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Abstract Introduction

Different mesenchymal stromal cells (MSC) have been successfully isolated and expanded in vitro and nowadays they are tested in clinical trials for a wide variety of diseases. Whether all MSC express the same cell surface markers or have a similar secretion profile is still controversial, making it difficult to decide which stromal cell may be better for a particular application.

We isolated human mesenchymal stromal cells from bone marrow (BM), adipose tissue (AT) and Whartons jelly (WJ) and cultured them in fetal bovine serum supplemented media. We evaluated proliferation, in vitro differentiation (osteogenic, adipogenic and chondrogenic potential), expression of cell surface markers and protein secretion using Luminex and ELISA assays.

Cell proliferation was higher for WJ-MSC, followed by AT-MSC. Differences in surface expression markers were observed only for CD54 and CD146. WJ-MSC secreted higher concentrations of chemokines, pro-inflammatory proteins and growth factors. AT-MSC showed a better pro-angiogenic profile and secreted higher amounts of extracellular matrix components and metalloproteinases.

Mesenchymal stromal cells purified from different tissues have different angiogenic, inflammatory and matrix remodeling potential properties. These abilities should be further characterized in order to choose the best protocols for their therapeutic use.

Mesenchymal stromal cells (MSC) are a small population of multipotent progenitor cells present in nearly all human tissues, being mostly found in the perivascular niche [1]. MSC were first isolated from bone marrow [2], but they have been obtained subsequently from a wide variety of fetal and adult tissues: adipose tissue [3], placenta [4], lung [5], umbilical cord [6], synovial membrane [7] and dental pulp [8] among many others.

Regenerative medicine makes use of MSC and of their multipotent properties to promote tissue regeneration. MSC are able to migrate into injured tissues, engraft and differentiate into many cell types, participating thus directly in tissue repair and regeneration [9]. They also secrete paracrine mediators, reducing inflammation and accelerating tissue regeneration by activation of resident stem cells and mobilization of circulating systemic stem cells through chemotactic signaling [10,11]. Clinical trials have already confirmed that use of MSC is safe and effective [12]. Even when MSC express major histocompatibility complex class I, they proved to be safe in allogeneic transplants, also between HLA-incompatible individuals, since they do not elicit alloreactive lymphocyte proliferative responses in vitro, they produce locally immunomodulatory proteins and their expression levels of major histocompatibility complex class II are negligible [13,14].

Studies comparing MSC derived from different tissues are limited to in vitro and pre-clinical studies. Clinical trials are generally focused on safety and efficiency of a therapy using a specific type of MSC, without demonstrating which MSC is the best for each therapy, or even justifying why a specific cell type was believed to be the best option. Basic MSC comparative studies are required to better understand MSC properties and abilities, indicating the most appropriate MSC type for a particular clinical application.

In vitro studies have already shown that MSC from different origins varied when considering differentiation potential: some cells are better for differentiation into osteoblast-like cells [15], while synovium-derived MSC and umbilical cord-derived MSC are better differentiated into chondrocytes than the bone marrow-derived MSC [16,17]. MSC isolated from fetal tissues are superior regarding cardiomyocyte and endothelial cell differentiation when compared to adult tissue-derived MSC [18].

Besides differentiation potential, recent studies have approached other MSC attributes that allowed a deeper understanding of tissue-derived properties. Hsieh and colleagues compared MSC derived from Whartons Jelly and bone marrow regarding their ability to regenerate infarcted myocardia; they described secretome differences that make Whartons Jelly-derived MSC a more angiogenic, neuroprotective and neurogenic option [19]. Naftali-Shani and coworkers carried out a pre-clinical trial of myocardial infarction in rats comparing the effects of human stromal cells obtained from four locations (epicardial fat, pericardial fat, subcutaneous fat and the right atrium) and they showed that hMSCs from epicardial fat and the right atrium secreted the highest amounts of trophic and inflammatory cytokines in vitro, expressed higher amounts of inflammation- and fibrosis-related genes in vitro and impaired heart recovery in vivo[20]. Research studies like these mentioned here are essential for determining the best tissue-derived mesenchymal stromal cell for a particular regenerative therapy strategy.

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