR-99a expression in serum of OSCC and erosive atrophic OLP patients in comparison to healthy control individuals to more investigate about level of miR-99a expression in potential premalignant disorder (erosive atrophic OLP) in comparison to malignant transformation form (OSCC). Gene ontology (GO) and pathway analyses were performed to better understand the importance of miR-99a in OSCC. MATERIALS AND METHODS: In this cross-sectional study, total 90 serum samples from OSCC patients (n = 30), erosive atrophic OLP (n = 30) and healthy control individuals (n = 30) were collected, and then evaluated for miR-99a expression by qPCR. Pathway analysis and protein-protein interaction were done using STRING (v: 12.0), and (GO) terms and related genes were extracted from the GO online search tool. The statistical analysis was evaluated by Kruskal Wallis, Chi-Square, Kruskal Wallis, Spearman and Mann-Whitney tests. The p-value less than 0.05 was considered statistically significant. RESULTS: miR-99a expression down regulated in OSCC in comparison to erosive atrophic OLP and control groups (p < 0.05). The miR-99a up regulated in grade I more than grades II and III (p < 0.05). We showed upregulation of miR-99a in early stage more than advanced stage (p < 0.05). Expression of miR-99a reduced accordance to the increasing of tumor size and lymph involvement levels (p < 0.05). The 165 determined targets were classified into three domains. The most significant enrichment in biological processes, cellular components, and molecular functions was in the cellular nitrogen compound biosynthetic process, cytosolic ribosome, and protein binding, respectively. CONCLUSIONS: We highlighted tumor suppressive role of miR-99a in OSCC patients. It seems that miR-99a can be considered a valuable biomarker for the early diagnosis of erosive atrophic OLP before transformation. CLINICAL RELEVANCE: Our results may help to better understand the prognostic factor for oral squamous cell carcinoma to evaluate survival and subsequent tumor development. And it may also help to understand the pathogenesis of OSCC.

Salivary Antiviral and Antibacterial Properties in the Encounter of SARS-CoV-2.

Due to the high mortality rate of COVID-19 and its high variability and mutability, it is essential to know the body's defense mechanisms against this virus. Saliva has numerous functions, such as digestion, protection, and antimicrobial effects. Salivary diagnostic tests for many oral and systemic diseases will be available soon because saliva is a pool of biological markers. The most important antiviral and antibacterial compounds identified in saliva include lysozyme, lactoferrin (LF), mucins, cathelicidin, salivary secretory immunoglobulin (SIgA), chromogranin A, cathelicidin, salivary agglutinin (SAG) (gp340, DMBT1), α, ß defensins, cystatin, histatins, secretory leukocyte protease inhibitor (SLPI), heat shock protein (HSP), adrenomedullin and microRNA (miRNAs). Antimicrobial peptides (AMPs) in saliva could be used in the future as models for designing effective oral microbial antibiotics. The antiviral properties of the peptides in saliva may be one of the future treatments for the COVID-19 virus. In this review, we investigate compounds with antiviral and antibacterial properties in saliva and the importance of these compounds in saliva in exposure to the COVID-19 virus. Due to the transmission route of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) into the oral cavity in the lower and upper respiratory tract, studies of salivary antiviral properties in these patients are very important. Some of the antiviral effects of saliva, especially mucin, α, ß-defensins, IgA, IgG, IgM, lysozyme, SAG, SLPI, and histatins, may play a greater role in neutralizing or eliminating COVID-19.

Associations between RORγt and T-bet Expressions, clinicopathological indices and survival rate in oral Squamous cell carcinoma patients.

