Haemopoiesis is sustained by two main cellular components, the haematopoietic cells (HSCs) and the mesenchymal progenitor cells (MPCs). MPCs are multipotent and are the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of HSCs in umbilical cord blood (UCB) is well known, that of MPCs has been not fully evaluated. In this study, we examined the ability of UCB harvests to generate in culture cells with characteristics of MPCs. Results showed that UCB‐derived mononuclear cells, when set in culture, gave rise to adherent cells, which exhibited either an osteoclast‐ or a mesenchymal‐like phenotype. Cells with the osteoclast phenotype were multinucleated, expressed TRAP activity and antigens CD45 and CD51/CD61. In turn, cells with the mesenchymal phenotype displayed a fibroblast‐like morphology and expressed several MPC‐related antigens (SH2, SH3, SH4, ASMA, MAB 1470, CD13, CD29 and CD49e). Our results suggest that preterm, as compared with term, cord blood is richer in mesenchymal progenitors, similar to haematopoietic progenitors.

Within the bone marrow stroma there exists a subset of nonhematopoietic cells referred to as mesenchymal stem or mesenchymal progenitor cells. These cells can be ex vivo expanded and induced, either in vitro or in vivo, to terminally differentiate into osteoblasts, chondrocytes, adipocytes, tenocytes, myotubes, neural cells, and hematopoietic-supporting stroma. The multipotential of these cells, their easy isolation and culture, as well as their high ex vivo expansive potential make these cells an attractive therapeutic tool. In this work we will review the information dealing with the biology of mesenchymal progenitors as it has been revealed mainly by ex vivo studies performed with bone marrow-derived cells. The discussed topics include, among others, characteristics of mesenchymal progenitors, evidence for the existence of a vast repertoire of uncommitted and committed progenitors both in the bone marrow and in mesenchymal tissues, a diagram for their proliferative hierarchy, and comments on mobilization, microenvironment, and clinical use of mesenchymal progenitors. Despite the enormous data available at molecular and cellular levels, it is evident that a number of fundamental questions still need to be resolved before mesenchymal progenitors can be used for safe and effective clinical applications in the context of both cell and gene therapies.

Multipotent mesenchymal stromal cells (MSCs), often labeled mesenchymal stem cells, contribute to tissue regeneration in injured bone and cartilage, as well as in the infarcted heart, brain, and kidney. We hypothesize that MSCs might also contribute to pancreas and kidney regeneration in diabetic individuals. Therefore, in streptozotocin (STZ)-induced type 1 diabetes C57BL/6 mice, we tested whether a single intravenous dose of MSCs led to recovery of pancreatic and renal function and structure. When hyperglycemia, glycosuria, massive beta-pancreatic islets destruction, and mild albuminuria were evident (but still without renal histopathologic changes), mice were randomly separated in 2 groups: 1 received 0.5 x 10(6) MSCs that have been ex vivo expanded (and characterized according to their mesenchymal differentiation potential), and the other group received the vehicle. Within a week, only MSC-treated diabetic mice exhibited significant reduction in their blood glucose levels, reaching nearly euglycemic values a month later. Reversion of hyperglycemia and glycosuria remained for 2 months at least. An increase in morphologically normal beta-pancreatic islets was observed only in MSC-treated diabetic mice. Furthermore, in those animals albuminuria was reduced and glomeruli were histologically normal. On the other side, untreated diabetic mice presented glomerular hyalinosis and mesangial expansion. Thus, MSC administration resulted in beta-pancreatic islets regeneration and prevented renal damage in diabetic animals. Our preclinical results suggest bone marrow-derived MSC transplantation as a cell therapy strategy to treat type 1 diabetes and prevent diabetic nephropathy, its main complication.

The transplantation of mesenchymal stem cells (MSCs) proves to be useful to treat pathologies in which tissue damage is linked to oxidative stress (OS). The aim of our work was to evaluate whether primary human MSCs (hMSCs) can manage OS. For this, in vitro we assessed the following parameters: (1) cell viability of hMSCs exposed to increasing concentrations of reactive oxygen species (ROS; source: hydrogen peroxide), reactive nitrogen species (RNS; source: S-nitroso-N-acetylpenicillamine), or both (ROS and RNS; source: 3-morpholinosydnonimine hydrochloride); (2) intracellular level of reactive species in hMSCs exposed to ROS and RNS; (3) basal gene expression and activity of superoxide dismutases, catalase, and glutathione peroxidase of hMSCs; (4) basal level of total glutathione (GSx) of hMSCs; and (5) cell viability of GSx-depleted hMSCs exposed to ROS and/or RNS. Results showed that hMSCs have a high resistance to OS-induced death, which correlates with low levels of intracellular reactive species, constitutive expression of enzymes required to manage OS, and high levels of GSx. When hMSCs were depleted of GSx they lose their capacity to manage OS. Thus, in vitro hMSCs were able to scavenge ROS and RNS and efficiently manage OS. If this potential is maintained in vivo, hMSCs could also contribute to tissue regeneration, limiting OS-induced tissue damage.

Background/Aim Hypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy. Methods/Results Male C57BL/6 mice were fed with a standardized high-fat diet (obese) or regular diet (normal) for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method) and by hemodynamic parameters (invasive method). Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction), and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study. Conclusions Mice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.