Growth factors and cytokines for organoid research

Organoids are miniaturized models in vitro that mimic various aspects of the complex structure and function found in living tissues of our body. The organoids can be developed in vitro from the relevant precursor cell if cultured under specific conditions like the relevant cellular matrix and the presence of a cocktail of growth and differentiation factors. They serve as valuable tools for studying the mechanisms involved in tissue development, regeneration, and repair in humans. Additionally, they have far reaching applications in diagnostics, disease modeling, drug discovery including drug testing and personalized medicine.

Adult stem cells-derived organoids

Endometrial organoids are derived from epithelial cells. Endometrial epithelial fragments that consist of glandular and luminal cells, self-organize to form three-dimensional gland-like structures within Matrigel scaffolds.  These organoids were more recently established from human endometrium with promising features to better mimic the receptive phase. Endometrial organoids show a better long-term expandability and the capability to preserve the structural and functional characteristics of the human endometrial tissue. The organoids as a three-dimensional model maintain a fair responsiveness to steroid hormones in vitro and replicates key morphological features of the receptive endometrium in vivo, including pinopodes and pseudostratified epithelium.

Literature: M.Y. Turco et al., Nat Cell Biol . 2017 May;19(5):568-577

Signal factors:

human EGF

human FGF-10

human HGF

human Noggin

human R-Spondin 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

The fallopian tubes are a pair of muscular tube-like organs that are often overlooked in basic research. Their primary functions are to catch ovulating oocytes from the adjacent ovaries. It has an important function in physiological and pathological processes. Very recently a novel organoid model of the human fallopian tube that was developed to reflect the compartmentalization and heterogeneity of the tissue composition. Validation was done for this organoid’s by its molecular expression patterns, cilia-driven transport function and structural accuracy and reproducibility. Finally this organoid model was precision-engineered to match the human microanatomy on a relative high level. This organoid model constitutes the basis for future studies investigating disease states of the fallopian tubes.

Literature: A. J Crawford et al., bioRxiv. 2023 Jun 7:2023.

Signal factors:

human EGF

human FGF-10

human Noggin

human R-Spondin 1

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Gallbladder organoids, recently developed three‐dimensional (3D) culture technologies, faithfully recapitulate the architecture and function of primary tissues. Patient‐derived organoids (P-DOs) developed from individual tumour patients can indefinitely expand and accurately recapitulate the morphological and molecular features of the original tumour. Uo to now, tumour organoids have been established for a wide range of cancer types, such as colon, pancreatic, liver and prostate tumours, These P-DOs were subsequently employed for drug screening and tailored treatment in cancer therapy.  By using sophisticated organoid culture technology, it is possible to establish organoids derived from human normal gallbladder, benign gallbladder adenoma (GBA) and gallbladder carcinoma (GBC). So far gallbladder organoid culture technology have been used to identify novel drug candidates to suppress growth of GBC organoids.

Literature: N. Lugli et al.,EMBO Rep . 2016 May;17(5):769-79

Signal factors:

human EGF

human FGF-10

human HGF

human Noggin

human R-Spondin 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

The study of human intestinal biology in healthy and diseased conditions has always been challenging. Primary obstacles have included limited tissue accessibility, inadequate in vitro maintenance and ethical issues. Three-dimensional, multicellular culture systems have been developed which incorporate the main cell types and key functional features of the intestinal epithelium, providing direct relevance to the in vivo tissue. Intestinal organoids are self-organized three-dimensional structures that partially recapitulate the identity, cell heterogeneity and cell behaviour of the original tissue in vitro. Intestinal organoids make it easier to get in vivo insight from in vitro experiments. This includes the capacity of stem cells to self-renew, as well as to differentiate towards major intestinal lineages. Over the past decade, the use of human organoid cultures has been instrumental to model human intestinal development, homeostasis, disease, and regeneration. Intestinal organoids can be derived from pluripotent stem cells (PSC) or from adult somatic intestinal stem cells (ISC). Both types of organoid sources harbour their respective strengths and weaknesses.

