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Linagliptin Improves CD34+ Stem Cell Function in Patients with Type II Diabetes and Chronic Kidney Disease

Oct 13, 2020 10:06:00 AM / by Stacy Matthews Branch, DVM, PhD

Close up of lab assistant in uniform, with mask and rubber gloves holding test tube with blood sample while sitting on chair and typing on laptop. Selective focus on test tubes_AdobeStock_305409092-2-1According to BMC, after a study was conducted with patients that had Type II Diabetes and Chronic Kidney Disease, researchers found the Linagliptin improved CD34+ve Endothelial Progenitor Cells.

Type II diabetes mellitus (DM) is a chronic disorder characterized by an impaired response to insulin production. There is a significant impairment of the endothelium in DM, and this endothelial dysfunction is a fundamental change that leads to cardiovascular disease progression. Endothelial dysfunction also plays an important role in the effects on neovascularization and impaired wound healing.

The mechanism of endothelial dysfunction seen in DM and chronic kidney disease (CKD) is linked to altered function of CD34+ stem cells (endothelial progenitor cells). Dysfunction of the progenitor cells leads to deficient regeneration of the endothelium and poor renal perfusion. Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used DM treatments that may increase SDF1 alpha bioavailability, a group of chemokines that regulate various cell types, including CD34+ stem cells. 

DPP4 inhibitors may direct CD34+ stem cells to areas of endothelial damage for regeneration to take place. Therefore, adding DPP4 inhibitors to other DM treatments, including metformin and insulin, may address the endothelial dysfunction seen in patients with DM and CKD. To this end, researchers conducted a placebo-controlled clinical trial to study the effects of linagliptin added to metformin and/or insulin in patients with both type II diabetes and chronic kidney disease. 

The study results show that CD34+ stem cell numbers and migratory function increased in patients treated with linagliptin. Arterial stiffness measures, pulse wave velocity and pulse wave analysis, were improved, and a reduction in LDL: HDL ratio was observed in the patients treated with linagliptin. Also noted was a trend toward enhancing urinary exosome protein levels measured as a biomarker of kidney disease. Overall, linagliptin added to treatments for DM in patients with CKD led to improved CD34+ stem cell function and may prevent endothelial dysfunction. Further, CD34+ cells may serve as a biomarker to assess endothelial function and determine cardiovascular disease risk in patients with DM. 

For years, HemaCare has provided researchers with CD34+ stem cells so they can further advance their discovery. 


Awal, H., Nandula, S., Domingues, C., Dore, F., Kundu, N., & Brichacek, B. et al. (2020). Linagliptin, when compared to placebo, improves CD34+ve endothelial progenitor cells in type 2 diabetes subjects with chronic kidney disease taking metformin and/or insulin: a randomized controlled trial. Cardiovascular Diabetology, 19(1). doi: 10.1186/s12933-020-01046-z

Topics: Stem Cells

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