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Method Article
Islet-like cells derived from ductal cells demonstrate potential for the treatment of diabetes by lowering blood glucose levels and enhancing insulin production in diabetic rats. Nevertheless, challenges remain in ensuring sufficient cell function, immunological defense, and safety. Additional investigation is required to enhance the therapeutic capacity of these substances.
The use of islet-like cells derived from ductal cells has emerged as a potential approach for treating type 1 diabetes. Diabetic patients have insufficient insulin synthesis in their bodies due to the autoimmune destruction of pancreatic beta cells responsible for making insulin. Within this framework, the objective of islet cell transplantation is to reinstate the ability of patients to produce insulin. However, obstacles such as the insufficient acquisition of islet cells from donor pancreases and immune reactions hinder the broad application of this therapy method. Under specific circumstances, pancreatic ductal cells possess the capability to transform into cells that produce insulin. These cells could be cultivated in a controlled environment and converted into islet-like cells that have the capability to release insulin, making them suitable for transplantation. This innovative strategy offers the potential to halt the progression of type 1 diabetes and reduce dependence on insulin injections. In this study, islet-like cells derived from ductal cells were transplanted into the liver through the portal vein of the liver in streptozotocin-induced diabetic rats. Following transplantation, we noted substantial reductions in the rats' blood glucose levels starting on day 5, which continued for 15 days. In addition, an intraperitoneal glucose tolerance test (IPGTT) demonstrated that diabetic rats receiving the islet-like cell transplants produced significantly more insulin than the control group. These results suggest that islet-like cells derived from ductal cells may be a promising therapeutic approach for diabetes. The primary obstacles in this field of study include achieving sufficient functional capability for the cells, shielding them from the immune system, and ensuring their safety for therapeutic application. Future studies endeavors have the potential to yield crucial insights for optimizing the use of these cells in therapeutic settings, with a focus on enhancing both efficacy and safety.
Type 1 diabetes is a persistent autoimmune disorder marked by the destruction of beta cells in the pancreas that produce insulin. The current treatments mostly include long-term insulin therapy, which, although successful in controlling blood glucose levels, does not provide a cure for the condition or halt its advancement1. The investigation of alternative therapies for Type 1 diabetes is motivated by the necessity for more efficacious alternatives than the existing emphasis on insulin treatment. Ongoing research has been prompted by this, focusing on alternate treatments such as islet cell transplantation, which seeks to reinstate the body....
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This study adhered to the ARRIVE recommendations, ensuring that the design, execution, and reporting of the research met high standards for animal welfare and experimental integrity (https://arriveguidelines.org). Ankara Medipol University secured approval from the ethics committee (AMUHADYEK-12- 09.05.2025) and institutional authorization. All methods were performed in compliance with applicable guidelines and regulations. All measures were enacted to minimize animal suffering and to employ the minimum number of animals necessary to achieve scientific objectives.
1. Preparation of solutions
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Light microscopy analysis
During the 14th day examinations of ductal cells, light microscopy analysis revealed that the cells clustered and formed an islet-like structure. This structural change indicates that after a certain period, ductal cells change their morphological characteristics by entering an organizational order and gaining an islet-like appearance. The tendency of the cells to cluster is probably due to the effects of intercellular communication and the.......
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The study of the functional capacity of islet-like cells from different sources has attracted considerable interest in diabetes research. Initial research shows that these cells can release insulin when glucose levels are raised, which suggests that they might be able to mimic the functions of natural pancreatic islets. Researchers have utilized dithizone staining to verify the phenotypic resemblance of islet-like cells to pancreatic islets, as evidenced by the characteristic red staining present in these cells
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No potential conflict of interest was reported by the author(s).
The authors would like to thank the laboratory team for their contributions to the study.
