From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges
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From Mesenchymal Stromal/Stem Cells to Insulin-Producing Cells: Progress and Challenges Mohamed A. Ghoneim 1
&
Ayman F. Refaie 1 & Batoul L. Elbassiouny 1 & Mahmoud M. Gabr 1 & Mahmoud M. Zakaria 1
# The Author(s) 2020
Abstract Mesenchymal stromal cells (MSCs) are an attractive option for cell therapy for type 1 diabetes mellitus (DM). These cells can be obtained from many sources, but bone marrow and adipose tissue are the most studied. MSCs have distinct advantages since they are nonteratogenic, nonimmunogenic and have immunomodulatory functions. Insulin-producing cells (IPCs) can be generated from MSCs by gene transfection, gene editing or directed differentiation. For directed differentiation, MSCs are usually cultured in a glucose-rich medium with various growth and activation factors. The resulting IPCs can control chemically-induced diabetes in immune-deficient mice. These findings are comparable to those obtained from pluripotent cells. PD-L1 and PD-L2 expression by MSCs is upregulated under inflammatory conditions. Immunomodulation occurs due to the interaction between these ligands and PD-1 receptors on T lymphocytes. If this function is maintained after differentiation, life-long immunosuppression or encapsulation could be avoided. In the clinical setting, two sites can be used for transplantation of IPCs: the subcutaneous tissue and the omentum. A 2-stage procedure is required for the former and a laparoscopic procedure for the latter. For either site, cells should be transplanted within a scaffold, preferably one from fibrin. Several questions remain unanswered. Will the transplanted cells be affected by the antibodies involved in the pathogenesis of type 1 DM? What is the functional longevity of these cells following their transplantation? These issues have to be addressed before clinical translation is attempted. Keywords MSCs . differentiation . IPCs . transplantation . encapsulation . scaffolds . immunomodulation . diabetes
Introduction Diabetes mellitus (DM) is a major health concern. In 2014, more than 400 million people suffered from DM globally compared to 108 million in 1980. If this trend continues, the number is expected to increase to more than 600 million by 2045 [1]. Type 1 DM (T1DM) accounts for ≈5% of all diabetic patients and is the result of destruction of pancreatic islets through an autoimmune-mediated response. Patients depend on exogenous insulin injections throughout their life. However, this treatment does not prevent acute or chronic complications. Glycemic control without a need for exogenous insulin can be achieved by β-cell replacement through transplantation of the whole pancreas or its islets. Despite the increasing success of both approaches, their applications are
* Mohamed A. Ghoneim [email protected] 1
Urology and Nephrology Center, Mansoura, Egypt
limited by organ availability and the need for life-long immunosuppression. Recent progress in the field of regenerative therapies provides an alternative means through the generation of surrogate β-cells from vari
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