Growth Factor Preconditioning Increases the Function of Diabetes-Impaired Mesenchymal Stem Cells

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) possess multilineage differentiation potential and can be used for the treatment of diabetic heart failure. However, hyperglycemia can affect the function of MSCs adversely and merits the requirement for a strategy to correct this anomaly. MSCs were isolated from the tibias and femurs of C57BL/6 wild-type mice at 60 days after induction of diabetes by streptozotocin. MSCs were characterized by flow cytometry for CD44 (97.7%), CD90 (95.4%), and CD105 (92.3%) markers and were preconditioned with insulin-like growth factor-1 (IGF-1) (50 ng/mL) and fibroblast growth factor-2 (FGF-2) (50 ng/mL) in combination for 1 h in serum-free Iscove's modified Dulbecco's medium. This was followed by hypoxic and high glucose insults to mimic diabetic heart microenvironment and to study the effect of preconditioning. Diabetic MSCs after treatment showed upregulation of IGF-1, FGF-2, Akt, GATA-4, and Nkx 2.5 and downregulation of p16(INK4a), p66(shc), p53, Bax, and Bak. Under hypoxic stress, preconditioned diabetic MSCs showed high superoxide dismutase activity (52.3%) compared with untreated cells (36.9%). This was concomitant with low numbers of annexin-V-positive cells, high in vitro tube-forming ability, and high chemotactic mobility to stromal cell-derived factor-1α after preconditioning in diabetic MSCs. Upregulation of Ang-I and VEGF and downregulation of p16(INK4a) were also observed in preconditioned cells under conditions of high glucose insult. Therefore, preconditioning with IGF-1 and FGF-2 in combination represents a novel strategy to augment MSC function affected by diabetes and holds significance for future strategies to treat diabetic heart failure.

Grafts Enriched with Subamnion-Cord-Lining Mesenchymal Stem Cell Angiogenic Spheroids Induce Post-Ischemic Myocardial Revascularization and Preserve Cardiac Function in Failing Rat Hearts

“…In the present study, CL-MSC were used to assemble angiogenic spheroids that were then coated with HUVEC. These multicellular angiogenic spheroids exhibited increased expression of VEGF dimers, which have been recognized to have enhanced biological function and to increase endothelial cell proliferation, migration and adhesion, thereby being essential for effective angiogenesis [27,28]. Also, VEGF monomers bind to dimers under the effect of mechanical stretching forces or prehypoxic conditions leading to increased angiogenesis [29].…”

The Regenerative Medicine Laboratory: Facilitating Stem Cell Therapy for Equine Disease

“…Examples of these efforts include the use specific bioscaffolds which allow spatial and physical cell manipulation, increase cell survival and promote integration with the host. Furthermore, culture strategies have been evaluated to improve MSC viability by exposing cells to hypoxic conditions [10], specific growth factors [11,12], or a variety of biological agents [13].…”

Estrogen and Insulin Replacement Therapy Modulates the Expression of Insulin‐Like Growth Factor‐I Receptors in the Salivary Glands of Diabetic Mice

“…An experimental study has shown an increased expression of IGF-IR in the salivary glands of diabetic animals. This increase coincided with the period of effective diabetes, indicating a possible imbalance in glandular homeostasis (Caldeira and Cagnon, 2008;Limesand et al, 2009;Jiang and Steinle, 2010;Khan et al, 2010). On the other hand, this intense IGF receptor expression might be associated with an attempt of tissue recovery.…”