Disease Modeling

A New Way for How You Model Human Biology

Disease modeling, specifically using induced Pluripotent Stem Cells (iPSCs), has transformed how researchers understand and approach human biology. This innovation offers unprecedented possibilities for in vitro models of neurodegenerative diseases, among others, providing enhanced precision and applicability.

Why Disease Modeling with Human iPSC-derived Cells?

The concept of iPSC disease modeling traces its roots back to 2006 when Shinya Yamanaka first discovered the ability to reprogram somatic cells into pluripotent stem cells. This breakthrough unlocked numerous benefits, ranging from creating more representative models of cells to drug screening and therapeutic discovery.

What are required?

iPSC disease modeling involves reprogramming somatic cells from patients with a specific disease into pluripotent stem cells. These iPSCs retain the patient's genetic makeup, allowing scientists to differentiate them into any cell type for study, including those implicated in neurodegenerative diseases like ALS and Alzheimer's. This process enables more accurate in vitro modeling and allows us to better understand disease pathogenesis, drug response, and potentially develop treatment strategies.

Advantages Against Other Alternative Modeling Methods

iPSC disease modeling presents unique advantages over other traditional methods, such as primary cells, other cell lines, and animal models. Primary cells are limited by their short lifespan and variable performance, while other cell lines often lack the genetic background of the disease. Animal models, while useful, cannot fully replicate human biology and disease states.

iPSC-derived models, on the other hand, overcome these barriers. They are patient-specific, enabling the recapitulation of complex genetic backgrounds and diseases. As a result, iPSC models offer superior physiological relevance in studies related to neurodegenerative diseases, such as ALS (using ALS iPSCs) and Alzheimer's disease (using stem cells).

Challenges in Exploring Therapeutic Discovery with iPSC-based Disease Modeling

While iPSC disease modeling presents significant advantages, several challenges remain. These include maintaining and differentiating iPSC cultures, ensuring robustness and reproducibility of the models, and sourcing disease-specific iPSC lines.

How Elixirgen Scientific iPSC Differentiation Technology Could Help

Elixirgen Scientific provides tailored solutions to mitigate these hurdles. They assist in pinpointing which iPSC banks might hold the disease-specific lines relevant to the client's interests and aid in streamlining the acquisition process from these banks. However, it's important to keep in mind that there could be unexpected obstacles along the way (check this page to learn about our experiences). Leveraging their proficiency in iPSC culture and differentiation, Elixirgen Scientific is capable of creating a wide array of downstream assays with consistent outcomes. Their bespoke differentiation technology further empowers the creation of various cell types, leading to a more thorough approach in disease modeling.

Disease Modeling Examples

Elixirgen Scientific's differentiation technology has been instrumental in a number of notable projects. For instance, it was used to model Alzheimer's disease with iPSC-derived neurons. This enabled a deeper understanding of the disease and contributed to stem cell research for Alzheimer's.

In another study, ALS was modeled using TDP-43 and SOD1 mutant lines, revealing key aspects of disease progression and potential therapeutic targets. Similarly, Duchenne Muscular Dystrophy (DMD) was modeled using patient and CRISPR corrected lines, providing valuable insights into the disease's pathology.

Through these examples and others, it is clear that disease modeling with iPSC-derived cells is a powerful tool for studying human biology, especially in the context of neurodegenerative diseases. With technologies like those provided by Elixirgen Scientific, researchers can continue to advance our understanding of these complex conditions and pave the way for innovative therapeutic solutions.

Alzheimer's Disease

Disease Modeling with Induced Pluripotent Stem Cells (iPSCs)

Mixed neurons differentiated from both a control patient and an Alzheimer’s Disease (AD) affected patient using Elixirgen's mixed neuron Sendai virus kit (A) qRT-PCR data 15 days post differentiation (B)  ELISA data shows amounts of Aβ and Tau protein after 6 weeks of culture

Amyotrophic lateral sclerosis (ALS)

ALS Disease Modeling with Cholinergic neurons differentiated to a Healthy Control and ALS patient from iPSC.

Cholinergic neurons differentiated, using Elixirgen's CH-SeV differentiation kit, from ALS patient-derived iPSCs (with TDP-43 mutation) show aggregation of TDP-43 in cytoplasm

Myotonic Dystrophy Type 1

DMD and CRISPR corrected iPSC-derived Skeletal Muscle Cells

Skeletal muscle cells differentiated (using Elixirgen's Differentiation Service) from Myotonic Dystrophy Type I  (DM-03) and gene-corrected (J-6) patient-derived iPSCs provided by a customer. Cells derived from the DMD1 patient exhibit disease-associated phenotypes (on DM-03 nuclei, A, C). Loss of disease-associated RNA foci was observed after correction of the mutation (on J-6 nuclei: B, D).