Literature: T. Sato et al., 2011 Gastroenterology . 2011 Nov;141(5):1762-72

Signal factors:

human EGF

human Noggin

human R-Spondin 1

human Wnt3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Despite the predominant use of 2-D culture of renal tubular epithelial cells (RTECs), this model might not fully replicate both the morphology and physiology of three-dimensional (3-D) kidney tubules in vivo and fails to demonstrate appropriate injury responses to drug-induced nephrotoxicity in vitro. Therefore, human urine-derived stem cells can be differentiated into renal tubular epithelial cells in three-dimensional (3-D) culture after being induced by a kidney extracellular matrix. Levels of kidney specific proteins like CYP2E1 and KIM-1 in 3-D organoids were significantly increased in response to acetone and cisplatin. This 3-D culture system provides an alternative tool for nephrotoxicity screening and research. Differentiating stem cells to renal tubule epithelial cells has proven challenging despite extensive investigation. Studies demonstrated that tissue-specific extracellular matrix (ECM) plays a major role in inducing and retaining the phenotypic characteristics of specific primary cells in vitro.

Literature: F.A.Y YengejCells . 2020 May 26;9(6):1326.

Signal factors:

human EGF

human FGF-10

human R-Spondin 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Liver

Hepatic organoids (liver cells) are functional three-dimensional (3D) in vitro models of the liver and serve as a novel platform to address diverse research questions pertinent to hepatic development and regeneration, detoxification and metabolism studies, liver disease modelling, and adult stem cell biology. The use and implementation of hepatic  organoids has an immense potential in the fast advancing field of hepatic research. Particuar under conventional culture conditions hepatocytes in tend to dedifferentiate . Hepatic organoids are often cultured within a extracellular matric as scafold with a combination of growth factors to facilitate growth, formation and differentiation into organoids. For successful differentian, the expression of albumin is an established indicator for the hepatic differentiation. Hepatic organoids has opened the possibility to establish disease models for studies based in gene and cell therapy in liver cancer or other liver diseases.

Literature: Huch et al., Cell. 2015 Jan 15;160(1-2):299-312

Signal factors:

human EGF

human FGF-10

human HGF

human Noggin

human R-Spondin 1

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Lung

Lung organoids are an especially powerful tool for the development of anti-infectiva. They are further used for high-throughput drug screening and secondary screens with human primary cell aggregates. They provide the possibility to study complex respiratory-related diseases and processes.  These lung organoids contain several-types of tissue-specific cell types, like microvessel lung endothelial cells, epithelial cells and mesenchymal cells. The fine structure of these lung organoids and the branching architecture are resembling on lung regions like the alveolar and airway regions within the lung tissue.

Literature: A.J. Miller Nat Protoc . 2019 Feb;14(2):518-540

Signal factors:

human Activin A

human FGF-4

human FGF-10

human Noggin

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Mammary

The mammary gland (MG) is a dynamic organ whose structure and function change throughout the female reproductive cycle. These changes are strictly regulated because any aberrations can lead to organ dysfunction or disease. Three-dimensional (3-D) mammary organoid culture has become an important tool in mammary gland biology and enabled invaluable discoveries on pubertal mammary branching morphogenesis and breast cancer. These organoid cultures can maintain some of the cellular heterogeneity observed in the tissue of origin, including the presence of stem/progenitor and differentiated cell types. In addition, when grown in the presence of specialized growth factor cocktails and cellular matrix, long-term culture can be achieved. This feature is being leveraged to create organoid "biobanks" for disease modeling and drug screening

