Crosstalk between Stem and Progenitor Cellular Mediators with Special Emphasis on Vasculogenesis.

The cellular components and molecular processes of signaling during vasculogenesis have been investigated for decades. Considerable efforts have been made to unravel regulatory mechanisms of vasculogenesis through crosstalk between vasculogenic playmakers located in the vascular niche, namely hematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem and progenitor cells. Recent studies have increased the knowledge about signaling events within vascular microenvironment that leads to vasculogenesis. Findings from these recent studies indicate the impact of cellular crosstalk through signaling pathways such as vascular endothelial growth factor signaling, wingless and Notch signaling in vasculogenesis and vascular development. In this review, we highlight the signaling signature between stem and progenitor cellular mediators during vasculogenesis. We further focus on hematopoietic stem cell-endothelial progenitor cell crosstalk during vasculogenesis and discuss their potential implications and benefits for therapeutic interventions and regenerative therapy.

Comparison of bacterial biodiversity and enzyme production in three hypersaline lakes; urmia, howz-soltan and aran-bidgol.

This research is a comparative study on the diversity of halophilic bacteria with hydrolytic activities in three significant hypersaline lakes; Urmia in the northwest and Howz-Soltan and Aran-Bidgol in the central desert in Iran. Isolated strains from these saline lakes were found to be halotolerant, moderately and extremely halophilic bacteria. The bacteria in each saline lake were able to produce different hydrolytic enzymes including amylase, protease, lipase, DNase, inulinase, xylanase, carboxy methyl cellulase, pectinase and pullulanase. 188, 302, 91 halophilic strains were isolated from Urmia Lake, Howz-Soltan and Aran-Bidgol playa, respectively. The numbers of Gram-positive strains were more than Gram-negatives, and among Gram-positive bacteria; spore-forming bacilli were most abundant. Due to the unique physico-chemical conditions of the lake environments, the hydrolytic activities of isolated strains were significantly different. For instance, isolated strains from Howz-Soltan playa did not produce pectinase, DNase, amylase, lipase and inulinase, while the isolates from Aran-Bidgol playa had a great ability to produce pectinase and DNase. The strains from Urmia Lake were also good producers of DNase but failed to show any chitinase activity. The diversity of halophilic bacteria from the mentioned three saline lakes was also determined using PCR-amplified 16S rRNA followed by phylogenetic analysis of the partial 16S rRNA sequences.

Macrophages in the pancreas: Villains by circumstances, not necessarily by actions.

INTRODUCTION: Mounting evidence suggest that macrophages play crucial roles in disease and tissue regeneration. However, despite much efforts during the past decade, our knowledge about the extent of macrophages' contribution to adult pancreatic regeneration after injury or during pancreatic disease progression is still limited. Nevertheless, it is generally accepted that some macrophage features that normally would contribute to healing and regeneration may be detrimental in pancreatic cancer. Altogether, the current literature contains conflicting reports on whether macrophages act as friends or foe in these conditions. METHODS AND RESULTS: In this review, we briefly review the origins of tissue resident and infiltrating macrophages and the importance of cellular crosstalking between macrophages and other resident cells in tissue regeneration. The primary objective of this review is to summarize our knowledge of the distinct roles of tissue resident and infiltrating macrophages, the impact of M1 and M2 macrophage phenotypes, and emerging evidence on macrophage crosstalking in pancreatic injury, regeneration, and disease. CONCLUSION: Macrophages are involved with various stages of pancreatic cancer development, pancreatitis, and diabetes. Elucidating their role in these conditions will aid the development of targeted therapeutic treatments.

Mesenchymal Stem and Progenitor Cells in Regeneration: Tissue Specificity and Regenerative Potential.

It has always been an ambitious goal in medicine to repair or replace morbid tissues for regaining the organ functionality. This challenge has recently gained momentum through considerable progress in understanding the biological concept of the regenerative potential of stem cells. Routine therapeutic procedures are about to shift towards the use of biological and molecular armamentarium. The potential use of embryonic stem cells and invention of induced pluripotent stem cells raised hope for clinical regenerative purposes; however, the use of these interventions for regenerative therapy showed its dark side, as many health concerns and ethical issues arose in terms of using these cells in clinical applications. In this regard, adult stem cells climbed up to the top list of regenerative tools and mesenchymal stem cells (MSC) showed promise for regenerative cell therapy with a rather limited level of risk. MSC have been successfully isolated from various human tissues and they have been shown to offer the possibility to establish novel therapeutic interventions for a variety of hard-to-noncurable diseases. There have been many elegant studies investigating the impact of MSC in regenerative medicine. This review provides compact information on the role of stem cells, in particular, MSC in regeneration.

Identification of an effective early signaling signature during neo-vasculogenesis in vivo by ex vivo proteomic profiling.

Therapeutic neo-vasculogenesis in vivo can be achieved by the co-transplantation of human endothelial colony-forming progenitor cells (ECFCs) with mesenchymal stem/progenitor cells (MSPCs). The underlying mechanism is not completely understood thus hampering the development of novel stem cell therapies. We hypothesized that proteomic profiling could be used to retrieve the in vivo signaling signature during the initial phase of human neo-vasculogenesis. ECFCs and MSPCs were therefore either transplanted alone or co-transplanted subcutaneously into immune deficient mice. Early cell signaling, occurring within the first 24 hours in vivo, was analyzed using antibody microarray proteomic profiling. Vessel formation and persistence were verified in parallel transplants for up to 24 weeks. Proteomic analysis revealed significant alteration of regulatory components including caspases, calcium/calmodulin-dependent protein kinase, DNA protein kinase, human ErbB2 receptor-tyrosine kinase as well as mitogen-activated protein kinases. Caspase-4 was selected from array results as one therapeutic candidate for targeting vascular network formation in vitro as well as modulating therapeutic vasculogenesis in vivo. As a proof-of-principle, caspase-4 and general caspase-blocking led to diminished endothelial network formation in vitro and significantly decreased vasculogenesis in vivo. Proteomic profiling ex vivo thus unraveled a signaling signature which can be used for target selection to modulate neo-vasculogenesis in vivo.

Oxygen sensing mesenchymal progenitors promote neo-vasculogenesis in a humanized mouse model in vivo.

Despite insights into the molecular pathways regulating hypoxia-induced gene expression, it is not known which cell types accomplish oxygen sensing during neo-vasculogenesis. We have developed a humanized mouse model of endothelial and mesenchymal progenitor co-transplantation to delineate the cellular compartments responsible for hypoxia response during vasculogenesis. Mesenchymal stem/progenitor cells (MSPCs) accumulated nuclear hypoxia-inducible transcription factor (HIF)-1α earlier and more sensitively than endothelial colony forming progenitor cells (ECFCs) in vitro and in vivo. Hypoxic ECFCs showed reduced function in vitro and underwent apoptosis within 24h in vivo when used without MSPCs. Surprisingly, only in MSPCs did pharmacologic or genetic inhibition of HIF-1α abrogate neo-vasculogenesis. HIF deletion in ECFCs caused no effect. ECFCs could be rescued from hypoxia-induced apoptosis by HIF-competent MSPCs resulting in the formation of patent perfused human vessels. Several angiogenic factors need to act in concert to partially substitute mesenchymal HIF-deficiency. Results demonstrate that ECFCs require HIF-competent vessel wall progenitors to initiate vasculogenesis in vivo and to bypass hypoxia-induced apoptosis. We describe a novel mechanistic role of MSPCs as oxygen sensors promoting vasculogenesis thus underscoring their importance for the development of advanced cellular therapies.