Cell and Developmental Biology Commons^™

A Probabilistic Approach To Estimate The Temporal Order Of Pathway Mutations Accounting For Intra-Tumor Heterogeneity, Menghan Wang, Yanqi Xie, Jinpeng Liu, Austin Li, Li Chen, Arnold Stromberg, Susanne Arnold, Chunming Liu, Chi Wang

Markey Cancer Center Faculty Publications

The development of cancer involves the accumulation of somatic mutations in several essential biological pathways. Delineating the temporal order of pathway mutations during tumori- genesis is crucial for comprehending the biological mechanisms underlying cancer development and identifying potential targets for therapeutic intervention. Several computational and statistical methods have been introduced for estimating the order of somatic mutations based on mutation profile data from a cohort of patients. However, one major issue of current methods is that they do not take into account intra-tumor heterogeneity (ITH), which limits their ability to accurately discern the order of pathway mutations. To address this …

T. Boudieri Extract Potentiates The Effects Of Capecitabine Treatment In Human Colon Cancer Cells, Katia Sawaya, Mahmoud Khalil, Ghada Khawaja

BAU Journal - Science and Technology

Resistance to chemotherapy remains a major challenge for colorectal cancer patients worldwide, hence the persistent need to uncover alternative treatments as well as new adjunct therapies in the fight against cancer. Natural extracts constitute an excellent source of bioactive substances that have a promising potential in that regard, with minimal negative side effects. We have previously demonstrated that both the ethanolic as well as the water extracts of Terfezia boudieri, a black desert truffle abundant in and part of the cuisine of the Mediterranean region, have significant antiproliferative effects against colon cancer cells. Our aim in this study was …

Altered Extracellular Matrix Correlates With An Immunosuppressive Tumor Microenvironment And Disease Progression In Younger Adults With Oral Cavity Squamous Cell Carcinoma, Leonard Estephan, Gaurav Kumar, Matthew Stewart, Raphael Banoub, Alban Linnenbach, Larry Harshyne, Ubaldo Martinez-Outshoorn, My Mahoney, Joseph Curry, Jennifer Johnson, Andrew South, Adam Luginbuhl

Kimmel Cancer Center Faculty Papers

INTRODUCTION: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options.

METHODS: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults …

Neuroinflammation In Alzheimer’S Disease Mouse Brain Following Repetitive Mild Traumatic Brain Injury, Lujain Almuhanna

Electronic Theses and Dissertations

Traumatic brain injuries (TBIs) are a common form of head injury, with mild TBIs (mTBIs) making up 75-90% of the TBI severity scale. It’s been suggested that repetitive mild TBIs (rmTBIs) may enhance effects of Alzheimer’s Disease (AD). With dementia linking TBI and AD together, we investigated the memory hub of the brain - the hippocampus. Astrocytes and microglia are two glial cells that respond to neuroinflammation and therefore imaged in hippocampal regions of the 3xTg-AD mouse brain. We hypothesized that AD brain pathology (i.e., neuroinflammation) would be accelerated in 3xTg-AD mice following rmTBIs early in life. Analyses revealed that …

Aging-Related Changes In The Mechanical Properties Of Single Cells, Amarnath Singam, Chandrabali Bhattacharya, Seungman Park

Mechanical Engineering Faculty Research

Mechanical properties, along with biochemical and molecular properties, play crucial roles in governing cellular function and homeostasis. Cellular mechanics are influenced by various factors, including physiological and pathological states, making them potential biomarkers for diseases and aging. While several methods such as AFM, particle-tracking microrheology, optical tweezers/stretching, magnetic tweezers/twisting cytometry, microfluidics, and micropipette aspiration have been widely utilized to measure the mechanical properties of single cells, our understanding of how aging affects these properties remains limited. To fill this knowledge gap, we provide a brief overview of the commonly used methods to measure single-cell mechanical properties. We then delve into …

Protein Nanoparticles As Vaccine Platforms For Human And Zoonotic Viruses, Kush Kumar Pandey, Bikash R. Sahoo, Asit K. Pattnaik

Nebraska Center for Virology: Faculty Publications

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or liveattenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective …

Distinct Expression Patterns Of Hedgehog Signaling Components In Mouse Gustatory System During Postnatal Tongue Development And Adult Homeostasis, Archana Kumari, Nicole E Franks, Libo Li, Gabrielle Audu, Sarah Liskowicz, John D Johnson, Charlotte M Mistretta, Benjamin L Allen

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The Hedgehog (HH) pathway regulates embryonic development of anterior tongue taste fungiform papilla (FP) and the posterior circumvallate (CVP) and foliate (FOP) taste papillae. HH signaling also mediates taste organ maintenance and regeneration in adults. However, there are knowledge gaps in HH pathway component expression during postnatal taste organ differentiation and maturation. Importantly, the HH transcriptional effectors GLI1, GLI2 and GLI3 have not been investigated in early postnatal stages; the HH receptors PTCH1, GAS1, CDON and HHIP, required to either drive HH pathway activation or antagonism, also remain unexplored. Using lacZ reporter mouse models, we mapped expression of the HH …

Identifying Targetable Vulnerabilities To Circumvent Or Overcome Venetoclax Resistance In Diffuse Large B-Cell Lymphoma, Clare M. Adams, Amanda Mcbride, Peter Michener, Irina Shkundina, Ramkrishna Mitra, Hyun Hwan An, Pierluigi Porcu, Christine M. Eischen

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Clinical trials with single-agent venetoclax/ABT-199 (anti-apoptotic BCL2 inhibitor) revealed that diffuse large B-cell lymphoma (DLBCL) is not solely dependent on BCL2 for survival. Gaining insight into pathways/proteins that increase venetoclax sensitivity or unique vulnerabilities in venetoclax-resistant DLBCL would provide new potential treatment avenues. Therefore, we generated acquired venetoclax-resistant DLBCL cells and evaluated these together with intrinsically venetoclax-resistant and -sensitive DLBCL lines. We identified resistance mechanisms, including alterations in BCL2 family members that differed between intrinsic and acquired venetoclax resistance and increased dependencies on specific pathways. Although combination treatments with BCL2 family member inhibitors may overcome venetoclax resistance, RNA-sequencing and drug/compound …

Rewiring The Sex-Determination Pathway During The Evolution Of Self-Fertility., Yongquan Shen, Shin-Yi Lin, Jonathan Harbin, Richa Amin, Allison Vassalotti, Joseph Romanowski, Emily Schmidt, Alexis Tierney, Ronald E Ellis

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Although evolution is driven by changes in how regulatory pathways control development, we know little about the molecular details underlying these transitions. The TRA-2 domain that mediates contact with TRA-1 is conserved in Caenorhabditis. By comparing the interaction of these proteins in two species, we identified a striking change in how sexual development is controlled. Identical mutations in this domain promote oogenesis in Caenorhabditis elegans but promote spermatogenesis in Caenorhabditis briggsae. Furthermore, the effects of these mutations involve the male-promoting gene fem-3 in C. elegans but are independent of fem-3 in C. briggsae. Finally, reciprocal mutations in these genes show …

E6 Inhibtion-Mediated Combinatorial Therapy For Hpv+ Hnscc, Sonia Whang

Loma Linda University Electronic Theses, Dissertations & Projects

High-risk human papillomaviruses (HPV) are the causative agents of virtually all cases of cervical cancer and up to 80% of head and neck squamous cell carcinoma (HNSCC). Current treatment options include chemo- and radiotherapy, though the effectiveness of these therapies is limited by the viral oncoprotein E6, which disrupts apoptotic pathways by binding to and accelerating the degradation of molecules such as p53 and caspase- 8. Our hypothesis was that inhibiting E6 and rescuing the apoptotic mediators would increase the effectiveness of apoptotic agents. The aims of this study were to first, develop an HPV+ HNSCC xenograft model to test …

Deciphering The Contribution Of Microglia To Neurodegeneration In Friedreich's Ataxia, Sydney N. Gillette