Literature: N. Sachs et al., Cell. 2018 Jan 11;172(1-2):373-386

Signal factors:

human EGF

human FGF-7/KGF

human FGF-10

human Heregulin beta 1/Neuregulin (NRG-1)

human Noggin

human R-Spondin 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Oral mucosa

The oral mucosa, is a highly compartmentalized tissue and can be subdivided into the buccal mucosa, gingiva, lips, palate, and tongue. Its uppermost layer, the oral epithelium, is maintained by adult stem cells throughout life. Complementary to 2D cellular culture models is the so-called organoid technology, where adult stem cells are embedded into an extracellular matrix (ECM)-rich hydrogel and provided with a culture medium containing a defined cocktail of growth factors. Primary epithelial cells are isolated from tongue tissue, embedded into an ECM hydrogel, and cultured in a medium containing: epidermal growth factor (EGF), R-spondin, and fibroblast growth factor (FGF) 10. Within 1-2 weeks of initial seeding, the resulting organoids can be passaged for further expansion and cryopreservation. These methods may serve as a tool to investigate oral epithelial stem cell behavior ex vivo in a reductionist manner.

Literature: E. Driehuis et al., Proc. Natl. Acad. Sci. U S A. 2019;116:26580–26590

Signal factors:

human EGF

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human FGF-10

human Noggin

human R-Spondin 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Oesophagus

Recently culture conditions for 3-dimensional mouse and human esophageal organoids from explants have be established.  One possible application of this experimental platform is towards personalized medicine for notch3-mediated squamous cell differentiation and other mechanisms for investigations of inflammatory conditions. The 3-dimensional (3D) organoid system is a cell-culture based, novel, and physiologically relevant biologic platform. With a small number of cells isolated from tissues or cultured cells as starting materials, 3D organoids are grown and passaged in basement membrane matrix (extracellular matrix). Organoids provide insights into the roles of molecular pathways and niche factors essential in intestinal stem cell renewal, proliferation, and differentiation. Although 3D organoids have been generated from broad tissue types, the application of this technique to human stratified squamous epithelia remains elusive.

Literature: Liu H, Wang X., J Mol Med (Berl). 2023 Aug;101(8):931-945

Signal factors:

human EGF

human FGF-10

human Noggin

human R-Spondin 1

human Wnt3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Pancreatic duct

The pancreas represents an important organ but it is hard to study with the traditionell approaches To fill this gap, many models have been generated. More recently, organoids have been proposed as a novel model for the evaluation of pancreatic-related diseases such as pancreatic malignancy, diabetes, and pancreatic cystic fibrosis. Since the first organoid created by T. Sato et al. presented a differentiated cell type through the use of adult stem cells, organoid technology has inspired many scientists worldwide to make great advancements in research. Many cell types have been confirmed to create organoids, including the stomach, intestine, colon, liver, prostate and pancreas. The first pancreatic organoids were generated in 2013. The advantages of organoids include the relative harmlessness of extracting tissue samples, and the feasibility of applying them to humans. This technology allows to significantly reduce ethical compliance issues and increase the potential for organoid applications.

Literature: SF Boj et al., Cell. 2015;160:324–338

Signal factors:

human EGF

human FGF-10

human Noggin

human R-Spondin 1

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Stomach

To ensure an always functional mucosa of the stomach, a continuous self-renewal of the epithelium is required. Gastric organoids can be established from adult stem cells of primary tissue, embryonic stem cells or induced pluripotent stem cells. Organoids are bio-cellular models constructed in vitro using stem cell culture and 3D cell culture techniques, which are the latest research hotspots. The proliferation of stem cells in vitro is the key to gastric organoid models, making the cell subsets within the models more similar to in vivo tissues. Organoids are cellular aggregates cultured in three-dimensions within a special matrix that grow with similar characteristics as their tissue-of-origin. Due to their self-renewal and proliferative capacity, organoids can be maintained long term in culture and expanded in many cases in an unlimited fashion. For example, patient-derived organoid (PDO) libraries function as living biobanks, allowing the in-depth analysis of tissue specific function, development and disease. The recent successful establishment of gastric cancer PDOs opens up new perspectives for multiple translational clinical applications.