BACKGROUND: Oral cancers are the sixth most common cancers around the world. According to the pivotal role of immune cells in the pathogenesis of oral squamous cell carcinoma (OSCC), as the frequent form of malignant epithelial neoplasm in the oral cavity, we investigated the association between the expression of RORγt and T-bet genes as two transcription factors, clinicopathologic indices, and survival rate. METHODS AND MATERIALS: Forty-two OSCC paraffin embded-blocks tissue samples and their surgical healthy margins (as a control group) were collected. Demographic information like age and gender, and medical history including tumor stage/grade, and following-up time were registered. The RORγt and T-bet expression were assessed by qPCR. The overall survival (OS) and disease free survival (DFS) were analyzed by SPSS V.23 software. RESULTS: The expression of RORγt and T-bet genes in OSCC patients were significantly higher than in surgical healthy margins (P < 0.001). Both expression demonstrated a significant difference between surgical healthy margins and tumor tissues related to gender and clinicopathological indices including stage and grade (P < 0.05). The expression of both genes in stage I patients was significant compared to stage IV (P < 0.05). The relation between expressions, OS, and DFS with clinical stage and histological grade of tumors was not statistically significant (P > 0.05). CONCLUSION: Overexpression of RORγt and T-bet in OSCC patients with higher grade and stage in compare to surgical healthy margin highlighted their critical role in OSCC pathogenesis including oral epithelial cell differentiation, tumorigenesis process, and malignant transformation. Moreover, both mentioned genes can apply as prognostic biomarkers in OSCC patients. We suggest surgical healthy margin be considered as valuable biological area.

The organoid as reliable cancer modeling in personalized medicine, does applicable in precision medicine of head and neck squamous cell carcinoma?

Head and neck squamous cell carcinomas (HNSCCs) are introduced as the sixth most common cancer in the world. Detection of predictive biomarkers improve early diagnosis and prognosis. Recent cancer researches provide a new avenue for organoids, known as "mini-organs" in a dish, such as patient-derived organoids (PDOs), for cancer modeling. HNSCC burden, heterogeneity, mutations, and organoid give opportunities for the evaluation of drug sensitivity/resistance response according to the unique genetic profile signature. The Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) nucleases, as an efficient genome engineering technology, can be used for genetic manipulation in three-dimensional (3D) organoids for cancer modeling by targeting oncogenes/tumor suppressor genes. Moreover, single-cell analysis of circulating tumor cells (CTCs) improved understanding of molecular angiogenesis, distance metastasis, and drug screening without the need for tissue biopsy. Organoids allow us to investigate the biopathogenesis of cancer, tumor cell behavior, and drug screening in a living biobank according to the specific genetic profile of patients.

The role of altered microRNA expression in premalignant and malignant head and neck lesions with epithelial origin.

Background and Aims: The premalignant lesions of the oral cavity carry a risk of transformation to malignancy. Hence, early diagnosis followed by timely intervention remarkably affects the prognosis of patients. During tumorigenesis, particular microRNAs (miRNAs) show altered expressions and because of their post transcriptionally regulatory role could provide favorable diagnostic, therapeutic, or prognostic values in head and neck cancers. Methods: In this review, we have demonstrated diagnostic, prognostic, and potential therapeutic roles of some miRNAs associated with oral premalignant and malignant lesions based on previous validate studies. Results: It is previously documented that dysregulation of miRNAs contributes to cancer development and progression. MiRNAs could be tumor suppressors that normally suppress cell proliferation, differentiation, and apoptosis or play as oncogenes that improved tumorigenesis process. Altered expression of miRNAs has also been reported in premalignant oral epithelial lesions such as leukoplakia, oral submucous fibrosis, oral lichen planus and some malignant carcinoma like oral squamous cell, verrucous, spindle cell, Merkel cell carcinoma and basal cell. Conclusion: Some of miRNAs could be new therapeutic candidates in miRNA-based target gene therapy. Although more investigations are required to identify the most favorable miRNA candidate, altered expression of some miRNAs could be used as biomarkers in premalignant lesions and oral cancers with high sensitivity and specificity.

Evaluation of CD4+ tumor-infiltrating lymphocyte association with some clinicopathological indices of oral squamous cell carcinoma.

