Attachment and Differentiation of Human Umbilical Cord Stem Cells on to the Tooth Root Surface with and without the Use of Fibroblast Growth Factor-An In Vitro Study

BACKGROUND AND OBJECTIVES: The purpose of this first of its kind study was to analyse the growth, development and attachment of cultured human umbilical cord stem cells alone or supplemented with basic Fibroblast Growth Factor (bFGF) on both healthy and periodontally diseased tooth surfaces in vitro. METHODS: Four groups of 12 root surface scaffolds each were classified as Group I- healthy root surfaces; Group II- periodontally diseased; Group III- Healthy with bFGF and Group IV- periodontally diseased root with bFGF. bFGF was applied in the concentration of 8 ng/ml on to the surface followed by incubation of cultured human umbilical cord stem cells (hUCMSCs) on the scaffolds. Scanning electron microscopy observations were made on 14th and 21st days to assess the proliferation and morphology of cells attached on the tooth surface. RESULTS: Cultured hUCMSCs demonstrated adhesion to tooth root scaffold. All the groups showed a significant increase in the number of cell attachment from 14th day to 21st day. The groups with bFGF showed a significant increase in attachment of cells when compared to the groups without bFGF. The cells showed an increase in number of flat cells from 14th day to 21st day in all the groups indicating an increased maturity of cells. Periodontally diseased groups had less maturity of cells than healthy groups. The groups supplemented with bFGF, had more mature cells than the groups without bFGF. CONCLUSIONS: hUCMSCs have the propensity to differentiate into cells that have the capacity to bind to root surfaces. hUCMSCs incubated with bFGF showed better proliferation and attachment to tooth root surfaces. The role of hUCMSCs can be further explored for periodontal regeneration.

Overexpression of hsa-miR-125b during osteoblastic differentiation does not influence levels of Runx2, osteopontin, and ALPL gene expression

Multipotent mesenchymal stromal cells (MSCs) were first isolated from bone marrow and then from various adult tissues including placenta, cord blood, deciduous teeth, and amniotic fluid. MSCs are defined or characterized by their ability to adhere to plastic, to express specific surface antigens, and to differentiate into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Although the molecular mechanisms that control MSC proliferation and differentiation are not well understood, the involvement of microRNAs has been reported. In the present study, we investigated the role of miR-125b during osteoblastic differentiation in humans. We found that miR-125b increased during osteoblastic differentiation, as well as Runx2 and ALPL genes. To study whether the gain or loss of miR-125b function influenced osteoblastic differentiation, we transfected MSCs with pre-miR-125b or anti-miR-125b and cultured the transfected cells in an osteoblastic differentiation medium. After transfection, no change was observed in osteoblastic differentiation, and Runx2, OPN, and ALPL gene expression were not changed. These results suggest that the gain or loss of miR-125b function does not influence levels of Runx2, OPN, and ALPL during osteoblastic differentiation.

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC) are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal) or high-fat diet (obese). Obese animals received the vehicle (obese), a single dose (obese + 1x MSC) or three doses (obese + 3x MSC) of 0.5x10(6) syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy.

MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN), a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs). The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.