REVIEW UC blood-derived mesenchymal stromal cells: an overview A Flynn, F Barry and T O’Brien Regenerative Medicine Institute (REMEDI), National Centre for Biomedical Engineering Science (NCBES), National University of Ireland (NUI), Galway, Ireland The UC is a readily available source of blood that may be used for analysis and treatment. Some authors suggest that within the UC blood (UCB) are cells with potential for differentiation down mesenchymal lineages. Isolation and characterization of these cells has been accomplished in some centers. Differentiation of these cells down multiple lineages has been documented. Surface marker expression and gene expression profiling has been performed, and mesenchymal stromal cells (MSC) from BM and adipose tissue have been compared with those derived from UCB. The use of UCB-derived stem cells has been investigated in pre-clinical studies. As this field is rapidly advancing, this review summarizes the current state of our knowledge of MSC derived from UCB. Keywords characterization, cytokine, differentiation, genomic, isolation, mesench- ymal stromal cells, pre-clinical, umbilical cord blood. Introduction The human UC is an essential organ. This tubular structure allows the exchange of oxygen and nutrients between the developing embryo and the placenta, features necessary for in utero viability. It develops from, and contains remnants of, the embryonic yolk sac and allantois. It contains two arteries and a single vein, which are surrounded by a gelatinous substance called Wharton’s jelly [1]. Within the umbilical vein are both mature and progenitor cells of the fetus. UC blood (UCB) cells are derived from the trophoblast and other non-embryonic tissues and, while they are not considered embryonic cells, the young chronologic age of these progenitor cells is considered a strong advantage over similar cells from different sources [2,3]. The umbilical vein is a readily available potential source of progenitor cells that may be used for clinical and therapeutic purposes. A progenitor cell that has been identified as being of great therapeutic potential is the mesenchymal stromal cell (MSC) [4]. While significant volumes of work have been published demonstrating the presence of MSC within BM, the relative invasiveness of their collection has led some to investigate their presence within other organs [58]. There is evidence that MSC may be isolated from the umbilical vein and adipose tissue as well as BM [6,9]. Furthermore, cells that have MSC-like properties (the ability to differentiate into cells of a mesenchymal lineage) have been isolated from a number of other sources [10,11]. MSC comprise a rare population of multipotent pro- genitor cells that are capable of supporting hematopoiesis, self-renewing and differentiating into at least three lineages: osteogenic, adipogenic and chondrogenic [12]. They are present within the BM and are readily expandable in vitro [13]. From a typical BM aspirate, it is estimated that the proportion of mononuclear cells that are MSC is in the region of 0.001 0.01% [12]. Induction of differentiation is now well described [2,5 9,1222]. These cells do not express typical hematopoietic lineage markers and they are generally identified through a combination of poorly defined physical, phenotypic and functional properties [23]. Their pharmacologic importance is related to four points: MSC secrete biologically important molecules; express specific receptors; can be genetically manipulated; and are susceptible to molecules that modify their natural behavior. MSC thus have impressive potential for thera- peutic and clinical applications. Correspondence to: Timothy O’Brien, Director, REMEDI, NCBES, NUI, Galway, Ireland. E-mail: timothy.obrien@nuigalway.ie. Cytotherapy (2007) Vol. 9, No. 8, 717726 – 2007 ISCT DOI: 10.1080/14653240701584578