Research Topic

Alternative Regenerative Medicine for Diabetes: beyond the stem cell approach

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The alternative regenerative medicine approach is to explore the post-embryonic regeneration of tissues like the pancreas, as a therapeutic application option for a variety of diseases. Post-embryonic regeneration of tissues applies to the liver, kidney, peripheral tissues (i.e. wound healing), and ...

The alternative regenerative medicine approach is to explore the post-embryonic regeneration of tissues like the pancreas, as a therapeutic application option for a variety of diseases. Post-embryonic regeneration of tissues applies to the liver, kidney, peripheral tissues (i.e. wound healing), and others.

We created a novel biologic approach that integrates multiple levels of cellular physiology to regulate organ regenerative capacity through post-embryonic mechanism. We named this new field of research “Cellular Networking Integration & Processing (CNIP)”. Most research programs today focus on a reductionist approach: one molecule for one cellular physiological condition.

The fundamental principle underlying CNIP is to simultaneously target and integrate three key levels of metabolic and cellular control: (1) glucose metabolism; (2) activation of tyrosine kinase receptors; (3) gene expression that has been implicated in beta cell formation in vivo. Glycolysis is the first important element in our CNIP approach to induce beta-cell formation in the adult pancreas. Therefore, the first molecule included in our CNIP cocktail to generate pancreatic beta cell formation is glucokinase. A second cellular function involved in beta cell formation is ligand binding to tyrosine kinase receptors. Protein-tyrosine phosphatase 1B (PTP1B) has been shown to inhibit the ability of insulin, insulin-like growth factor, prolactin and hepatocyte growth factor to activate tyrosine kinase receptors which play an important regulator role in beta cell regeneration. Consequently, the second molecule included in our CNIP cocktail to generate insulin-producing beta cells formation is a shRNA, which targets PTP1B and increases receptor tyrosine kinases activity. The third important step in our CNIP approach is focused at the gene expression level and utilizes the transcriptional factor, Pdx-1, which functions as an attractor to converge, integrate, and direct glucose metabolism and tyrosine kinase receptor(s) activity to form new beta-cells in the adult pancreas. Pdx-1 is a key transcription factor associated with beta-cell formation in the adult pancreas. The lentivirus construct expressing the cDNA of glucokinase, Pdx-1 and shRNA PTP1B was injected into the pancreatic duct via a catheter in the partially pancreatectomized mouse model of diabetes and demonstrated that CNIP induced pancreatic beta cell formation in vivo in adult animals and normalized fasting and post prandial blood glucose and plasma insulin concentration without hypoglycemia (Doiron et al., 2016 Curr. Pharm Biotechnol 17: 376-388). The CNIP approach can be applied to the treatment of cancer, wound healing, and many other medical diseases with modifications based on the specific disease.

In summary, the CNIP method provides a novel approach to regenerate beta cells using the natural physiologic cellular capacity of adult cells in the pancreas in vivo and can be used for prevention, treatment, or cure for both type 1 and type 2 diabetes with the understanding that, in type 2 diabetes, treatment of the insulin resistance will require a separate approach. For treatment of diabetic individuals who are not intrinsically insulin resistant, the CNIP approach provides a potential cure.

The CNIP approach, which targets the post-embryonic regenerative capacity of tissues, represents an alternative approach in regenerative medicine and is the focus of this Frontier topic. Additionally, we welcome any innovative approach, and basic research targets in vivo cellular mechanism at the post-embryonic developmental level and which provides a novel therapeutic application in regenerative medicine.

Topic Editors:
Bruno Doiron, Ph.D.
Assistant Professor
Department of Medicine – Diabetes Division
University of Texas Health Center at San Antonio, USA

Ralph Anthony DeFronzo, MD
Professor of Medicine
Chief, Diabetes Division
University of Texas Health Center at San Antonio, USA
and
Deputy Director
Texas Diabetes Institute
San Antonio Texas, USA


Keywords: regenerative medicine, beta cells, synergic, systems biology


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