Literature: S. Bartfeld and H. Clevers, J Vis Exp 2015 Nov 12:(105):53359

Signal factors:

human EGF

human FGF-10

human Noggin

human R-Spondin 1

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Urothelium

Recently, cancer biologists have turned to 3D culture methods, which shows some advantages as compared with traditional models. Cells could form multicellular complex (spheroids) when they were maintained in suspension or embedded in some scaffold (e.g. extracellular matrix). Organoid culture, instead, implies formation of 3D compositions that contains several type of epithelial cells. These structures are formed from single adult epithelial stem cell and allows to study the multicellular composition of tissue epithelia in a dish. Organoids derived from adult stem cells can be used to directly model hereditary diseases such as cancer. Cancer can be displayed in organoid based on the principles of bottom-up model: when normal cells specifically modified to became more tumorigenic.  Using established urothelial organoid system scientists have developed a bottom-up model of bladder cancer. Finally, it can be used for limited drug testing on organoids from the bladder cancer biobank.

Literature: Mullenders et al., PNAS. 2019 Mar 5;116(10):4567-4574

Signal factors:

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human FGF-7/KGF

human FGF-10

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Pluripotent stem cells-derived organoids

Blood vessel organoids are an important in vitro model to understand the underlying mechanisms of human blood vessel development and for toxicity testing or high throughput drug screening. One report mentioned the use of human induced pluripotent stem cell (hiPSC)-derived vascular organoid cells as a new cell source for a new human macrovessel model. A separation protocol is developed to obtain monocultures of organoid-derived endothelial cells and mural cells from hiPSC vascular organoids. HiPSC-derived vascular organoids can be used as a source of functional, flow-adaptive vascular cells for the creation of 3D-scaffold based human macrovascular models. In other approaches with human induced pluripotent stem cells the formation of a circular layer of angioblasts around days 5–6 appears. Induced by VEGF application, CD31+ vascular endothelial cells appear within this vasculogenic zone at approximately day 7 of organoid culture. Finally, this organoid model recapitulates human vasculogenesis, angiogenesis as well as blood vessel wall maturation and therefore represents an easy and cost-effective tool to study all steps of blood vessel development and maturation directly in the human setting without animal experimentation.

Literature: Schmidt et al., Organoids 2022, 1, 41–53.

Signal factors:

human BMP-4

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human VEGF-A121

human VEGF-A145

human VEGF-A165

human VEGF-A165b

human VEGF-A165b with Biotin

human VEGF-A189

human VEGF-A206

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Lymph vessel

The lymphatic system is involved in various biological processes, including fluid transport from the interstitium into the venous circulation, lipid absorption, and immune cell trafficking. Despite its critical role in homeostasis, lymphangiogenesis (lymphatic vessel formation but not blood vessel formation) is less widely studied than its counterpart, angiogenesis (blood vessel formation). In one report, populated thick collagen sheets with human lymphatic endothelial cells, combined with supporting cells (mural cells) and blood endothelial cells, and the authors examined lymphangiogenesis within the resulting constructs. Coculture of lymphatic endothelial cells with the appropriate supporting cells (mural cells) and intact PDGFR-β signaling proved essential for the lymphangiogenesis process. Implantation of the engineered lymphatic constructs into a mouse abdominal wall muscle resulted in anastomosis between host and implant lymphatic vasculatures, demonstrating the engineered construct's potential functionality in vivo.

Literature: Landau et al., PNAS, 2021, 118, no.31

Signal factors:

human VEGF-C

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Cardiac

Cardiac organoids are three-dimensional in vitro models with a cellular composition and structural organization that is representative of the human heart. They resemble the human heart with cardiac cell progenitors.  Human iPSC-derived cardiac organoids are differentiated from human iPSCs using specific culture conditions and signaling molecules. Cardiomyocytes, key cellular component of cardiac organoid, are responsible for the beating of the cardiac organoids. The progenitor cells display a regular, cardiac-like contraction. The beating rate of the formed cardiac organoids increases dramatically when stimulated with isoproterenol or forskolin, and there is a linear relationship between the concentration of the drug and the beating rate over a range of concentrations. The model is suitable for studying electrical signaling and compound effects. It therefore facilitates drug efficacy testing and safety assessment with high responsiveness.