Background: The delayed diagnosis of oral squamous cell carcinoma (OSCC) affects therapeutic and prognostic strategies, and provides regional recurrence or distant metastasis. The tumor-infiltrating lymphocytes (TILs) are known as a critical diagnostic biomarker in antitumor immune response. We evaluated the association between CD4+ T-lymphocyte marker, some clinicopathological indices, and the impact of TILs on the stage and grade of OSCC. Materials and Methods: In this cross-sectional study, 37 OSCC specimens including 16 early and 21 advanced stages (categorized base-on recent clinical oncology references) and their related healthy surgical margin (as internal control group) were collected. Obtained histochemical data were analyzed by SPSS V.23 software. The expression of CD4+ marker in tumor microenvironment (TME) was compared by nonparametric Mann-Whitney and Kruskal-Wallis as well as Fisher's exact tests. P < 0.05 was remarked statistically significant. Results: The low-grade patients represented more CD4+ TIL that was statistically significant (P = 0.011). However, there was no statistically significant difference in CD4+ TIL between various stages (P = 0.404), tumor size, and lymph node involvement (P > 0.05). Moreover, there was no significant relation between TIL infiltration, age, and tumor localization (P > 0.05), however CD4+ expression in women was more than men (P = 0.008). The CD4+ T-lymphocyte infiltration in TME was more significant than healthy surgical margin (P < 0.001). There was a statistically significant difference between healthy surgical margin and different grades and stages of OSCCs that lower grades demonstrated more CD4+ TIL infiltration (P < 0.001). Conclusion: The CD4+ T-lymphocytes may play important role in differentiation and maturity of epithelial cell, tumorigenesis, and progression of OSCC.

Association between Tissue Expression of Toll-Like Receptor and Some Clinicopathological Indices in Oral Squamous Cell Carcinoma.

Background: The oral squamous cell carcinoma (OSCC) composes about 90% of all head and neck cancers. The toll-like receptor (TLR)+ immune cells have potential of invasion and malignancy transformation. The aim of this study was assessment of possible associations between clinicopathological indices and TLR2 and TLR9 gene expression in OSCC. Methods: Forty-two OSCC samples with related healthy margins including 25 early and 17 advanced stages were gathered. The samples were classified histologically from grade I to II. The expression of TLR2 and TLR2 was evaluated by Real-time PCR. The patient's disease-free survival (DFS) and overall survival (OS) were analyzed using SPSS V.23 software. Results: The expression of TLR2 and TLR9 genes in tumor tissues (especially in grade I and II) were higher than healthy surgical margin tissue (p< 0.001). TLR9 expression in grade II was statistically significant than grade I in tumor tissue (p< 0.001). TLR9 expression in advanced stage was statistically significant in compare to early stage (p= 0.012). In advanced stage both overall survival (p= 0.029) and disease-free survival (p= 0.012) were statistically lower than early stage. The follow-up time to recurrence in advanced stage was statistically lower than early stage (p= 0.007). Conclusion: Overexpression of TLRs 2, 9 play role in the pathogenesis and tumor development of OSCC and can be applied as biomarker in prognostic approaches.

Inhibition of angiotensin pathway via valsartan reduces tumor growth in models of colorectal cancer.

BACKGROUND: Overexpression of the angiotensin-II receptor and renin-angiotensin system (RAS) has been reported in several malignancies, including colorectal-cancer (CRC), indicating its potential value as a therapeutic target. Here we explored the impact of targeting the RAS using an angiotensin II receptor blocker, valsartan, alone and its combination with Fluorouracil (5-FU) in in vitro and in vivo models of CRC. METHODS: Anti-proliferative activity of valsartan was evaluated in 2-/3-dimensional in vitro and in vivo CRC mouse models. The anti-migratory effects of this agent was assessed by wound-healing assay, while apoptosis was studied using 4',6-diamidino-2-phenylindole or DAPI staining, and staining with Annexin-V-fluorescein isothiocyanate with analysis using FACS. Gene-expression was determined at mRNA and protein levels. We further evaluated the anti-inflammatory properties of valsartan by histological analysis and the measurement of oxidative/antioxidant markers. Gelatin zymography was used to measure matrix metalloproteinase-2 and -9 activity (MMP-2 and 9). RESULTS: Valsartan suppressed CRC cell-growth and synergistically enhanced the anti-tumor-activities of 5-FU by induction of apoptosis, BAX, BCL2, P53 and modulation of the cell cycle. Valsartan inhibited the cell migration by perturbation of MMP2/9. Furthermore, valsartan inhibited tumor-growth, and this was more pronounced when using the valsartan/5-FU combination. The plausible mechanism for this is via the induction of ROS and down-regulation of SOD, thiol/catalase as well as VEGF. Valsartan may protect cells against intestinal fibrosis by modulation of pro-fibrotic and pro-inflammatory factors including interleukins and Col1A1 expression. CONCLUSIONS: Our findings demonstrated that targeting RAS pathway using Valsartan interferes with cell-proliferation, induces apoptosis, reduces migration and synergistically interacts with 5-FU, supporting further studies on this new therapeutic approach for colorectal cancer.