Source: Wang et.al., Molecular Therapy (Nov 2018)

How Can We Help?

List of diseases and mutations.

Transform how you study disease with Quick-Tissue™ technology
With Quick-Tissue™ technology, you can study disease state from multiple angles in vitro. Thanks to advance in iPSC reprogramming technology, there are thousands of iPSC lines available for your disease study. Look through the iPSC line database below to find out your diseases in interest exist. The database also lists identified mutant genes. Feel free to reach us to how we can help getting differentiated cells derived from iPSC lines in your interest.

DiseaseMutant genes (# of iPSC lines)Number of total patient iPSC lines
ABCA1 heterozygousABC1 (2)2
AbetalipoproteinemiaMTP (2)2
Acromesomelic dysplasiaNPR2 (1)1
Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD)1
Adrenoleukodystrophy (ALD)1
Adult-onset Still’s disease (AOSD)1
Age-related macular degeneration (AMD)121
Aicardi syndrome1
Alexander diseaseGFAP (3)6
Allergic granulomatous angiitis1
Alzheimer's disease (AD)APOE (10), APOE4 (3), APP (4), C9ORF (1), CD33 (2), MAPT (2), PSEN1 (14), PSEN2 (1), TBK1 (1), TREM2 (3)180 (Available Differentiated cells)
Alzheimer's disease (AD) (Gene-edited)APP (6), PSEN1 (8)14
Alzheimer's disease (AD) (familial)APP (3), APPV7171 (4), PSEN1 (1), PSEN2 (1)11
Amyotrophic lateral sclerosis (ALS)ASYMPTOMATIC C9ORF72 CARRIER (1), C9ORF72 (46), FIG4 (1), FUS (3), SETX (1), SETX, SOD1 (1), SOD1 (36), SOD1 > D90A (1), TARDBP (5), VCP (1)532
Anemia (phenotype)1
Angelman syndromeUBE3A (2)10
Aplastic anemia3
Arrhythmogenic right ventricular cardiomyopathy2
Associated pulmonary arterial hypertension18
Atrial fibrillation14
Atrial tachycardia1
Autism spectrum disorder (ASD)110 (Available Differentiated cells)
Autoimmune hemolytic anemia (AHA) / Idiopathic warm (AHA)1
Bardet-biedl syndrome22
Batten disease (cln3)CLN3 (23)23
Batten disease (cln6)8
Behçet’s disease2
Beta thalassemiaHBB (2)2
Bethlem myopathy2
Bilateral frontoparietal polymicrogyriaGPR56 (1)1
Bipolar disorder30
Blinding eye disease18
Borderline NASH (fatty liver disease)2
Breast cancerBRCA1 (3)3
Brugada syndrome6
Buerger’s disease1
Carpal tunnel syndrome18
Catecholaminergic polymorphic ventricular tachycardiaRYR2 (2)2
Ccanavan DiseaseASPA (1)1
Cchoroideremia (CHM)CHM (1), NGLY1 (1)4
Cerebral creatine deficiency syndrome 1 (CCDS1)SLC6A8 (1)1
Cerebral palsy (CP)19
Cerebrovascular disease4
Ceroid lipofuscinosisCHM (1), CLN2 (1)2
Charcot-Marie-Tooth diseaseFIG4 (1), MFN2 (10), MPZ (2), PMP22 (7), VCP (1)22
Chromosome 16p11.2 deletion syndrome5
Chronic inflammatory demyelinating polyneuropathy (CIDP)2
Chronic myeloid leukemia1
Congenital disorder of deglycosylation (CDDG)CFTR (1)1
Congenital heart block2
Congenital ichthyosis / Ichthyosis syndrome1
Congenital insensitivity to pain with anhidrosis (CIPA)2
Congenital myasthenic syndromeGFPT1 (1)7
Congenital myopathyMTM11 (1)1
ControlC9ORF72 (5), CCR5 (1), GFAP CORRECTED (2), HBB (1), HD (5), HNF1A (1), MECP2 (2), NGN2 (2), SNCA (1), SOD1 > D90A CORRECTED (1), TAF1 VARIANT CORRECTED (4)25
Coronary artery disease43
Corticobasal degeneration (CBD)1
Crohn's disease3
Crow‐Fukase syndrome2
