Human iPSC-Derived Beta Cells

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Cat.No.

CSC-00888L

Description

Human iPSC-Derived Beta Cells have been differentiated from our control human induced pluripotent stem (hiPS) cells, dissociated into a single-cell suspension, and frozen in vials. These cells secrete high amounts of insulin and C-peptide, and they show substantial protein expression of insulin/C-peptide, MAFA, NKX6-1, PDX1, and UCN3. Human iPSC-Derived Beta Cells are ideal for investigating beta cell function, diabetes/disease modeling, and compound screening for insulin secretion and regulation.

Species

Human

Application

For Research Use Only

Storage and Shipping

Directly and immediately transfer cells from dry ice to liquid nitrogen upon receiving and keep the cells in liquid nitrogen until cell culture needed for experiments.

Citation Guidance

If you use this products in your scientific publication, it should be cited in the publication as: Creative Bioarray cat no. If your paper has been published, please click here to submit the PubMed ID of your paper to get a coupon.

Pancreatic beta cells are the sole source of insulin, and their dysfunction or destruction underlies diabetes mellitus. Primary human beta cells are notoriously scarce, fragile, and refractory to expansion in vitro, severely limiting their use for mechanistic studies, drug discovery, and cell replacement therapy. The advent of human induced pluripotent stem cell (iPSC) technology has revolutionized the field by enabling the directed differentiation of patient-specific or healthy donor-derived iPSCs into functional insulin-producing beta cells.

Key advantages of human iPSC-derived beta cells over primary counterparts include: (1) unlimited scalability - iPSCs can be expanded indefinitely and differentiated in large batches, ensuring consistent and reproducible cell supply; (2) patient-specific modeling - iPSCs derived from individuals with monogenic or polygenic diabetes enable personalized disease modeling and drug testing; (3) genome-editing compatibility - CRISPR/Cas9 correction or introduction of disease-associated mutations allows causal gene-function studies; (4) avoidance of ethical concerns associated with fetal or cadaveric tissue; and (5) potential for cell replacement therapy - encapsulated or immunoprotected iPSC-derived beta cells are being evaluated for diabetes treatment.

Collectively, human iPSC-derived beta cells provide a powerful, renewable, and physiologically relevant in vitro platform for studying beta cell biology, diabetes pathogenesis, and for high-throughput screening of insulin secretagogues or cytoprotective agents.

In Depth Functional Characterization of Human Induced Pluripotent Stem Cell-Derived Beta Cells In Vitro and In Vivo

In vitro differentiation of human induced pluripotent stem cells (iPSCs) into beta cells represents an important cell source for diabetes research. Here, we fully characterized iPSC-derived beta cell function in vitro and in vivo in humanized mice. Using a 7-stage protocol, human iPSCs were differentiated into islet-like aggregates with a yield of insulin-positive beta cells comparable to that of human islets. The last three stages of differentiation were conducted with two different 3D culture systems, rotating suspension or static microwells. In the latter, homogeneously small-sized islet-like aggregates were obtained, while in rotating suspension size was heterogeneous and aggregates often clumped. In vitro function was assessed by glucose-stimulated insulin secretion, NAD(P)H and calcium fluctuations. Stage 7 aggregates slightly increased insulin release in response to glucose in vitro. Aggregates were transplanted under the kidney capsule of NOD-SCID mice to allow for further in vivo beta cell maturation. In transplanted mice, grafts showed glucose-responsiveness and maintained normoglycemia after streptozotocin injection. In situ kidney perfusion assays showed modulation of human insulin secretion in response to different secretagogues. In conclusion, iPSCs differentiated with equal efficiency into beta cells in microwells compared to rotating suspension, but the former had a higher experimental success rate. In vitro differentiation generated aggregates lacking fully mature beta cell function. In vivo, beta cells acquired the functional characteristics typical of human islets. With this technology, an unlimited supply of islet-like organoids can be generated from human iPSCs that will be instrumental to study beta cell biology and dysfunction in diabetes.

Human iPSC-derived beta cells have an immature functional phenotype in vitro. — Fig. 1. *In vitro* function of human iPSC-derived beta cells (Fantuzzi, Federica, *et al.*, 2022).

Human iPSC-derived beta cells acquire a mature functional phenotype in vivo. — Fig. 2. *In vivo* function of human iPSC-derived beta cells (Fantuzzi, Federica, *et al.*, 2022).

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For research use only. Not for any other purpose.