New diagnostic molecular markers and biomarkers in odontogenic tumors.

Odontogenic tumors comprised of complex heterogeneous lesions that diverse from harmatomas to malignant tumors with different behavior and histology. The etiology of odontogenic tumors is not exactly determined and pathologists deal with challenges in diagnosis of odontogenic tumors because they are rare and obtained experiences are difficult to evaluate. In this study, we describe immunohistochemical and molecular markers in diagnosis of odontogenic tumors besides advanced diagnostic technique. Immunohistochemical features of odontogenic tumors beside the clinical features and radiological finding can help us to determine the correct diagnosis. Although these markers are neither specific nor sensitive enough, but analysis of gene expression provides definitive confirmation of diagnosis. In addition, "-omics" technology detected specific molecular alternation associated with etiology such as genomics, epigenomics, transcriptomics, proteomics and metabolomics. The post transcriptional events such as DNA methylation and chromatin remodeling by histone modification affect the changes in epigenome. Furthermore, non-coding RNAs like micro-RNAs, long noncoding RNA (lncRNA) and small non-coding RNA (snoRNA) play regulatory role and impact odontogenesis. Molecular marker propose their potential role in etiopathogenesis of odontogenic tumors and suitable candidate in diagnostic, prognostic and therapeutic approaches in addition to patient management. For future evaluations, organoid represents in vitro tumor model-study for tumor behavior, metastasis and invasion, drug screening, immunotherapy, clinical trial, hallmarks association with prognosis and evolution of personalized anti-cancer therapy. Moreover, organoid biobank help us to check genetic profile. We think more investigation and studies are needed to gain these knowledges that can shift therapeutic approaches to target therapy.

Potential therapeutic approaches of microRNAs for COVID-19: Challenges and opportunities.

The coronavirus disease 2019 (COVID-19) emerges as current outbreak cause by Novel Severe Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2). This infection affects respiratory system and provides uncontrolled systemic inflammatory response as cytokine storm. The main concern about SARS-CoV-2 pandemic is high viral pathogenicity with no specific drugs. MicroRNAs (miRs) as small non-coding RNAs (21-25 â€‹nt) regulate gene expression. The SARS-CoV-2 encoded-miRs affect human genes that involved in transcription, translation, apoptosis, immune response and inflammation. Also, they alter self-gene regulation and hijacked host miRs that provide protective environment to maintain its latency. On the other hand, Host miRs play critical role in viral gene expression to restrict infection. Over expression/inhibition of miRs might result in cell cycle irregularity, impaired immune response or cancer. In this manner, exact role of each miR should be specified. Mimic encoded-miRs like antagomirs showed successful result in phases of clinical trial prevent from negative effects of viral encoded-miRs. Products of mimic miRs are inexpensive corresponds to synthesis of primer; they are short and nanoscale in size. Although SARS-CoV-2 genome is undergoing evaluation, detection of exact molecular pathogenesis open up opportunities to for vaccine development. Salivaomics can evaluate SARS-CoV-2 genome, transcriptome, proteome and biomarkers like miRs in oral related and cancer disease. In this review, we studied the challenge and opportunities of miRs in therapeutic approach for SARS-CoV-2 infection, then overviewed the role of miRs in saliva droplet during SARS-CoV-2 infection and related cancer.

Effects of moderate exercise on lipopolysaccharide-induced inflammatory responses in rat's cardiac tissue.