Master's Theses

Friedreich's ataxia (FRDA) is the most prevalent inherited ataxia, affecting one in every 50,000 individuals in the United States. This hereditary condition is caused by an abnormal GAA trinucleotide repeat expansion within the first intron of the frataxin gene resulting in decreased levels of the frataxin protein (FXN). Insufficient cellular frataxin levels results in iron accumulation, increased reactive oxygen species production and mitochondrial dysfunction. Tissues most heavily impacted are those most dependent on oxidative phosphorylation as an energy source and include the nervous system and muscle tissue. This is evident in the clinical phenotype which includes muscle weakness, ataxia, neurodegeneration …

Using Rapid Protein Degradation To Determine The Effect Of Runx1 Loss-Of- Function On Dna Damage Accumulation And Repair., Jackriel Pina Morales

Theses and Dissertations

Germline mutations in RUNX1 are associated with familial platelet disorder with a predisposition to myeloid malignancy (RUNX1-FPDMM), in which patients present with low platelet counts,excessive bleeding and bruising, and an increased risk of Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) development throughout their lifetime. To understand how these loss-of-function mutations in RUNX1 drive predispose to malignancy, it is important to develop a detailed understanding of the molecular basis of RUNX1 function. While RUNX1 is a transcription factor, preliminary data from our group and work from others suggests that RUNX1 also interacts with proteins that are critical for DNA damage …

Maackia Amurensis Seed Lectin (Masl) And Soluble Human Podoplanin (Shpdpn) Sequence Analysis And Effects On Human Oral Squamous Cell Carcinoma (Oscc) Cell Migration And Viability, Ariel C Yin, Cayla J Holdcraft, Eamonn J Brace, Tyler J Hellmig, Sayan Basu, Saumil Parikh, Katarzyna Jachimowska, Evelyne Kalyoussef, Dylan Roden, Soly Baredes, Eugenio M Capitle, David I Suster, Alan J Shienbaum, Caifeng Zhao, Haiyan Zheng, Kevin Balcaen, Simon Devos, Jurgen Haustraete, Mahnaz Fatahzadeh, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Maackia amurensis lectins serve as research and botanical agents that bind to sialic residues on proteins. For example, M. amurensis seed lectin (MASL) targets the sialic acid modified podoplanin (PDPN) receptor to suppress arthritic chondrocyte inflammation, and inhibit tumor cell growth and motility. However, M. amurensis lectin nomenclature and composition are not clearly defined. Here, we sought to definitively characterize MASL and its effects on tumor cell behavior. We utilized SDS-PAGE and LC-MS/MS to find that M. amurensis lectins can be divided into two groups. MASL is a member of one group which is composed of subunits that form dimers, …

The Janus Kinase 1 Is Critical For Pancreatic Cancer Initiation And Progression, Hridaya Shrestha, Patrick Rädler, Rayane Dennaoui, Madison Wicker, Nirakar Rajbhandari, Yunguang Sun, Amy Peck, Kerry Vistisen, Aleata Triplett, Rafic Beydoun, Esta Sterneck, Dieter Saur, Hallgeir Rui, Kay-Uwe Wagner

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Interleukin-6 (IL-6)-class inflammatory cytokines signal through the Janus tyrosine kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and promote the development of pancreatic ductal adenocarcinoma (PDAC); however, the functions of specific intracellular signaling mediators in this process are less well defined. Using a ligand-controlled and pancreas-specific knockout in adult mice, we demonstrate in this study that JAK1 deficiency prevents the formation of KRAS^G12D-induced pancreatic tumors, and we establish that JAK1 is essential for the constitutive activation of STAT3, whose activation is a prominent characteristic of PDAC. We identify CCAAT/enhancer binding protein δ (C/EBPδ) as a biologically relevant …

Proteomic Characterization And Cytotoxic Potential Of Proteins From Cuscuta (Cuscuta Epithymum (L.) Crude Herbal Product Against Mcf-7 Human Breast Cancer Cell Line, Umaima Akhtar, Yamna Khurshid, Bishoy El-Aarag, Basir Syed, Ishtiaq A. Khan, Keykavous Parang, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa.

