We have undertaken an in-depth transcriptome analysis of adipogenesis in human adipose-derived stromal cells (ASCs) induced to differentiate into adipocytes in vitro. Gene expression was assessed on days 1, 7, 14 and 21 post-induction and genes differentially expressed numbered 128, 218, 253 and 240 respectively. Up-regulated genes were associated with blood vessel development, leukocyte migration, as well as tumor growth, invasion and metastasis. They also shared common pathways with certain obesity-related pathophysiological conditions. Down-regulated genes were enriched for immune response processes. KLF15, LMO3, FOXO1 and ZBTB16 transcription factors were up-regulated throughout the differentiation process. CEBPA, PPARG, ZNF117, MLXIPL, MMP3 and RORB were up-regulated only on days 14 and 21, which coincide with the maturation of adipocytes and could possibly serve as candidates for controlling fat accumulation and the size of mature adipocytes. In summary, we have identified genes that were up-regulated only on days 1 and 7 or days 14 and 21 that could serve as potential early and late-stage differentiation markers.

The use of stem cells in regenerative medicine, including tissue engineering and transplantation, has generated a great deal of enthusiasm. Mesenchymal stromal/stem cells (MSCs) can be isolated from various tissues, most commonly, bone marrow but more recently adipose tissue, dental pulp, and Whartons jelly, to name a few. MSCs display varying phenotypic profiles and osteogenic differentiating capacity depending and their site of origin. MSCs have been successfully differentiated into osteoblasts both in vitro an in vivo but discrepancies exist when the two are compared: what happens in vitro does not necessarily happen in vivo, and it is therefore important to understand why these differences occur. The osteogenic process is a complex network of transcription factors, stimulators, inhibitors, proteins, etc., and in vivo experiments are helpful in evaluating the various aspects of this osteogenic process without distractions and confounding variables. With that in mind, the results of in vitro experiments need to be carefully considered and interpreted with caution as they do not perfectly replicate the conditions found within living organisms. This is where in vivo experiments help us better understand interactions that might occur in the osteogenic process that cannot be replicated in vitro. Potentially, these differences could also be exploited to develop an optimal MSC cell therapeutic product that can be used for bone disorders. There are many bone disorders, most of which cause a great deal of discomfort. Clinically acceptable protocols could be developed in which MSCs are used to aid in bone regeneration providing relief for patients with chronic pain. The aim of this review is to examine the differences between studies conducted in vitro and in vivo with regard to the osteogenic process to better define the gaps in current osteogenic research. By better understanding osteogenic differentiation, we can better define treatment strategies for various bone disorders.

Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells, HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias.

The effects that the Streptococcus pneumoniae–derived, proinflammatory toxin, pneumolysin (8.37 and 41.75 ng/mL), has on the production of interleuki

Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an early negative regulator of adipogenic differentiation. In this review, we briefly discuss the adipogenic differentiation potential of MSCs derived from two different sources, namely adipose-derived stromal/stem cells (ASCs) and Wharton’s Jelly derived stromal/stem cells (WJSCs). We then discuss the function and suggested mechanisms of action of Pref-1 in regulating adipogenesis, as well as current findings regarding Pref-1’s role in human adipogenesis.