The effects of moderate exercise on cardiac tissue inflammation, oxidative stress markers and apoptosis in lipopolysaccharide (LPS)-administered rats were evaluated. Wistar rats were divided into three groups (N = 8): (1) control; (2) LPS (1 mg/kg); and (3) LPS + moderate training (LPS + EX: 15 m/min, 30 min/day, for 9 weeks (week 1-9)). LPS was injected intraperitoneally for 5 days during week 9. Finally, the rats' heart were removed for biochemical and expression assessments. LPS increased the levels of tumor necrosis factor α (TNF-α), interleukin (IL)- 1ß, C-reactive protein (CRP), malondialdehyde (MDA) and nitric oxide (NO) metabolites in cardiac tissue, but decreased thiol contents and catalase (CAT) and superoxide dismutase (SOD) activity in cardiac tissue compared to the control group (p < 0.05-p < 0.001). In LPS + EX group, the level of NO metabolites was increased (p < 0.05) and thiol contents were decreased (p < 0.001) compared to the control group. Moderate training decreased the levels of TNF-α, IL-1ß, CRP and NO metabolites while increased CAT activity in the LPS + EX group compared to the LPS group (p < 0.05-p < 0.001). The mRNA level of BAX in the LPS group and the BCL2/BAX ratio in both LPS and LPS + EX groups increased compared to the control group (p < 0.05-p < 0.01). These results indicated that moderate training improved LPS-induced deleterious effects on cardiac tissue by attenuating proinflammatory cytokine levels, apoptosis and oxidative damage.

The effect of environmental lead exposure on human health and the contribution of inflammatory mechanisms, a review.

Lead (Pb) pollution has been considered as a major threat for human health due to induction of inflammatory cascades in various tissues. The aim of present review is to summarize the literature on the effects of lead exposure on respiratory, neurologic, digestive, cardiovascular and urinary disorders and the role of inflammation as an underlying mechanism for these effects. Various databases such as ISI Web of Knowledge, Medline, PubMed, Scopus, Google Scholar and Iran Medex, were searched from 1970 to November 2017 to gather the required articles using appropriate keywords such as lead, respiratory disorders, neurologic disorders, digestive disorders, cardiovascular disorders, urinary disorders and inflammation. Disorders of various body systems and the role of inflammation due to lead exposure has been proven by various studies. These studies indicate that lead exposure may cause respiratory, neurologic, digestive, cardiovascular and urinary diseases. The results were also indicated the increased inflammatory cells and mediators due to lead exposure including cytokines and chemokines due to lead exposure which suggested to be the cause various organ disorders.

The molecular signature of breast cancer metastasis to bone.

Distant metastasis during the advanced stage of malignant tumor progression can cause considerable morbidity in cancer patients. Bone is known to be one of the most common sites of distant metastasis in patients with breast cancer (BC). BC metastases in bone are associated with excessive skeletal complications. These complications can be fatal and reduce quality of life of patients. It is important to understand the metastatic process of BC to bone to improve quality of life and design new therapeutic methods. At present, the molecular mechanisms leading to the BC metastasis to bone are not fully understood. Studying the molecular basis of BC metastasis to bone might improve our insight into this complex process. In addition, it can provide novel approaches for designing advanced and effective targeted therapies. The present article aimed to review the published papers on the molecular basis of the metastatic process of BC to bone, focusing on involved genes and signaling networks. Furthermore, we propose potential therapeutic targets that may be more effective for the inhibition and treatment of BC metastasis to bone.

Autologous Hematopoietic Stem Cells transplantation and genetic modification of CCR5 m303/m303 mutant patient for HIV/AIDS.

HIV and AIDS is one of the biggest challenges all over the world. There are an approximately 34 million people living with the virus, and a large number of them become infected each year. Although there are some antiviral drugs for HIV viral load reduction, they are not sufficient. There is no cure for AIDS. Nowadays natural resistance or immunity has absorbed attentions. Because in some HIV positive patients progression trend is slow or even they indicate resistance to AIDS. One of the most interesting approaches in this category is CCR5 gene. CCR5 is a main cc-chemokine co-receptor that facilitates HIV-1 entry to macrophage and CD4(+) T cells. To now, many polymorphisms have been known by CCR5 gene that produces a truncated protein with no function. So, HIV-1 could not entry to immune-cells and the body resistant to HIV/AIDS. Δ32/Δ32 and m303/m303 homozygotes are example of mutations that could create this resistance mechanism. There is a new treatment, such as Hematopoietic Stem Cell transplantation (HSCT) in Berlin and Boston patients for Δ32/Δ32 mutation. It could eliminate co-receptor antagonist and highly-active-anti retroviral therapy (HAART) drugs problems such as toxicity, low safety and side-effects. Now there, the aim of this hypothesis will be evaluation of a new mutation CCR5 m303/m303 as autologous HSCT. This novel hypothesis indicates that autologous HSCT for m303/m303 could be effective treatment for anyone HIV/AIDS affected patient worldwide.