Methods

The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun …

Towards A New Role Of Mitochondrial Hydrogen Peroxide In Synaptic Function, Cliyahnelle Z. Alexander

Student Theses and Dissertations

Aerobic metabolism is known to generate damaging ROS, particularly hydrogen peroxide. Reactive oxygen species (ROS) are highly reactive molecules containing oxygen that have the potential to cause damage to cells and tissues in the body. ROS are highly reactive atoms or molecules that rapidly interact with other molecules within a cell. Intracellular accumulation can result in oxidative damage, dysfunction, and cell death. Due to the limitations of H₂O₂ (hydrogen peroxide) detectors, other impacts of ROS exposure may have been missed. HyPer7, a genetically encoded sensor, measures hydrogen peroxide emissions precisely and sensitively, even at sublethal levels, during …

A Genomics Driven Induced Pluripotent Stem Cell Model Of Infant Acute Lymphoblastic Leukemia - Early Results, Meagan Vacek, Jacqelyn Nemechek, Irina Pushel, Bradley Thornton, Molly Leyda, Priyanka Prem Kumar, Midhat Farooqi, Jay L. Vivian, Erin M. Guest, John M. Perry

Research Days

While the cure rates for pediatric ALL have improved over the decades, infants with ALL (iALL) have not benefitted from these advances and continue to have a devastating prognosis. Unfortunately progress in treatment has also been slowed by inadequate research models. With this project, we address this unmet need by investigating a novel model to understand the cellular and molecular changes that occur during iALL onset and progression.

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Unveiling The Nexus Of Cellular Quality Control: Exploring The Interplay Between Ribosome-Associated Protein Quality Control And Mitochondrial Quality Control Pathways, Foozhan Tahmasebinia

Biological Sciences Theses and Dissertations

In eukaryotic cells, the intricate interplay between cellular quality control mechanisms is crucial for maintaining homeostasis and safeguarding the integrity of vital processes, spanning from macromolecule synthesis to the renewal of entire cellular organelles.

Disruption of these networks can lead to severe diseases such as metabolic disorders, underscoring the interconnected nature and feedback control mechanisms inherent in biological systems, including cellular quality control systems. This interconnectedness extends to the intricate communication between organelles, enabling coordinated functioning and adaptation to changing cellular conditions, particularly in response to stressors.

While the exact mechanisms governing these communications within cellular quality control systems remain …

Characterizing The Expression Of The Sphingosine 1-Phosphate Pathway In Injury And Post-Traumatic Fibrosis, Nicole Cubbage

Masters Theses, 2020-current

Following injury, tissue repair allows for the restoration of the architecture and function of the injured tissue, while tissue replacement is characterized by severely damaged or non-regenerable tissue that is repaired by the laying down of extensive connective tissue, also known as fibrosis. The fibrotic process should be arrested at its early stage to have the greatest impact on preventing or reversing associate sequelae and promoting the regeneration of normal tissue. Sphingosine 1-phosphate (S1P), a metabolic product of cell membrane sphingolipids, has emerged as a pathway that may be involved in fibrosis. Most of S1P’s actions are mediated through the …

Immunopathogenesis Of Post-Infectious Hydrocephalus, Sascha Powers Bernier

Honors Scholar Theses

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain ventricles. In post-infectious hydrocephalus (PIH) cases, the condition presents challenges in understanding the immune response. PIH is a complex condition, often persisting after the initial infection is treated and thus requiring a deeper understanding of the immune mechanisms involved in its development. This thesis will explore the immunopathogenesis of PIH, elucidating the relationship between the immune response and neurological complications that would succeed infection. The immune response of PIH includes a series of events, beginning with the activation of immune cells and finishing with the release …

Protein Oxidation In Aging And Alzheimer’S Disease Brain, Rukhsana Sultana, D. Allan Butterfield

Markey Cancer Center Faculty Publications

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer’s disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Identifying The Molecular Determinants Of Lung Metastatic Adaptation In Prostate Cancer, Grace M. Waldron