Literature: Drakhlis et al., Nat Biotechnol. 2021 Jun;39(6):737-746

Signal factors:

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human TGF-beta 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Cortical

Human brain organoids (“mini-brains”) consist of self-organized three-dimensional (3D) neural tissue which can be derived from reprogrammed adult cells and maintained for months in culture. These 3D structures manifest substantial potential for the modeling of neurodegenerative diseases and pave the way for personalized medicine. Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), also from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSCs) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials.

More recently,  human neural cells derived directly from patients with diverse neurological diseases is possible. However, the potential of hiPSCs to recapitulate complex human brain disorders remains incompletely exploited.

Literature: Jacob et al., Cell Stem Cell. 2020 Dec 3;27(6):937-950

Signal factors:

human BDNF

human FGF-8/8b

human FGF-8a

human GDNF

human TGF-beta 1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Esophagus

In recent years, esophageal organoids derived from multiple cell sources have been established, and relatively mature culture protocols have been developed. Esophageal inflammation and cancer are two directions of esophageal organoid modeling, and organoid models of esophageal adenocarcinoma and esophageal squamous cell carcinoma, have been established.Pluripotent stem cells (PSCs) could provide a powerful system to model development of the human esophagus, whose distinct tissue organization compared to rodent esophagus suggests that developmental mechanisms may not be conserved between these species.Multiple signaling pathways such as WNT and BMP have been shown to play essential roles in the development of different organs including the lung and esophagus.

Inhibition of TGF-ß and BMP signaling is required for sequential specification esophageal progenitor cells (EPCs) from human PSCs.The hPSC-derived EPCs express genes that are enriched in the human fetal esophagus, and they are able to recapitulate human esophageal developmental processes.  The properties of esophageal organoids, which mimic the real esophagus, contribute to research in drug screening and regenerative medicine.

Literature: Zhang et al., Cell Stem Cell. 2018 Oct 4;23(4):516-529

Signal factors:

human Activin A

human BMP-4

human EGF

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human FGF-10

human FGF-7/KGF

human Noggin

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Intestine

The small intestine is a major organ that regulates digestive function and nutrient absorption.The study of human intestinal growth and development in healthy and diseased conditions has always been challenging. The development of three-dimensional organoid cultures has transformed this entirely. Intestinal organoids are self-organized three-dimensional structures that partially recapitulate the identity, cell heterogeneity and cell behaviour of the original tissue in vitro. Therefore, over the past decade, the use of human organoid cultures has been instrumental to model human intestinal development, homeostasis, disease, and regeneration. Intestinal organoids can be derived from induced pluripotent stem cells (iPSC) or from adult somatic intestinal stem cells (ISC). Both types of organoid sources harbour their respective strengths and weaknesses. While human intestinal organoids were the first human organoid types that were successfully established in vitro, many protocols have since been optimized for organoids of many other tissue types, including pancreas, liver, kidney, stomach and lung.

Literature: McCracken et al., Nat Protoc. 2011 Nov 10;6(12):1920-8

Signal factors:

human Activin A

human EGF

human FGF-4

human Noggin

human R-Spondin 1

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Kidney

In the last decade, human pluripotent stem cell (hPSCs) differentiation methodologies have amazingly progressed toward the generation of three-dimensional (3D) tissue-like structures, Kidney organoids generated from iPSC have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Developmental mechanism were identified which are regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, it was possible to generate kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and vasular endothelial cells. However, Although the hPSC organoid field is rapidly growing, yet several challenges remain to be solved. These limitations include, among others, high variability in terms of differentiation extent and functional properties between organoids. Kidney organoids for studying human kidney development are very valuable in vitro models for drug screening and disease modeling, to mention only a few examples.

