Public awareness and understanding of stem cell treatments available in Saudi Arabia and their trust in hospitals and research centers involved in stem cell research-a cross sectional study.

Introduction: Although stem cell research and therapeutic applications hold great promise for medical advancements, and have rapidly progressed globally, there remains a lack of genuine public awareness of the status of this subject in Saudi Arabia. Successful integration of stem cell therapy into healthcare relies on public awareness, understanding, and trust. Therefore, we aimed in this cross-sectional study to assess the public's knowledge, awareness, trust, support, participation, and confidence in stem cell treatments and centers involved in it. Materials and methods: A voluntary questionnaire of 20 questions was distributed randomly via social media outlets. Results: Three thousand five hundred eighty four individuals participated in the survey, with approximately half of them falling within the age range of 35-50 years (46.71%). Majority of the participants, 90.71%, would like to know more about stem cell therapy and more than half of the participants (56.94%) were unfamiliar with the idea, and a comparable proportion (50.41%) expressed concerns about the safety of stem cell therapy. A lower level of awareness, indicated by a score of 5, was evenly distributed across all age groups and genders. However, regardless of gender, older participants-especially those 50 years of age or older-tended to report higher levels of confidence, trust, and support than participants in other age groups. Moreover, trust, support, participation, and confidence score for those attained high school or less was statistically significantly lower than those attained master's or PhD degree. Of the participants, 33.57% had either received stem cell therapy themselves or known someone who had; about 24.07% of them reported that it was a cosmetic type of treatment. Conclusion: The study emphasizes the persistent need for awareness and educational initiatives to minimize the lack of public awareness and understanding of approved stem cell treatments in Saudi Arabia. It advocates for increased education, transparency, and communication to bridge knowledge gaps and enhance public trust to ensure the understanding of successful treatment.

Disease burden and projection of total and early-onset colorectal cancer in Gulf cooperation council countries from 1990 to 2019.

BACKGROUND: Early-onset colorectal cancer (EO-CRC) incidence and prevalence trends in the rise in high income countries, such as the Gulf Cooperation Council (GCC) countries. The study aimed to offer an up-to-date assessment of the overall burden of CRC, and EO-CRC in GCC countries and project its incidence and mortality in 2030. METHOD: The prevalence, incidence, mortality, years of life lived with disability (YLDs), and disability-adjusted life years (DALYs) of CRC were obtained from the Global Burden of Disease (GBD) Study 2019. The incidence and mortality of CRC, and EO-CRC up to 2030 were predicted. RESULTS: All GCC countries showed a higher annual average percentage changes (AAPC) AAPC incidence rate for EO-CRC compared to CRC. In Saudi Arabia the number of CRC cases has increased from 1990 1484.57; (95 % UI 1987.98,1083.86) 11.4-fold-increase to 16991.83; (95 % UI 21754.79,12892.12) in 2019. In 2030, the total incidence cases of CRC for the six Gulf countries are expected to reach 13,339 thousand, primarily driven by Saudi Arabia with 7,910.19 cases. In 2030, the CRC mortality rate is projected to be 7,647 cases, with nearly 57 % of CRC mortality cases anticipated in Saudi Arabia. CONCLUSION: This study sheds light on the alarming rise in CRC and EO-CRC across Gulf countries from 1990 to 2019, emphasizing Saudi Arabia's significant burden. It projects a concerning increase in CRC incidence and mortality by 2030, primarily in Saudi Arabia, and highlights the need for immediate public health interventions.

Generation of iPSC lines (KAIMRCi003A, KAIMRCi003B) from a Saudi patient with Dravet syndrome carrying homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A.

The most prevalent form of epileptic encephalopathy is Dravet syndrome (DRVT), which is triggered by the pathogenic variant SCN1A in 80% of cases. iPSCs with different SCN1A mutations have been constructed by several groups to model DRVT syndrome. However, no studies involving DRVT-iPSCs with rare genetic variants have been conducted. Here, we established two DRVT-iPSC lines harboring a homozygous mutation in the CPLX1 gene and heterozygous mutation in SCN9A gene. Therefore, the derivation of these iPSC lines provides a unique cellular platform to dissect the molecular mechanisms underlying the cellular dysfunctions consequent to CPLX1 and SCN9A mutations.

HLA-based banking of induced pluripotent stem cells in Saudi Arabia.

