Preconditioning diabetic mesenchymal stem cells with myogenic medium increases their ability to repair diabetic heart

Abstract

IntroductionMesenchymal stem cells (MSCs) have the potential for treatment of diabetic cardiomyopathy; however, the repair capability of MSCs declines with age and disease. MSCs from diabetic animals exhibit impaired survival, proliferation, and differentiation and therefore require a strategy to improve their function. The aim of the study was to develop a preconditioning strategy to augment the ability of MSCs from diabetes patients to repair the diabetic heart.MethodsDiabetes was induced in C57BL/6 mice (6 to 8 weeks) with streptozotocin injections (55 mg/kg) for 5 consecutive days. MSCs isolated from diabetic animals were preconditioned with medium from cardiomyocytes exposed to oxidative stress and high glucose (HG/H-CCM).ResultsGene expression of VEGF, ANG-1, GATA-4, NKx2.5 MEF2c, PCNA, and eNOS was upregulated after preconditioning with HG/H-CCM, as evidenced by reverse transcriptase/polymerase chain reaction (RT-PCR). Concurrently, increased AKT phosphorylation, proliferation, angiogenic ability, and reduced levels of apoptosis were observed in HG/H-CCM-preconditioned diabetic MSCs compared with nontreated controls. HG/H-CCM-preconditioned diabetic-mouse-derived MSCs (dmMSCs) were transplanted in diabetic animals and demonstrated increased homing concomitant with augmented heart function. Gene expression of angiogenic and cardiac markers was significantly upregulated in conjunction with paracrine factors (IGF-1, HGF, SDF-1, FGF-2) and, in addition, reduced fibrosis, apoptosis, and increased angiogenesis was observed in diabetic hearts 4 weeks after transplantation of preconditioned dmMSCs compared with hearts with nontreated diabetic MSCs.ConclusionsPreconditioning with HG/H-CCM enhances survival, proliferation, and the angiogenic ability of dmMSCs, augmenting their ability to improve function in a diabetic heart.

In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments

“…This improved heart-repairing properties of the MSCs after their transplantation into diabetic animal (Khan et al 2013).…”

“…In another study, enhanced expression of pro-angiogenesis growth factors has been reported following cultivation of diabetic donor-derived MSCs in the presence of cardiomyocytes-conditioned medium (Khan et al 2013). This improved heart-repairing properties of the MSCs after their transplantation into diabetic animal (Khan et al 2013).…”

Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential

“…Such strategies include treatment with growth factors, 8,9 cytokines, [10][11][12] hypoxic shock, 13 HDLs, 14 lipopolysaccharide (LPS) 15 or chemical compounds. 16,17 Based on findings from these studies, pre-treatment greatly enhances cell survival and the potential to migrate to damaged or inflamed tissues, thereby markedly improving the efficacy of these cells in the treatment of certain diseases or in tissue repair in an injury-specific fashion. A notable example is that hypoxia preconditioned MSCs dramatically promote tissue repair of myocardial ischemiareperfusion injury, 18 ischemic acute kidney injury 19 and experimental traumatic brain injury.…”

Use of regenerative tissue for urinary diversion

“…Importantly, not all recipients are the same nor is the quality of their tissues. Inherent patient characteristics including age, common comorbidities, such as diabetes and cardiovascular disease, tobacco use, and genetic abnormalities may reduce engineering tissue capacity, introducing variability in TEUD quality and reducing successful implementation [36][37][38][39][40].…”