Literature: Takasato et al., Nature. 2015 Oct 22;526(7574):564-8

Signal factors:

human FGF-9

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Liver

The liver is one oft the largest internal organ in the human body and is involved in a wide variety of processes including synthesis of many plasma proteins. More recently a reliable and reproducible protocol was introduced to generate human liver organoids in 3-4 weeks derived from pluripotent stem cells (PSCs). These organoids are intra-luminally polarized to form canalicular structures and are comprised of mainly hepatic epithelial cells, co-differentiated with stellate-like and hepatic macrophage-like cells and other supportive cells that enables hepatic inflammatory disease modeling in vitro. These multi-lineage liver organoids express hepatocyte genes, secrete albumin and have vital metabolic functions. This approach utilizes PSC derived 3D human liver organoids as a renewable, reproducible and personalized cell source, thus facilitating disease modelling, mechanistical studies as well as drug screening with a future goal of developing novel therapeutics against currently intractable diseases.

Literature: Ramli et al., Gastroenterology 2020 Oct;159(4):1471-1486

Signal factors:

human Activin A

human BMP-4

human EGF

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human FGF-7/KGF

human FGF-19

human HGF

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Lung

The lung epithelium is derived from the endodermal germ layer, which undergoes a complex series of endoderm-mesoderm-mediated signaling events to generate the final arborized network of conducting airways and gas-exchanging units. Recent approaches describe human lung organoids possess cell types and structures that resemble the bronchi/bronchioles of the developing human airway surrounded by lung mesenchyme and cells expressing alveolar-cell markers. The bud tip progenitor organoids possess a population of highly proliferative multipotent cells with in vitro multilineage differentiation potential and in vivo engraftment potential. Starting with hPSCs lung organoids can be generated in about 2-3 months,  bud tip progenitor organoids can be generated in about 3 weeks in culture. The   lung organoids can be used to model epithelial-mesenchymal cross-talk during human lung development. Furthermore, the development of expandable organoids grown from stem cells or patient tissue samples provides a method for high-throughput screening of drugs and the potential uses for translational and personalized medicine.

Literature: Dye et al., elife 2016 Sep 28:5:e19732.

Signal factors:

human Activin A

human FGF-4

human FGF-10

human Noggin

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Mammary

Currently, the 3D breast organoid is the state-of-the-art model in human mammary gland research, utilizing induced pluripotent stem cells (iPSCs) or processed patient-derived breast tissues embedded in a special extracellular matrix that are then able to grow into complex structures that recapitulate aspects of native human breast. The human mammary gland is the major organ involved in lactation. In the mammary gland, alveoli secrete milk and myoepithelial cells contract to propel the milk through branched structures called ducts and eventually to the nipple. It is through this process of lactation that infants receive milk, which is essential for proper infant growth and development. Gaining more biological insight into the process of lactation through these breast tissue-mimetic 3D models is essential for further studies on lactation-associated human mammary gland diseases as well as human milk composition, and potential solutions to challenges in maternal milk accessibility. The currents findings provide an iPSC-based model for studying regulation of normal mammary cell fate and function as well as breast disease development.

Literature: Qu et al., Stem Cell Reports 2017 Feb 14;8(2):205-215

Signal factors:

human FGF-10

human HGF

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Pancreas

Pluripotent stem cells-derived pancreatic progenitors form pancreatic organoids that comprise acinar/ductal-like progeny and resemble human pancreas upon orthotopic transplantation in mice. The term organoid refers to a group of cells growing in a 3D structure that is generated directly from primary tissues, embryonic stem cells, or pluripotent bridge between in vitro and in vivo models.vivo at least until a fetal developmental stage. Diabetes and pancreatic ductal adenocarcinoma (PDAC) are the two major devastating diseases affecting the pancreas.  Suitable models for regenerative medicine in diabetes and to pancreatic commitment in vitro and in accurately study PDAC biology and treatment response are essential in the pancreatic field. Pancreatic organoids can be generated from healthy pancreas or pancreatic tumors and constitute stem cells, with self-renewal and self-organization capacity, maintaining similar appearance and functionality as the original tissue. Induced PSCs from cystic fibrosis patients display normal and important translational steps towards disease development.