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| Name | Company | Catalog Number | Comments |
|---|---|---|---|
| 0.9% Sodium Chloride | Sahar Pharma | For removal of pancreas and cell transplantation | |
| 10 mL serological pipette - sterile | Corning | 4488 | For isolation |
| 24 well plate | Corning | 353047 | For GSIS |
| 25 mL serological pipette - sterile | Corning | 4489 | For isolation |
| 70% ethanol | ISOLAB | 64-17-5 | For desinfection of rats |
| betadine | Baticonol | 1186 | For desinfection of rats |
| Biocholl 1077 | Sigma | L6715-BC | For pancreas purification |
| Biocoll, Density 1.10 g/mL | Sigma | L6155-BC | For pancreas purification |
| Blood glucose meters and glucose test strips | On Call Plus | For measuring blood glucose | |
| BSA | Sigma | A9418 | For preperation of krebs |
| CaCl2 | Sigma | 57647902 | For preperation of krebs |
| Catheter composition: Polyethylene catheter (intravenous intracath) | Bicakcilar | 24G and 14G | For pancreas and liver |
| Centrifuge | Thermo | ST1R Plus | For isolation |
| Collagenase Type V, ≥ 1 FALGPA units/mg solid, >125 CDU/mg solid | Sigma | C9263- 1G | For pancreas digestion |
| D-(+)-glucose | Sigma | 50-99-7 | For GSIS and IPGTT |
| Dithizone (DTZ) | Sigma | D5130 | For islet determination |
| DMSO | Sigma | D8779 | For solve to DTZ |
| Dulbecco’s Modified Eagle’s Medium (DMEM—low glucose) | Gibco | 11885084 | For cell culture |
| Eppendorf tube | ISOLAB | For cell washing | |
| Falcon tube (50 mL) | ISOLAB | LB.IS.078.02.009 | For isolation |
| fetal bovine serum (FBS) | Sigma | N4637 | For pancreas isolation and culture |
| Fine needle and suture material (size 6-0 or 7-0) | PROLENE Blue 18" | P-1 Needle | 8697G | For removal of pancreas and cell transplantation |
| glucagon-like peptide 1 (GLP-1) | Aladdin | rp174144 | For Cell Culture |
| Hank's balanced salt solution (HBSS with Ca-Mg) | Capricorn | HBSS-1A | For enzyme preperation |
| HBSS no calcium, no magnesium, no phenol red | BIOCHROM | L2015 | For pancreas isolation |
| HEPES | Lonza | For cell culture | |
| Insulin Elisa | Alpco | 80-INSRT-E01 | For insulin elisa |
| insulin-transferrin-selenium (ITS) | Gibco | ITS -G | For cell culture |
| Isoxazole 9 (ISX-9) | Aladdin | I304735-10mg | For cell culture |
| KCl | Sigma | 329820207 | For preperation of krebs |
| Ketamine HCl 200 mg/mL | NexGen | For rats anestesia | |
| Laminar Flow Cabinets | Labor Ildam | BSC-1100IIA2-X | For isolation and Culture period |
| Lancets | Ayset | 28 G | For measuring blood glucose |
| L-glutamine | Sigma | 59202c | For pancreas isolation and culture |
| MgCl2 | Sigma | 329759772 | For preperation of krebs |
| microplate reader | BioTek Synergy | H1 Multimode Reader | For insulin elisa |
| microplate shaker | VWR | 444-0270 | For insulin elisa |
| Microsurgical microscope | EMZ- | 200TR 3.9X | For removal of pancreas and cell transplantation |
| Microsurgical scissors and forceps | Aesculap | For removal of pancreas and cell transplantation | |
| Millicell Hanging Cell Culture Insert, polyethylene terephthalate 8.0µm | MILLIPORE | PIEP30R48 | For GSIS |
| NaCl | Sigma | 7647-14-5 | For preperation of krebs |
| NaHCO3 | Sigma | 144-55-8 | For preperation of krebs |
| Pasteur Pipette 3 Ml | BIOSIGMA | For isolation | |
| penicillin/streptomycin | Sigma | For pancreas isolation and culture | |
| Phosphate buffered saline solution (PBS) | BIOCHROM | L1815 | For cell passaging |
| Retractor (for the stabilization of the liver and connective tissues) | Aesculap | For removal of pancreas and cell transplantation | |
| Roswell Park Memorial Institute Medium (RPMI w/L-Gln) | Capricorn | RPMI-A | For pancreas isolation and culture |
| Steril Cotton Tipped | Dynarex | For removal of pancreas and cell transplantation | |
| Sterile syringe (10 mL) | Ayset | 32MM 22G | For Collegenase reaction |
| Stopwatch | Kenko | KK613D | For IPGTT |
| Streptozotocin (STZ) | Sigma | 18883-66-4 | For occur diabetic rats |
| Syringe Driver Filter Unit (GP-0.22 µm-3 mm) | Millex | SLGP033RS | For sterilisation of cell culture media |
| T25 flask | Thermo | 130189 | For culture |
| TrypLE Express reagents | Gibco | For cell passaging | |
| water bath | Labor Ildam | ALB128 | For collegenase reaction |
| Xylazine 2% w/v Solution for Injection | Rompun | For rats anesthesia |
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