Harnessing CXCL12 signaling to protect and preserve functional β-cell mass and for cell replacement in type 1 diabetes

Pharmacology & Therapeutics
David A AlagpulinsaMark C Poznansky

Abstract

Type 1 diabetes (T1D) is a complex multifactorial disease characterized by autoimmune destruction of insulin-producing pancreatic β cells. Our understanding of the pathogenic mechanisms and natural history of T1D has evolved significantly over the past two decades; we can efficiently predict high-risk individuals, early diagnose the disease and stage progression. Fortuitously, novel in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells have been developed. These advances provide a definitive roadmap to implement realistic preventive and β-cell replacement therapies in T1D. Immunoprotection and preservation of functional β-cell mass are a sine qua non for the success of these interventions. The chemokine, stromal cell-derived factor-1alpha, known as CXCL12-α, is an attractive therapeutic target molecule in this context. CXCL12-α signaling promotes β-cell development, survival and regeneration and can mediate local immunomodulation in the pancreatic islets. Interestingly, CXCL12-α is robustly expressed in maturing insulin-producing β cells and in adult β cells during periods of injury and regeneration. However, under normal physiological settings, CXCL12-α is repressed in term...Continue Reading

Citations

Feb 13, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·David A AlagpulinsaMark C Poznansky
Jul 4, 2020·Nature Reviews. Materials·C L StablerB G Keselowsky
Jan 9, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Raphael N AlolgaGaoxiang Ma
Jan 6, 2021·Tissue Engineering. Part B, Reviews·Rei KuwabaraPaul de Vos
Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C BrittonP Reeves
Dec 23, 2021·Journal of Cellular and Molecular Medicine·Xiang-Yu ChenJing-Na Lin

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Disease Therapy

In autoimmune diseases, the immune system responds and attacks self-antigens and damages or impairs the function of the tissues. The treatment for autoimmune diseases often involves immunosuppressive agents, but newer treatments are being investigated. Discover the latest research on autoimmune disease therapy here.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

Autoimmunity Reviews
Concetta Ferretti, Antonio La Cava
Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association
Maria CsobonyeiovaLubos Danisovic
Current Diabetes Reports
Bernd BaumannBernhard O Boehm
Cellular and Molecular Life Sciences : CMLS
Liana GhazarianAgnès Lehuen
British Medical Bulletin
S L Thrower, P J Bingley
© 2022 Meta ULC. All rights reserved