Literature: Koike et al., Nat Protoc  2021 Feb;16(2):919-936

Signal factors:

human Activin A

human BMP-4

human FGF-4

human Noggin

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Retina

The retina, an integral part of the central nervous system (CNS), consists of seven different cell types, histologically organized in an evolutionarily conserved laminar structure, which are responsible for generating and transmitting the visual signals from the eyes. For example, rod and cone photoreceptors (rods and cones, respectively) capture light reflected from an object and generate an electrical signal. The loss of the visual signal when photoreceptors degenerate in age-related macular degeneration (AMD) or retinitis pigmentosa (RP) or the lost ability to transmit it to the brain when retinal ganglion cells (RGCs) degenerate in glaucoma invariably leads to blindness. Intensive research over the last twenty years has led to discoveries that are promising for regenerative medicine: self-organization of pluripotent stem cells into 3D retinal organoids, providing platforms for disease modelling and cells for retinal repair. When combined with drug screening and disease modelling using iPSC lines from patients have the potential for new clinical trials and furthermore, to select patients for personalized treatment.

Literature: Regent et al., Mol Vis 2020 Mar 3:26:97-105

Signal factors:

human IGF-1

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Skin

The skin, being the body’s largest organ, performs a range of functions, including protection, sensation, and thermoregulation. It comprises three layers enclosed by a membrane: the epidermis, dermis, and hypodermis. Some advances have been made in recent years in the development of highly sophisticated skin organoids. Serving as three-dimensional models that mimic human skin. Organoids can evolved into complex structures and are increasingly recognized as effective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional systems and ethical concerns. More recently, the construction of an almost complete in vitro self-organized skin system has been reported differentiated from iPSCs, forming a hierarchical skin organoid that recapitulated many appendage structures, including hair follicles. Almost simultaneously, organoids containing sebaceous or sweat glands derived from reprogrammed epithelial tissue cells were developed.

Literature: Lee et al., Nature 2020 Jun;582(7812):399-404.

Signal factors:

human FGF-2/bFGF (153 aa)

human FGF-2/bFGF (146 aa)

human BMP-4

If you need larger quantities of a molecule, just ask us.
Click here for our contact details

We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.

Stomach

Over the past several decades, developmental biologists have discovered fundamental mechanisms by which organs form in developing embryos. With this information it is now possible to generate human "organoids" by the stepwise differentiation of human pluripotent stem cells using a process that recapitulates organ development. The stomach derives from the posterior foregut and retinoic acid signaling is required for promoting a posterior foregut fate. The small and large intestine derive from the mid and hindgut, respectively. These stages of gastrointestinal development can be precisely manipulated through the temporal activation and repression of the pathways.  For example, SOX2-expressing foregut spheroids can be further patterned into posterior foregut by addition of retinoic acid. Once formed, these posterior foregut spheroids can be grown in three-dimensional human gastric organoids that have all of the cell types of antral part of the stomach.  In further studies, the resulting gastric organoids were composed of epithelial glands surrounded by multiple layers of functionally innervated smooth muscle. The technology can readily transferrable to other types of organoids and used to engineer esophageal organoids containing all 3 germ layers. The tractability of this approach allows to study germ layer communication during stomach development.

Literature: McCracken et al., Nature  2014 Dec 18;516(7531):400-4

Signal factors:

human Activin A

human EGF

human FGF-4

human Noggin

human Wnt-3a

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We have even more cytokines and growth factors. We also have soluble receptors and a variety of monoclonal and polyclonal antibodies to discover.