BACKGROUND: Human iPSCs' derivation and use in clinical studies are transforming medicine. Yet, there is a high cost and long waiting time associated with autologous iPS-based cellular therapy, and the genetic engineering of hypo-immunogenic iPS cell lines is hampered with numerous hurdles. Therefore, it is increasingly interesting to create cell stocks based on HLA haplotype distribution in a given population. This study aimed to assess the potential of HLA-based iPS banking for the Saudi population. METHODS: In this study, we interrogated the HLA database of the Saudi Stem Cell Donor Registry (SSCDR), containing high-resolution HLA genotype data from 64,315 registered Saudi donors at the time of analysis. This database was considered to be a representative sample of the Saudi population. The most frequent HLA haplotypes in the Saudi population were determined, and an in-house developed iterative algorithm was used to identify their HLA matching percentages in the SSCDR database and cumulative coverage. Subsequently, to develop a clinically relevant protocol for iPSCs generation, and to illustrate the applicability of the concept of HLA-based banking for cell therapy purposes, the first HLA-based iPS cell line in Saudi Arabia was generated. Clinically relevant methods were employed to generate the two iPS clones from a homozygous donor for the most prevalent HLA haplotype in the Saudi population. The generated lines were then assessed for pluripotency markers, and their ability to differentiate into all three germ layers, beating cardiomyocytes, and neural progenitors was examined. Additionally, the genetic stability of the HLA-iPS cell lines was verified by comparing the mutational burden in the clones and the original blood sample, using whole-genome sequencing. The standards set by the American College of Medical Genetics and Genomics (ACMG) were used to determine the clinical significance of identified variants. RESULTS: The analysis revealed that the establishment of only 13 iPSC lines would match 30% of the Saudi population, 39 lines would attain 50% coverage, and 596 lines would be necessary for over 90% coverage. The proof-of-concept HLA-iPSCs, which cover 6.1% of the Saudi population, successfully demonstrated pluripotency and the ability to differentiate into various cell types including beating cardiomyocytes and neuronal progenitors. The comprehensive genetic analysis corroborated that all identified variants in the derived iPSCs were inherently present in the original donor sample and were classified as benign according to the standards set by the ACMG. CONCLUSIONS: Our study sets a road map for introducing iPS-based cell therapy in the Kingdom of Saudi Arabia. It underscores the pragmatic approach of HLA-based iPSC banking which circumvents the limitations of autologous iPS-based cellular therapies. The successful generation and validation of iPSC lines based on the most prevalent HLA haplotype in the Saudi population signify a promising step toward broadening the accessibility and applicability of stem cell therapies and regenerative medicine in Saudi Arabia.

Mortality-to-incidence ratio of early-onset colorectal cancer in high-income Asian and Middle Eastern countries: A systemic analysis of the Global Burden of Diseases Study 2019.

BACKGROUND: The incidence of early-onset colorectal cancer (EO-CRC) has been consistently rising leading to a significant cancer burden among younger adults in Asian and Middle Eastern high-income countries. The study aims to investigate the survival outcomes of EO-CRC among high-income Asian and Middle Eastern populations from 1990 to 2019 using the mortality-to-incidence ratio, with a focus on examining the differences in gender. METHODS: This is a systematic analysis of the Global Burden of Disease (GBD) 2019 study. We include individuals aged 15 to 49 years old in high-income Asian and the Middle Eastern countries. The colorectal cancer mortality-to-incidence ratio (MIR) was calculated for both genders by dividing the age-specific mortality rate per 100,000 for colorectal cancer by the age-specific incidence rate per 100,000 for each nation in the sample for a given year. RESULTS: An overall decline in male and female MIR was observed from 1990 to 2019 in Asian and Middle Eastern countries. Ten out of thirteen Asian and Middle Eastern countries had a higher female MIR compared to their male counterparts. The global male MIR was found to be significantly higher than that of female (p-value 0.008, coefficient estimate: 1.51). In Middle Eastern countries, Saudi Arabia had a significantly higher female MIR compared to their male counterparts (p < 0.0001, coefficient estimate: 12.65). CONCLUSION: This research addresses the knowledge gap concerning gender-based differences in EO-CRC survival outcomes in high-income Asian and Middle Eastern countries, providing insights into the factors influencing these disparities in these regions. Policymakers should focus on developing targeted prevention and treatment programs for women, and addressing cultural and social barriers that may prevent women from seeking timely medical care.