Theses & Dissertations

Prostate cancer (PC) stands as the primary diagnosed cancer in men in the US at approximately 299,010 cases in 2024 and ranks second globally, posing a significant public health challenge. Clinical presentations vary widely, from indolent to aggressive forms, necessitating stage-specific treatment regimens. Understanding its metastatic nature is critical due to the impact of cancer cell dissemination on disease morbidity, with bone and visceral organs serving as key sites of metastasis. Despite bone metastasis being the most common site for metastasis, visceral metastases at sites such as the liver and lungs correlate with poorer survival, emphasizing the role of microenvironmental …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Efficacy Of Mcl-1 Inhibitors In Multiple Myeloma Cells Resistant To Bortezomib, Emily Nelson, Omar S. Al-Odat, Sabrina M. Paparo, Daniel A. Guirguis, Gabriella Yao, Manoj Pandey, Subash Jonnalagadda, Tulin Budak-Alpdogan

Rowan-Virtua Research Day

Multiple myeloma (MM) is a type of cancer that affects plasma B cells. Patients with MM often experience frequent relapses and can develop resistance to drugs. As a medical researcher, it is important to understand the role of Mcl-1 in preventing intrinsic apoptosis and drug resistance. Mcl-1 belongs to the anti-apoptotic subgroup of Bcl-2 family proteins and plays a crucial role in these processes. Mcl-1 plays a crucial role in driving disease progression and contributing to drug resistance in MM. It has been observed that there is an increased expression of Mcl-1 in 52% of patients with MM during diagnosis, …

Investigating The Therapeutic Potential Of Soursop In Treating Hematologic Malignancies, Sabrina Marie Paparo, Rebeca Mendoza, Robert Chitren, Omar Al-Odat, Emily Nelson, Subash Jonnalagadda, Roger Strair, Manoj Pandey

Rowan-Virtua Research Day

Acute Myeloid Leukemia (AML) and Multiple Myeloma (MM) are hematologic malignancies that originate in the bone marrow and account for approximately 1.3% and 2% of cancer cases, respectively. AML is characterized by an accumulation of myeloblasts, or immature myeloid cells, that have the potential to spread to the peripheral blood. There is an uncontrolled proliferation of plasma cells in the bone marrow in MM. While the current treatment options for both AML and MM show promise in achieving initial remission, it is unfortunately common for patients to experience relapse and develop drug resistance. There is a theory that relapse and …

Intra-Accumbens Microinfusion Of The Dopamine D3 Receptor Partial Agonist (±)Vk4-40 Does Not Affect Basal Locomotion In Mice, Yeonwoo Sim, Nicole M. Hinds, Amy Hauck Newman, Daniel F. Manvich

Rowan-Virtua Research Day

The opioid epidemic remains a pressing public health crisis, prompting the search for alternative pharmacotherapies for Opioid Use Disorder (OUD). This study explores the potential of the dopamine D3 receptor (D3R) partial agonist, (±)VK4-40, as a novel treatment option. We investigated the impact of intra-nucleus accumbens (NAc) microinfusion of VK4-40 on basal locomotion in mice. Results indicate that VK4-40 did not significantly alter basal locomotion, suggesting that its therapeutic effects may not be mediated through disruptions in generalized motor function. Future research will focus on elucidating the neuropharmacological mechanisms underlying VK4-40's therapeutic actions and exploring its effects on psychostimulant-induced hyperlocomotion. …

The Effect Of Diabetes Mellitus On Differentiation Of Mesenchymal Stem Cells Into Insulin-Producing Cells, Mohamed M. Kamal, Omar I. Badr, Shohda A. El-Maraghy, Heba R. Ghaiad

Pharmacy

Background

Diabetes mellitus (DM) is a global epidemic with increasing incidences. DM is a metabolic disease associated with chronic hyperglycemia. Aside from conventional treatments, there is no clinically approved cure for DM up till now. Differentiating mesenchymal stem cells (MSCs) into insulin-producing cells (IPCs) is a promising approach for curing DM. Our study was conducted to investigate the effect of DM on MSCs differentiation into IPCs in vivo and in vitro.

Methods

We isolated adipose-derived mesenchymal stem cells (Ad-MSCs) from the epididymal fat of normal and STZ-induced diabetic Sprague–Dawley male rats. Afterwards, the in vitro differentiation of normal-Ad-MSCs (N-Ad-MSCs) and …