Cystic Fibrosis (CF)DMPK (1)1
DMRV / GNE myopathy2
Danon disease1
Definite NASH (fatty liver disease)32
DiabetesHNF1A (2)3
Diabetes mellitus60
Diabetes mellitus type II12
Diabetes type I21
Diabetes type II95
Diabetes type unknown4
Diabetic retinopathy (DR)32
Diamond-Blackfan anemia1
Dilated cardiomyopathy (DCM)303
Distal Myopathy3
Down syndrome47,XX,+21 (4), 47,XY,+21 (3)8
Dravet syndromeSCN1A (11)11
Drug-induced liver injury (DILI)4
Duchenne Muscular dystrophy (DMD)DMD (1)2
Dystrophia myotonica 1 (DM1)DMPK (1)1
Ehlers-Danlos syndromeCOL3A1 (1)2
Eosinophilic granulomatosis with polyangiitis (EGPA)1
Eosinophilic sinusitis1
Epidermolysis bullosa1
EpilepsyALG13 (1), GABRA1 (1), KCNC1 (1), PCDH19 (2), SCN2A (1)57 (Available Differentiated cells)
Fabry disease3
Facioscapulohumeral muscular dystrophy 1 (FSHD1)LRIF1 (1)6
Familial Mediterranean fever1
Fatty liver disease - steatosis (not NASH)2
Focal cortical dysplasia (FCD)2
Focal segmental glomerulosclerosis20
Fragile X syndromeFMR1 (4)4
Friedreich ataxia 1 (FRDA)FXN (2)2
Frontotemporal degenerationC9ORF72 (4), GRN (4), MAPT (10), PGRN (2), VCP (1)25
Frontotemporal dementia (FTD)C9ORF72 (6), MAPT (15)30
Frontotemporal lobar degeneration (FTLD)2
Gaucher diseaseGBA (1)2
Giant cell arteritis (GCA)2
Glut1 deficiency syndrome 1 (Glut1DS1)SLC2A1 (1)1
Glycogen storage disease / GSD type V (muscle glycogen phosphorylase deficiency)1
Glycosylphosphatidylinositol(GPI) anchor deficiency3
Granulomatosis with polyangiitis (GPA)1
Hemiconvulsion-hemiplegia-epilepsy syndrome2
Hepatitis C (HCV)91
Hereditary dystonia1
Homozygous familial hypercholesterolemiaLDLR (6)6
Hunter syndrome2
Huntington's disease (HD)HD (14), HTT (36), IT15 (1), SMN1 (1)58
Hurler syndromeIDUA (1)1
Hutchinson-gilford progeria syndrome (HGPS)2
HyperalphalipoproteinemiaSR-BI (2)2
Hypertrophic cardiomyopathyTNNT2 (1)83
Idiopathic aplastic anemia1
Idiopathic pulmonary arterial hypertension16
Idiopathic pulmonary fibrosis (IPF)182
Idiopathic thrombocytopenic purpura1
IgG4-related disease1
IgG4-related thyroid disease1
Inappropriate sinus tachycardia1
Infantile neuroaxonal dystrophy (INAD)PLA2G6 (5)5
Intellectual disability (ID)60
Interstitial lung disease1
Isaacs syndrome1
Isogenic control3
Kearns-sayre syndrome (KSS)1
Krabbe diseaseGALC (1)1
Landau-Kleffner syndrome1
Left ventricular hypertrophy15
Left ventricular non-compaction cardiomyopathy10
Lennox-Gastaut syndrome (LGS)2
Lesch-nyhan syndrome (LNS)HPRT1 (1)1
Lewy body dementia8
Lewy body dementia (LBD)1
Limb-girdle muscular dystrophyDYSF (5)5
Limb-girdle muscular dystrophy (LGMD2b)DYSF (15)15
LissencephalyDCX (1)1
Long QT syndrome3
Long QT syndrome (familial)13
Long QT syndrome 1 (LQT1)3
Long QT syndrome 2 (LQT2)KCNH2 (1)1
Long QT syndrome 3 (LQT3)SCN5A (1)1
Malignant rheumatoid arthritis (MRA)1
Mental illnessDISC1 EXON 8 WILD-TYPE (2)2
Mental retardationCHAMP1 (2), SYNGAP1 (1)3
Mesial temporal lobe epilepsy with hippocampal sclerosis2
Microscopic polyangiitis (MPA)1
Mild left ventricular hypertrophy1
Miller-dieker lissencephaly syndrome (MDLS)1
Mitochondrial diseases1
Mixed Connective-Tissue Disease (MCTD)1
Monogenic diabetes13
Mortor dominant1
Moyamoya disease3