Generation of myoglobin (MB)-knockout human embryonic stem cell (hESC) line (KAIMRCe002-A-1S) using CRISPR/Cas9 technology.

Myoglobin (MB) is a cytoplasmic hemoprotein that is predominantly expressed in the heart and oxidative myofibers of skeletal muscle. It has been demonstrated that MB binds to oxygen and promotes its diffusion for energy production in the mitochondria. Recently, MB was found to be expressed in different forms of malignant tumors and cancer cell lines. Further studies using gene disruption technology will enhance the understanding of MB's role in human cardiovascular biology and cancers. Here, we describe the generation of a homozygous MB knockout in human embryonic stem cells (hESC-MB-/-) via CRISPR/Cas9 to study MB function in human biology and diseases.

Early-Onset Colorectal Cancer Survival among Unscreened Population -Multicenter Cohort Retrospective Analysis.

BACKGROUND: In Saudi Arabia and across the world, the incidence of early-onset colorectal cancer (< 50 years) has increased. The diagnosis of EOCRC, on the other hand, is frequently delayed. It is critical to implement a national screening program to identify those group of patients who might benefit from early diagnosis. METHOD: A retrospective search was conducted using data from the Ministry of National Guard Health Affairs' (MNG-HA) Cancer Registry. The population of 1440 CRC patients were eligible for the analyses. Patients' demographics including age at diagnosis, gender, and marital status, were all reported. The demographic and clinical characteristics were assessed across early-onset and late-onset groups using Chi-square and Fisher exact test where appropriate. RESULTS: CRC patients, early-onset CRC (18-50 years) was reported in 23.26%, mainly with advance disease. Late-onset (>50 years) CRC individuals have worse survival rate and higher probability of dying compared to early-onset CRC individuals. After age at diagnosis classification into three categories (18-40 years), (41-50 years), and (>50 years) the Kaplan-Meier Survival curve show that early-onset (18-40 years) CRC individuals had significantly better survival than (41-50 years), and (>50 years) CRC patients. CONCLUSIONS: Comparing our data to another screened population using US SEER datasets, we discovered a substantial difference in survival rates, with the SEER population having a considerably greater chance of survival. There is very little research on the significance of screening for Saudi CRC patients, and this is an issue that needs to be looked into more. LIMITATIONS: A study's drawback is the lack of data for a variety of risk variables linked to colorectal cancer incidence, such as the KRAS mutation and environmental risk factors including BMI and smoking. More research with a nationally representative sample and comprehensive demographic and clinical data accessible is needed.

The emerging role of MCPH1/BRIT1 in carcinogenesis.

The MCPH1 gene, also known as BRCT-repeat inhibitor of hTERT expression (BRIT1), has three BRCA1 carboxyl-terminal domains which is an important regulator of DNA repair, cell cycle checkpoints and chromosome condensation. MCPH1/BRIT1 is also known as a tumour suppressor in different types of human cancer. The expression level of the MCPH1/BRIT1 gene is decreased at the DNA, RNA or protein level in a number of types of cancers including breast cancer, lung cancer, cervical cancer, prostate cancer and ovarian cancer compared to normal tissue. This review also showed that deregulation of MCPH1/BRIT1 is significantly associated with reduced overall survival in 57% (12/21) and relapsed free survival in 33% (7/21) of cancer types especially in oesophageal squamous cell carcinoma and renal clear cell carcinoma. A common finding of this study is that the loss of MCPH1/BRIT1 gene expression plays a key role in promoting genome instability and mutations supporting its function as a tumour suppressor gene.

An Update on Alopecia and its Association With Thyroid Autoimmune Diseases.

Alopecia is comorbid with several illnesses, including various autoimmune conditions such as thyroid disease. Leukocyte-mediated inflammation of hair follicles in alopecia was first described over a century ago. However, the high prevalence of the role of thyroid autoimmune disease in the pathogenesis of alopecia has only recently come to light, together with a strong association between the two. Therefore, this review focuses on articles published between 2011 and 2022 on alopecia's association with thyroid autoimmune disease, and the mechanism behind it. In addition, it highlights the link between alopecia and thyroid cancer, as patients with alopecia have increased risk of thyroid cancer. In conclusion, this comprehensive, focused, scoping review will serve as a reference highlighting recent information on alopecia, exploring its association with thyroid autoimmune diseases.

