Transforming growth factor-β1/Thrombospondin-1/CD47 axis mediates dysfunction in CD34 cells derived from diabetic older adults.

Aging with diabetes is associated with impaired vasoprotective functions and decreased nitric oxide (NO) generation in CD34 cells. Transforming growth factor- β1 (TGF-β1) is known to regulate hematopoietic functions. This study tested the hypothesis that transforming growth factor- β1 (TGF-β1) is upregulated in diabetic CD34 cells and impairs NO generation via thrombospondin-1 (TSP-1)/CD47/NO pathway.

Reversal of Bone Marrow Mobilopathy and Enhanced Vascular Repair by Angiotensin-(1-7) in Diabetes.

The angiotensin (ANG)-(1-7)/Mas receptor (MasR) pathway activates vascular repair-relevant functions of bone marrow progenitor cells. We tested the effects of ANG-(1-7) on mobilization and vasoreparative functions of progenitor cells that are impaired in diabetes. The study was performed in streptozotocin-induced diabetic (db/db) mice.

Enhancing the function of CD34(+) cells by targeting plasminogen activator inhibitor-1.

Previously, we showed that transient inhibition of TGF- β1 resulted in correction of key aspects of diabetes-induced CD34(+) cell dysfunction. In this report, we examine the effect of transient inhibition of plasminogen activator inhibitor-1 (PAI-1), a major gene target of TGF-β1 activation. Using gene array studies, we examined CD34(+) cells isolated from a cohort of longstanding diabetic individuals, free of microvascular complications despite suboptimal glycemic control, and found that the cells exhibited reduced transcripts of both TGF-β1 and PAI-1 compared to age, sex, and degree of glycemic control-matched diabetic individuals with microvascular complications.

Transient inhibition of transforming growth factor-beta1 in human diabetic CD34+ cells enhances vascular reparative functions.

Objective: Peripheral blood CD34(+) cells from diabetic patients demonstrate reduced vascular reparative function due to decreased proliferation and diminished migratory prowess, largely resulting from decreased nitric oxide (NO) bioavailability. The level of TGF-beta, a key factor that modulates stem cell quiescence, is increased in the serum of type 2 diabetic patients. We asked whether transient TGF-beta1 inhibition in CD34(+) cells would improve their reparative ability.

Autocrine transforming growth factor-beta regulation of hematopoiesis: many outcomes that depend on the context.

Transforming growth factor-beta (TGF-beta) is a pleiotropic regulator of all stages of hematopoieis. The three mammalian isoforms (TGF-beta1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Depending on the differentiation stage of the target cell, the local environment and the concentration and isoform of TGF-beta, in vivo or in vitro, TGF-beta can be pro- or antiproliferative, pro- or antiapoptotic, pro- or antidifferentiative and can inhibit or increase terminally differentiated cell function.

Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts.

The mammalian heart has a very limited regenerative capacity and, hence, heals by scar formation. Recent reports suggest that haematopoietic stem cells can transdifferentiate into unexpected phenotypes such as skeletal muscle, hepatocytes, epithelial cells, neurons, endothelial cells and cardiomyocytes, in response to tissue injury or placement in a new environment. Furthermore, transplanted human hearts contain myocytes derived from extra-cardiac progenitor cells, which may have originated from bone marrow.