Emerging Roles for Mesencephalic Astrocyte-Derived

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Conclusion and Prospects for MANF as Regenerative Therapeutic Agent in Diabetes
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The data discussed in this review suggest that MANF is a novel potent beta cell protective and mitogenic factor for human and mice beta cells. The mechanism of action for MANF is still elusive but point to a regenerative effect acting both intracellularly and exogenously through modulating sustained ER stress in beta cells, which is an important factor contributing to beta cell dysfunction and death leading to insulin-deficiency in T1D and T2D. Thus MANF alone or in combination with other drugs is a potential agent for development into a regenerative drug for beta cells in diabetes. From the translational and clinical point of view, results with mice suggest that MANF could be delivered to diabetic human pancreas and beta cells through viral AAV vectors by endoscopic non-surgical procedures. However, clinical trials using AVV vectors will uncover whether the use of these vectors are efficient and safe. Future studies will reveal whether MANF protein-based systemic delivery can normalize blood glucose levels in rodent models of diabetes. In addition, efforts to improve MANF stability and efficacy will be required for translating the MANF therapy to humans.

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