An Infodemic of Misinformation on Stem Cell Therapy Among the Population of Saudi Arabia: A Cross-Sectional Study.

In recent years, the industry of unproven stem cell-based therapies has been on the rise around the globe, putting patients at great risk of potential harm. In this cross-sectional study, we aimed to assess the level of knowledge and awareness of the general public, including patients and/or their relatives, in Saudi Arabia on stem cell therapy and to assess the degree of willingness to try stem cell-based treatment options, should it be offered to them. Methods: A voluntary questionnaire of 16 questions was distributed randomly through social media outlets. Results: In the survey of this study, 2,030 individuals participated. A total of 1,292 (63.6%) stated that they would accept stem cell therapy or would recommend it to their friends and relatives. Alarmingly, 72.1% of participants were unaware that using unapproved stem cell-based treatments may lead to serious health complications including cancer. More than 20% believed that stem cell therapy is already approved for organ/tissue regeneration. Worryingly, 60.6% of the physicians and 56.4% of the medical students stated that they would recommend stem cell treatment for their patients. Conclusions: There is a concerning spread of misinformation among the Saudi population, including physicians, regarding stem cell therapy. This calls for a targeted effort to raise awareness about the current status of stem cell treatment in the general public and among health care practitioners.

Generation of induced pluripotent stem cell Line KAIMRCi001-A by reprogramming erythroid progenitors from peripheral blood of a healthy Saudi donor.

In this study we isolated and enriched erythroid progenitor cells (EPCs) from a 10 ml peripheral blood sample from a 37-year old healthy Saudi donor. After expansion, these EPCs were reprogrammed using episomal plasmids to generate an induced pluripotent stem (iPS) cell line, KAIMRCi001-A. The pluripotency of this line was confirmed by measuring the expression of typical pluripotency markers and assessing differentiation potential in vitro.

Insulin-Like Growth Factor Binding Protein-6 Promotes the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle Independent of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor.

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.

Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle Differentiation of Human Mesenchymal Stem Cells.

Insulin-like growth factor binding protein-6 (IGFBP-6), the main regulator of insulin-like growth factor-2 (IGF-2), is a component of the stem cell niche in developing muscle cells. However, its role in muscle development has not been clearly defined. In this study, we investigated the role of IGFBP-6 in muscle commitment and differentiation of human mesenchymal stem cells derived from the placenta. We showed that placental mesenchymal stem cells (PMSCs) have the ability to differentiate into muscle cells when exposed to a specific culture medium by expressing muscle markers Pax3/7, MyoD, myogenin, and myosin heavy chain in a stage-dependent manner with the ultimate formation of multinucleated fibers and losing pluripotency-associated markers, OCT4 and SOX2. The addition of IGFBP-6 significantly increased pluripotency-associated markers as well as muscle differentiation markers at earlier time points, but the latter decreased with time. On the other hand, silencing IGFBP-6 decreased both pluripotent and differentiation markers at early time points. The levels of these markers increased as IGFBP-6 levels were restored. These findings indicate that IGFBP-6 influences MSC pluripotency and myogenic differentiation, with more prominent effects observed at the beginning of the differentiation process before muscle commitment.

The Roles of Insulin-Like Growth Factors in Mesenchymal Stem Cell Niche.

Many tissues contain adult mesenchymal stem cells (MSCs), which may be used in tissue regeneration therapies. However, the MSC availability in most tissues is limited which demands expansion in vitro following isolation. Like many developing cells, the state of MSCs is affected by the surrounding microenvironment, and mimicking this natural microenvironment that supports multipotent or differentiated state in vivo is essential to understand for the successful use of MSC in regenerative therapies. Many researchers are, therefore, optimizing cell culture conditions in vitro by altering growth factors, extracellular matrices, chemicals, oxygen tension, and surrounding pH to enhance stem cells self-renewal or differentiation. Insulin-like growth factors (IGFs) system has been demonstrated to play an important role in stem cell biology to either promote proliferation and self-renewal or enhance differentiation onset and outcome, depending on the cell culture conditions. In this review, we will describe the importance of IGFs, IGF-1 and IGF-2, in development and in the MSC niche and how they affect the pluripotency or differentiation towards multiple lineages of the three germ layers.

Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells.

Insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6), which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs) into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.