Pancreatic Islet Cells Culture As An Answer To Cell Therapy For Diabetes

Pancreatic Islet Cells Culture As An Answer To Cell Therapy For Diabetes

According to the International Diabetes Federation (http://www.idf.org/), more than 380 million people across the globe are affected by diabetes mellitus. The global expenditure due to the diseases was USD 612 billion in 2014. Around 1.6 million deaths were due to this condition according to the World Health Organization (WHO). The condition causes several complications according to the WHO ranging from kidney failure, increased risk of heart attacks and strokes (around two-fold) and neuropathy (nerve damage) that has a risk of limb amputation. 2.6% of blindness across the world is due to diabetic retinopathy.

10% of the patients show what is termed as type 1 diabetes (T1D) that involves an autoimmune condition with the immune system targeting the β-cells in pancreatic islet cells that produce insulin. The major section of patients shows type 2 diabetes (T2D) where there is a loss I function of the β-cells and insulin resistance in the tissues.

One approach to treat the disease is to transplant pancreatic islet cells into patients that hold the promise to overcome the daily insulin injections according to research published by Hao and team (2006) in Nature Medicine. The transplantation of islets can cause relief from using insulin over the long term as shown by 2012-published research in the American Journal of Transplantation by scientists Bellin and team.

Yet there are challenges in using transplantation given the donor cell shortage; the number of islets required for the transplantation is 2-3 human donor organs for one recipient making the process challenging (Zhou et al, 2012). This brings in the possibility of using the in vitro generation of β-cells. Early work in Science by Gershengorn and team showed that Mesenchymal Stem Cells could form insulin-expressing islet-like cell aggregates.

A team led by Niu reported the culture of pig islets and their suitability to form insulin-secreting cells in the Journal of Diabetes Research in 2016. The cultured cells secreted 4- to 18-fold higher levels of insulin in medium containing high levels of glucose that medium with lower glucose levels; showing the potential of these cells in sensing and responding to glucose-one of the hallmarks of β-cells. Additionally, transcription factors specific for the pancreas such as Pdx1 were maintained over the long term. This shows the utility of swine pancreatic islets beta cells.

The challenge of donor shortage for islet transplantation can be addressed with the use of swine or pig islets. The use of these cells becomes even more relevant given that human islets are available only for 1 out of 333 patients with insulin-dependent diabetes mellitus (IDDM) (Yang et al, 2016).

The use of these swine beta cells has arrived and further research using these cells looks promising!

References:

https://www.who.int/news-room/fact-sheets/detail/diabetes

  1. Hao, B. Tyrberg, P. Itkin-Ansari, et al., “Beta-cell differentiation from nonendocrine epithelial cells of the adult human pancreas,” Nature Medicine, vol. 12, no. 3, pp. 310–316, 2006
  2. D. Bellin, F. B. Barton, A. Heitman, et al., “Potent induction immunotherapy promotes long-term insulin independence after islet transplantation in type 1 diabetes,” American Journal of Transplantation, vol. 12, no. 6, pp. 1576–1583, 2012.
  3. Zhou, D. L. Mack, J. K. Williams, et al., “Genetic modification of primate amniotic fluid-derived stem cells produces pancreatic progenitor cells in vitro,” Cells Tissues Organs, vol. 197, no. 4, pp. 269–282, 2013.
  4. C. Gershengorn, A. A. Hardikar, C. Wei, E. Ceras-Raaka, B. Marcus-Samuels, and B. M. Raaka, “Epithelial-to-mesenchymal transition generates proliferative human islet precursor cells,” Science, vol. 306, no. 5705, pp. 2261–2264, 2004.

Guoguang Niu, John P. McQuilling, Yu Zhou, Emmanuel C. Opara, Giuseppe Orlando, and Shay Soker. In Vitro Proliferation of Porcine Pancreatic Islet Cells for β-Cell Therapy Applications. Journal of Diabetes Research 2016;   Article ID 5807876; 8 pages.  https://doi.org/10.1155/2016/5807876

Yi Yang, Kepin Wang, Han Wu, et al. Genetically humanized pigs exclusively expressing human insulin are generated through custom endonuclease-mediated seamless engineering, Journal of Molecular Cell Biology 8(2):174–177, 2016.

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