Angiogenic and anti-inflammatory properties of micro-fragmented fat tissue and its derived mesenchymal stromal cells.

BACKGROUND: Adipose-derived mesenchymal stromal cells (Ad-MSCs) are a promising tool for advanced cell-based therapies. They are routinely obtained enzymatically from fat lipoaspirate (LP) as SVF, and may undergo prolonged ex vivo expansion, with significant senescence and decline in multipotency. Besides, these techniques have complex regulatory issues, thus incurring in the compelling requirements of GMP guidelines. Hence, availability of a minimally manipulated, autologous adipose tissue would have remarkable biomedical and clinical relevance. For this reason, a new device, named Lipogems® (LG), has been developed. This ready-to-use adipose tissue cell derivate has been shown to have in vivo efficacy upon transplantation for ischemic and inflammatory diseases. To broaden our knowledge, we here investigated the angiogenic and anti-inflammatory properties of LG and its derived MSC (LG-MSCs) population. METHODS: Human LG samples and their LG-MSCs were analyzed by immunohistochemistry for pericyte, endothelial and mesenchymal stromal cell marker expression. Angiogenesis was investigated testing the conditioned media (CM) of LG (LG-CM) and LG-MSCs (LG-MSCs-CM) on cultured endothelial cells (HUVECs), evaluating proliferation, cord formation, and the expression of the adhesion molecules (AM) VCAM-1 and ICAM-1. The macrophage cell line U937 was used to evaluate the anti-inflammatory properties, such as migration, adhesion on HUVECs, and release of RANTES and MCP-1. RESULTS: Our results indicate that LG contained a very high number of mesenchymal cells expressing NG2 and CD146 (both pericyte markers) together with an abundant microvascular endothelial cell (mEC) population. Substantially, both LG-CM and LG-MSC-CM increased cord formation, inhibited endothelial ICAM-1 and VCAM-1 expression following TNFα stimulation, and slightly improved HUVEC proliferation. The addition of LG-CM and LG-MSC-CM strongly inhibited U937 migration upon stimulation with the chemokine MCP-1, reduced their adhesion on HUVECs and significantly suppressed the release of RANTES and MCP-1. CONCLUSIONS: Our data indicate that LG micro-fragmented adipose tissue retains either per se, or in its embedded MSCs content, the capacity to induce vascular stabilization and to inhibit several macrophage functions involved in inflammation

Drug-releasing mesenchymal cells strongly suppress B16 lung metastasis in a syngeneic murine model

Mesenchymal stromal cells (MSCs) are considered an important therapeutic tool in cancer therapy. They possess intrinsic therapeutic potential and can also be in vitro manipulated and engineered to produce therapeutic molecules that can be delivered to the site of diseases, through their capacity to home pathological tissues. We have recently demonstrated that MSCs, upon in vitro priming with anti-cancer drug, become drug-releasing mesenchymal cells (Dr-MCs) able to strongly inhibit cancer cells growth

3D culture of isolated cells: a fast and efficient method for optimizing their histochemical and immunocytochemical analyses

The rapid development of three-dimensional (3D) culture systems and engineered cell-based tissue models gave rise to an increasing need of new techniques, allowing the microscopic observation of cell behavior/morphology in tissue-like structures, as clearly signalled by several authors during the last decennium. With samples consisting of small aggregates of isolated cells grown in suspension, it is often difficult to produce an optimal embedded preparation that can be further successfully processed for classical histochemical investigations. In this work, we describe a new, easy to use, efficient method that enables to embed an enriched "preparation" of isolated cells/small 3D cell aggregates, without any cell stress or damage. As for after tissue-embedding procedures, the cellular blocks can be further suitably processed for efficient histochemical as well as immunohistochemical analyses, rendering more informative-and attractive-studies onto 3D cell-based culture of neo-tissues. Microsc. Res. Tech., 2015. © 2015 Wiley Periodicals, Inc

Normal, hyperplastic and neoplastic epithelium of mammary gland: comparative evaluation by some lectins.

ATTI DEL XXII CONGRESSO NAZIONALE DELLA SOCIETÀ ITALIANA DI ISTOCHIMIC