Mucopolysaccharidosis (MPS)SGSH (1)3
Multifocal motor neuropathy (MMN)1
Multiple sclerosis (MS)4
Multiple system atrophy (MSA)6
Muro disease (Kii ALS/PDC)3
Muscular dystrophyDMD (5), LAMA2 (1), POMT2 (1)9
Myasthenia Gravis (MG)1
Myocardial infarction18
Myoclonic epilepsyCHD2 (1)1
Myotonic dystrophyCNBP (4), DMPK (1)9
Nescav syndromeKIF1A (5)6
Neurodegeneration with brain iron accumulation 5 (NBIA5)WDR45 (1)1
Neurodevelopmental disorderDHPS (1)1
Neurofibromatosis type1 (NF1)1
Neurofibromatosis type2 (NF2)1
Neuromyelitis Optica4
Neuromyelitis Optica Spectrum Disorders (NMOSD)1
Neuronal migration disorderPIK3R2 (1)3
NeuropathyGARS (2), SCN9A (6)39
Niemann-pick diseaseNPC1 (1), SMPD1 (3)5
Non-als motor neurone disease1
Ohtahara syndromeSTXBP1 (1)1
Ornithine transcarbamylase deficiency (OTCD)1
Osteogenesis imperfecta type iv (OI4)COL1A2 (1)1
PACS1 (Schuurs-Hoeijmakers) syndromePACS1 (2)2
Pain agnosiaSCN11A (2)2
ParkinsonismGBA (2), LRRK2 (6), MAPT (1), PARK2 (4), PINK1 (1), SNCA (3)26
Parkinson’s disease (PD)GBA (18), LRRK2 (8), SNCA (9)99
Paroxysmal nocturnal hemoglobinuria (PNH)1
Pemphigoid (including epidermolysis bullosa acquisita)2
Periodic paralysis1
PhenylketonuriaPAH PAH (1)2
Pick's disease1
Pitt-hopkins syndrome (PTHS)TCF4 (1)1
Polyarteritis nodosa (PAN)2
Pompe’s disease (adult type)1
Primary antiphospholipid syndrome2
Primary erythromelalgiaSCN9A (2)4
Primary immunodeficiency syndrome3
Primary lateral sclerosis (PLS)7
Primary open angle (POAG)20
Primary progressive aphasia (PPA)1
Progressive multifocal leukoencephalopathy (PML)1
Progressive supranuclea palsy (PSP)1
Prolonged QT interval6
Pulmonary arterial hypertension ALK1 (2), BMPR2 (4)6
Pulmonary atresia1
Pustular psoriasis1
Pyogenic sterile arthritis / Pyoderma gangrenosum and acne syndrome1
Rasmussen encephalitis2
Relapsing polychondritis (RP)1
Resolved systolic anterior motion1
Restrictive cardiomyopathy1
Retinitis pigmentosa5
Rett syndromeFOXG1 (5), MECP2 (6), SHANK3 (1)15
Right ventricular outflow tract premature ventricular contractions2
Ring chromosome 20 syndrome2
Sanfilippo syndrome / MPS IIIC (acetyl-CoA:heparan-α-D-glucosaminide N-acetyltransferase deficiency)1
Semantic Dementia2
Severe combined immunodeficiencyADA (2)2
Sickle cell anemiaHBB (55)55
Sjögren’s syndrome1
Skeletal displasia4
Small atrial septal defect1
Smith-magenis syndrome (SMS)1
Spinal muscular atrophySMN1 (14)18
Spinal-Bulbar Muscular Atrophy (SBMA)10
Spinocerebellar Degeneration14
Spinocerebellar ataxia type 12
Spinocerebellar ataxia type 3ATXN3 (4)4
Spondylometaphyseal displasia2
Stevens-Johnson syndrome (SJS)1
Sturge-Weber syndrome1
Subacute sclerosing panencephalitis (SSPE)2
Systemic amyloidosis2
TNF receptor-associated periodic syndrome1
Takayasu arteritis3
Tangier diseaseABC1 (2), ABCA1 (4)6
Tay-sachs disease (TSD)HEXA (1)1
Thrombotic thrombocytopenic purpura (TTP)1
Tricuspid atresia1
Tuberous sclerosisTSC2 (2)3
Ventricular tachycardia5
Vertebrobasilar insufficiency(VBI)1
Vici syndrome (VICIS)EPG5 (1)1
Werner syndrome1
West syndrome1
Wilson’s disease4
Wolfram syndrome1
Wolman disease1
X-linked creatine transporter deficiency1
X-linked dystonia ParkinsonismTAF1 VARIANT (34)34
Xeroderma pigmentosum2