Following the successful discovery of a protocol to encapsulate insulin-producing cells derived from human dental pulp mesenchymal stem cells a year ago, this year’s exploratory episode of the development of stem cell-based diabetes mellitus therapy enters a new phase. The findings of the initial encapsulation concept in the previous year were used for encapsulation of insulin-producing cells derived from dog fat tissue. Dogs were chosen because naturally-occurred diabetes mellitus in dogs is very high. A survey conducted in 2012 in the UK, from 128,210 examined dogs, there was about 0.34% of the dog population diagnosed with Type I Diabetes Mellitus, and the male castrated dogs (sterilized by extraction of testicles) are the high-risk group. In translational research for drug development in humans, currently, many researchers choose to use dogs as animal models due to several considerations, including the pathophysiology of Type I Diabetes Mellitus in dogs is very similar to the incidence in humans. Moreover, among large animals such as diabetes models, the incidence in dogs is much higher than in pigs and non-human primates(NHP). Current translational research on the development of diabetes mellitus therapy rarely uses experimental animal induction models with various methods, such as surgery or chemicals, because in some cases, the induction process does not result in pancreatic islet damage, and long-term monitoring is difficult to observe the risk of post-therapy complications.
The challenge in this research is the effort to produce insulin-producing cells that can function optimally. The initial stage is definitive endodermal induction, where dog fat mesenchymal stem cells are induced by adding chemical molecules such as Activin A and Chir99021. In the next stage, definitive endodermal will be triggered to turn into pancreatic endodermal, a critical stage in the production of insulin-producing cells. Some of the molecules added at this stage are taurine, retinoic acid, FGF2, EGF, SB431542, nicotine, dorsomorphine, and DAPT. The final stage of the insulin-producing cell production process is the cell maturation stage, at this stage, several molecules such as nicotine, taurine, GLP1, NEAA, forskolin, LY294002, and SB431542 were added in the induction medium. The induction process takes about 13 days to produce insulin-producing cells out of mesenchymal stem cells from dog fat tissue that are effective and have a function equivalent to pancreatic beta cells, which can respond to rising blood sugar levels by secreting insulin.
After insulin-producing cells can be produced, the next stage is the encapsulation process. Encapsulation needs to be done on cell-based therapy in an effort to prevent unwanted side effects, such as the release of rudimentary cell populations that may still carry genes that can harm the body, as well as efforts to protect the transplanted material from rejection reactions by the body. The encapsulation process used in this research is to use double encapsulation with alginate as the main encapsulation and pluronicas a coating. In this study, special media was also developed to store insulin-producing cells that had been encapsulated so that they could defend themselves and their functions. The results show that with a special medium named VSCBIC-1 media, the insulin-producing cells that have been encapsulated can be stored for at least 27 days in an incubator without any loss of quality or function. This is the first finding in the world and is expected to be used as a first step for pre-clinical trials in large animal models in the development of stem cell-based diabetes mellitus therapy. Furthermore, the results of this study can be used directly in the field of veterinary medicine as an effort to treat diabetes mellitus in pets.
Author: Suryo Kuncorojakti, drh., M.Vet.
Summarized from journal:
Dang Le, Q., Rodprasert, W., Kuncorojakti, S. et al. In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells. Sci Rep12, 9127 (2022). https://doi.org/10.1038/s41598-022-13114-3
